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  • 1.
    Agnafors, 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.
    Barmark, Mimmi
    Lund Univ, Sweden.
    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.
    Correction: Mental health and academic performance: a study on selection and causation effects from childhood to early adulthood (vol 56, pg 857, 2021)2023In: Social Psychiatry and Psychiatric Epidemiology, ISSN 0933-7954, E-ISSN 1433-9285Article in journal (Other academic)
  • 2.
    Agnafors, 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.
    Barmark, Mimmi
    Lund Univ, Sweden.
    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.
    Mental health and academic performance: a study on selection and causation effects from childhood to early adulthood2021In: Social Psychiatry and Psychiatric Epidemiology, ISSN 0933-7954, E-ISSN 1433-9285, Vol. 56, no 5, p. 857-866Article in journal (Refereed)
    Abstract [en]

    Purpose

    An inverse relationship between mental health problems and academic achievement is a well-known phenomenon in the scientific literature. However, how and when this association develops is not fully understood and there is a lack of longitudinal, population-based studies on young children. Early intervention is important if associations are to be found already during childhood. The aim of the present study was to investigate the development of the association between mental health and academic performance during different developmental periods of childhood and adolescence.

    Methods

    Data from a longitudinal birth cohort study of 1700 children were used. Child mental health was assessed through mother’s reports at age 3, and self-reports at age 12 and 20. Academic performance was assessed through teacher reports on educational results at age 12 and final grades from compulsory school (age 15–16) and upper secondary school (age 18–19). The association between mental health and academic performance was assessed through regression models.

    Results

    The results indicate that social selection mechanisms are present in all three periods studied. Behavioral and emotional problems at age 3 were associated with performing below grade at age 12. Similarly, mental health problems at age 12 were associated with lack of complete final grades from compulsory school and non-eligibility to higher education. Academic performance at ages 15 and 19 did not increase the risk for mental health problems at age 20.

    Conclusion

    Mental health problems in early childhood and adolescence increase the risk for poor academic performance, indicating the need for awareness and treatment to provide fair opportunities to education.

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  • 3.
    Agnafors, 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.
    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.
    Ekselius, Lisa
    Uppsala Univ, Sweden.
    Svedin, Carl Goran
    Ersta Skondal Bracke Univ Coll, Sweden.
    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.
    Maternal temperament and character: associations to child behavior at the age of 3 years2021In: Child and Adolescent Psychiatry and Mental Health, E-ISSN 1753-2000, Vol. 15, no 1, article id 23Article in journal (Refereed)
    Abstract [en]

    Background The influence of maternal temperament on child behavior, and whether maternal temperament impact boys and girls differently is not thoroughly studied. The aim was to investigate the impact of maternal temperament and character on child externalizing and internalizing problems at age 3. Methods A birth-cohort of 1723 mothers and their children were followed from birth to age 3. At the childs age of 3 months, the mothers filled out standardized instruments on their temperament and character using the Temperament and Character Inventory (TCI) and depressive symptoms using the Edinburgh Postnatal Depression Scale (EPDS). At the childs age of 3 years, the mothers reported on child behavior using the Child Behaviour Checklist (CBCL). Results Maternal temperamental trait novelty seeking was positively associated with externalizing problems in the total population and in girls. Harm avoidance was positively associated with externalizing problems in the total population and in boys, and with internalizing problems in the total population and boys and girls respectively. Maternal character traits of self-directedness and cooperativeness were negatively associated with both externalizing and internalizing problems in the total population and in boys and girls respectively. Conclusions Maternal character traits were more influential on child behavior than were temperamental traits, and thus the opportunities for intervention targeted at parental support are good. Maternal mental health and socioeconomic aspects also increased the risk for child behavior problems, indicating the need for recognition and support in clinical settings.

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  • 4.
    Agnafors, 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. Sodra Alvsborgs Hosp, Sweden.
    Kjellstrom, Anna Norman
    Reg Vastra Gotaland, Sweden.
    Bjork, Marcus Praetorius
    Reg Vastra Gotaland, Sweden; Univ Gothenburg, Sweden.
    Rusner, Marie
    Sodra Alvsborgs Hosp, Sweden; Univ Gothenburg, Sweden.
    Torgerson, Jarl
    Sahlgrens Univ Hosp, Sweden.
    Health care utilization in children and adolescents with psychiatric disorders2023In: Acta Psychiatrica Scandinavica, ISSN 0001-690X, E-ISSN 1600-0447, Vol. 148, no 4, p. 327-337Article in journal (Refereed)
    Abstract [en]

    Objective: Mental illness is increasing among young people and likewise the request for health care services. At the same time, somatic comorbidity is common in children and adolescents with psychiatric disorders. There is a lack of studies on health care use in children and adolescents, and the hypothesis was that children and adolescents with psychiatric disorders use more primary-, and specialized somatic health care compared to children without psychiatric disorders. Methods: In this retrospective population-based register study, all individuals aged 3-17 years living in Vastra Gotaland region in Sweden in 2017 were included (n = 298,877). Linear and Poisson regression were used to compare health care use during 2016-2018 between children with and without psychiatric diagnoses, controlling for age and gender. The results were reported as unstandardised beta coefficient (beta) and adjusted prevalence ratio (aPR) respectively. Results: Having a psychiatric diagnosis was associated with more primary care visits (beta 2.35, 95% CI 2.30-2.40). This applied to most diagnoses investigated. Girls had more primary care visits than boys. Likewise, individuals with psychiatric diagnoses had more specialized somatic outpatient care (beta 1.70, 95% CI 1.67-1.73), both planned and unplanned (beta 1.23, 95% CI 1.21-1.25; beta 0.18, 95% CI 0.17-0.19). Somatic inpatient care was more common in those having a psychiatric diagnosis (aPR 1.65, 95% CI 1.58-1.72), with the diagnoses of psychosis and substance use exerting the greatest risk. Conclusions: Psychiatric diagnoses were associated with increased primary-, somatic outpatient- as well as somatic inpatient care. Increased awareness of comorbidity and easy access to relevant health care could be beneficial for patients and caregivers. The results call for a review of current health care systems with distinct division between medical disciplines and levels of health care.

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  • 5.
    Agnafors, 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. Sodra Alvsborgs Hosp, Sweden.
    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 Goran
    Marie Cederschiold Univ, 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.
    Symptoms of depression and internalizing problems in early adulthood - associated factors from birth to adolescence2023In: Nordic Journal of Psychiatry, ISSN 0803-9488, E-ISSN 1502-4725, Vol. 77, no 8, p. 799-810Article in journal (Refereed)
    Abstract [en]

    PurposeEven though the mechanisms behind the development of depression and internalizing problems remains unknown, many different factors have been shown to increase the risk. Longitudinal studies enable the investigation of exposure during different developmental periods during childhood. This study aims to examine factors associated with depressive and internalizing problems at age 20 in terms of sociodemographic factors, previous mental health problems and stressful life events during childhood, adolescence, and early adulthood.MethodsA birth cohort of 1723 children were followed to age 20. At the 20-year follow-up, n = 731 (44%) participated. Standardized instruments were filled out at baseline and the 3-,12- and 20-year follow-ups.ResultsDepressive problems at age 20 were associated with female gender, experience of interpersonal life events reported at age 20, bullying victimization and reports on paternal mental health problems. Participants with depressive problems were also less likely to have experienced adolescence as happy and to report that their father had been a good father. Internalizing problems at age 20 were, in addition, associated with internalizing problems at age 12 and reports on maternal mental health problems. Internalizing problems were associated with a lower likelihood of experiencing adolescence as happy in the final model.ConclusionRecent events (i.e. interpersonal life events and bullying) seemed to be the most influential factors on the development of internalizing and depressive problems. Internalizing problems during childhood increased the risk for internalizing problems in early adulthood, emphasizing the importance of early intervention. Fewer factors were found to increase the risk for depressive problems compared to internalizing problems.

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  • 6.
    Agnafors, 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. Sodra Alvsborgs Hosp, Sweden.
    Torgerson, Jarl
    Sahlgrens Univ Hosp, Sweden.
    Rusner, Marie
    Sodra Alvsborgs Hosp, Sweden; Univ Gothenburg, Sweden.
    Kjellstrom, Anna Norman
    Head Off, Sweden.
    Injuries in children and adolescents with psychiatric disorders2020In: BMC Public Health, E-ISSN 1471-2458, Vol. 20, no 1, article id 1273Article in journal (Refereed)
    Abstract [en]

    Background Unintentional injuries are a leading cause of morbidity and mortality in children of all ages. Prevention strategies require knowledge of risk factors, and behavior and psychiatric disorders have been suggested to influence the risk of injury during childhood. While externalizing disorders have been found to increase the risk for injuries, results are mixed regarding internalizing disorders, such as affective and anxiety conditions, and Autism Spectrum Disorders (ASD). There is a need for large scale studies relying on robust data sources. The aim of the present study was to examine the association between psychiatric disorders and injuries requiring medical attention, in a large population-based cohort of 350,000 children and adolescents in Sweden. Methods Data were obtained from the regional health care database Vega. Psychiatric diagnoses and injury diagnoses obtained during 2014-2018 for individuals aged 0-17 years in 2016 were extracted. Descriptive statistics were used to examine differences in 5-year injury prevalence between children with and without different psychiatric diagnoses. Logistic regression was used in age-stratified models to test the association between psychiatric diagnoses and injuries requiring medical attention. Results The results show an increased risk for concurrent injuries in general, but the patterns vary by age and psychiatric disorder. Externalizing disorders and anxiety conditions were associated with concurrent injuries, while individuals with ASD had a lower risk for most injuries included. Affective disorders were associated with an increased risk for wounds, concussion, complications and poisoning, while the risk for fractures was decreased. Self-inflicted injury was more common in all psychiatric conditions investigated during adolescence, except for ASD. Children and adolescents with many types of psychiatric disorders were also at increased risk for a concurrent maltreatment diagnosis. Conclusions A general pattern of increased risk for concurrent injuries in children and adolescents with most psychiatric diagnoses was found, but the associations vary by age and type of psychiatric disorder. The results add to the literature on risk factors for injuries in children and adolescents, supporting diagnosis specific patterns. Several psychiatric diagnoses were associated with a marked increase in injury risk, indicating a high burden of disease for affected individuals.

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  • 7.
    Ahlbeck, Lars
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Allergy Center.
    Ahlberg, Emelie
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences.
    Björkander, Janne
    Acad Hlth & Care, Sweden.
    Aldén, Caroline
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences.
    Papapavlou, Georgia
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences.
    Palmberg, Laura
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences.
    Nyström Kronander, Ulla
    Region Östergötland, Medicine Center, Allergy Center.
    Retsas, Pavlos
    Region Östergötland, Medicine Center, Allergy Center.
    Nordenfelt, Patrik
    Cty Hosp Ryhov, Sweden.
    Togö, Totte
    Region Östergötland, Medicine Center, Allergy Center.
    Johansen, Pål
    Univ Zurich, Switzerland.
    Rolander, Bo
    Acad Hlth & Care, Sweden.
    Duchén, Karel
    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, Medicine Center, Allergy Center. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Jenmalm, Maria
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences.
    Intralymphatic immunotherapy with one or two allergens renders similar clinical response in patients with allergic rhinitis due to birch and grass pollen2022In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 52, no 6, p. 747-759Article in journal (Refereed)
    Abstract [en]

    Introduction

    There is a need for a fast, efficient and safe way to induce tolerance in patients with severe allergic rhinitis. Intralymphatic immune therapy has been shown to be effective.

    Methods

    Patients with severe birch and timothy allergy were randomized and received three doses of 0.1 ml of birch and 5-grass allergen extracts (10,000 SQ units/ml, ALK-Abello), or birch and placebo or 5-grass and placebo by ultrasound-guided injections into inguinal lymph nodes at monthly intervals. Rhinoconjunctivitis total symptom score, medication score and rhinoconjunctivitis quality of life questionnaire were evaluated before treatment and after each birch and grass pollen season during three subsequent years. Circulating proportions of T helper subsets and allergen-induced cytokine and chemokine production were analysed by flow cytometry and Luminex.

    Results

    The three groups reported fewer symptoms, lower use of medication and improved quality of life during the birch and grass pollen seasons each year after treatment at an almost similar rate independently of treatment with one or two allergens. Mild local pain was the most common adverse event. IgE levels to birch decreased, whereas birch-induced IL-10 secretion increased in all three groups. IgG4 levels to birch and timothy and skin prick test reactivity remained mainly unchanged. Conjunctival challenge tests with timothy extract showed a higher threshold for allergen. In all three groups, regulatory T cell frequencies were increased 3 years after treatment.

    Conclusions

    Intralymphatic immunotherapy with one or two allergens in patients with grass and birch pollen allergy was safe, effective and may be associated with bystander immune modulatory responses.

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  • 8.
    Ahlbeck, Lars
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Allergy Center.
    Ahlberg, Emelie
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences.
    Stuivers, Linn
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences.
    Bjorkander, Janne
    Futurum, Sweden.
    Nyström Kronander, Ulla
    Region Östergötland, Medicine Center, Allergy Center.
    Retsas, Pavlos
    Linköping University, Department of Biomedical and Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in East Östergötland, Department of Internal Medicine in Norrköping.
    Govindaraj, Dhanapal
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences.
    Jenmalm, Maria
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences.
    Duchén, Karel
    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, Medicine Center, Allergy Center.
    Intralymphatic immunotherapy with birch and grass pollen extracts. A randomized double-blind placebo-controlled clinical trial2023In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 53, no 8, p. 809-820Article in journal (Refereed)
    Abstract [en]

    IntroductionThere is a need to evaluate the safety and efficacy of intralymphatic immunotherapy (ILIT) for inducing tolerance in patients with allergic rhinitis. MethodsThirty-seven patients with seasonal allergic symptoms to birch and grass pollen and skin prick test >3 mm and/or IgE to birch and timothy >0.35 kU/L were randomized to either ILIT, with three doses of 0.1 mL of birch pollen and 5-grass pollen allergen extracts on aluminium hydroxide (10,000 SQ-U/ml; ALK-Abello) or placebo using ultrasound-guided intralymphatic injections at monthly intervals. Daily combined symptom medical score and rhinoconjunctivitis total symptom score were recorded during the peak pollen seasons the year before and after treatment. Rhinoconjunctivitis total symptom score, medication score and rhinoconjunctivitis quality of life questionnaire were recorded annually starting 2 years after treatment. Circulating proportions of T helper cell subsets and allergen-induced cytokine and chemokine production were analysed using flow cytometry and ELISA. ResultsThere were no differences between the groups related to daily combined symptom medical score the year before and after treatment. Two years after ILIT (after unblinding), the actively treated group reported significantly fewer symptoms, lower medication use and improved quality of life than did the placebo group. After the pollen seasons the year after ILIT, T regulatory cell frequencies and grass-induced IFN-gamma levels increased only in the actively treated group. ConclusionIn this randomized controlled trial, ILIT with birch and grass pollen extract was safe and accompanied by immunological changes. Further studies are required to confirm or refute the efficacy of the treatment.

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  • 9.
    Ahlberg, Emelie
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences.
    Martí Generó, Magalí Martí
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences.
    Govindaraj, Dhanapal
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences.
    Severin, Elisabet
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences.
    Duchén, Karel
    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, Medicine Center, Allergy Center.
    Jenmalm, Maria
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences.
    Tingö, Lina
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Orebro Univ, Sweden.
    Immune-related microRNAs in breast milk and their relation to regulatory T cells in breastfed children2023In: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 34, no 4, article id e13952Article in journal (Refereed)
    Abstract [en]

    BackgroundThe immunomodulatory capacity of breast milk may partially be mediated by microRNAs (miRNA), small RNA molecules that regulate gene expression on a post-transcriptional level and are hypothesized to be involved in modulation of immunological pathways. Here, we evaluate the expression of immune-related miRNAs in breast milk after pre- and postnatal supplementation with Limosilactobacillus reuteri and omega-3 (omega-3) polyunsaturated fatty acids (PUFAs), and the association to infant regulatory T cell (Treg) frequencies. MethodsOne-hundred and twenty women included in a double-blind, randomized, placebo-controlled allergy intervention trial received L. reuteri and/or omega-3 PUFAs daily from gestational week 20. Using Taqman qPCR, 24 miRNAs were analyzed from breast milk obtained at birth (colostrum) and after 3 months (mature milk) of lactation. The proportion of activated and resting Treg cells were analyzed in infant blood using flow cytometry at 6, 12, and 24 months. ResultsRelative expression changed significantly over the lactation period for most of the miRNAs; however, the expression was not significantly influenced by any of the supplements. Colostrum miR-181a-3p correlated with resting Treg cell frequencies at 6 months. Colostrum miR-148a-3p and let-7d-3p correlated with the frequencies of activated Treg cells at 24 months, as did mature milk miR-181a-3p and miR-181c-3p. ConclusionMaternal supplementation with L. reuteri and omega-3 PUFAs did not significantly affect the relative miRNA expression in breast milk. Interestingly, some of the miRNAs correlate with Treg subpopulations in the breastfed children, supporting the hypothesis that breast milk miRNAs could be important in infant immune regulation. Trial registrationClinicalTrials.gov-ID: NCT01542970.

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  • 10.
    Ahmadi, Shilan Seyed
    et al.
    Univ Gothenburg, Sweden; Sahlgrens Univ Hosp, Sweden; Uddevalla Cent Hosp, Sweden.
    Pivodic, Aldina
    Stat Konsultgrp, Sweden; Univ Gothenburg, Sweden.
    Svensson, Ann-Marie
    Ctr Registers Reg Vastra Gotaland, Sweden.
    Wedel, Hans
    Univ Gothenburg, Sweden.
    Rathsman, Björn
    Sachs Children & Youth Hosp, Sweden.
    Nyström, Thomas
    Karolinska Inst, Sweden.
    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.
    Lind, Marcus
    Univ Gothenburg, Sweden; Sahlgrens Univ Hosp, Sweden; NU Hosp Grp, Sweden.
    Risk factors for nephropathy in persons with type 1 diabetes: a population-based study2022In: Acta Diabetologica, ISSN 0940-5429, E-ISSN 1432-5233, Vol. 59, p. 761-772Article in journal (Refereed)
    Abstract [en]

    Aims Albuminuria is strongly associated with risk of renal dysfunction, cardiovascular disease and mortality. However, clinical guidelines diverge, and evidence is sparse on what risk factor levels regarding blood pressure, blood lipids and BMI are needed to prevent albuminuria in adolescents and young adults with type 1 diabetes. Methods A total of 9347 children and adults with type 1 diabetes [mean age 15.3 years and mean diabetes duration 1.4 years at start of follow-up] from The Swedish National Diabetes Registry were followed from first registration until end of 2017. Levels for risk factors for a risk increase in nephropathy were evaluated, and the gradient of risk per 1 SD (standard deviation) was estimated to compare the impact of each risk factor. Results During the follow-up period, 8610 (92.1%) remained normoalbuminuric, 737 (7.9%) individuals developed micro- or macroalbuminuria at any time period of whom 132 (17.9% of 737) individuals developed macroalbuminuria. Blood pressure >= 140/80 mmHg was associated with increased risk of albuminuria (p <= 0.0001), as were triglycerides >= 1.0 mmol/L (p = 0.039), total cholesterol >= 5.0 mmol/L (p = 0.0003), HDL < 1.0 mmol/L (p = 0.013), LDL 3.5- < 4.0 mmol/L (p = 0.020), and BMI >= 30 kg/m(2) (p = 0.033). HbA1c was the strongest risk factor for any albuminuria estimated by the measure gradient of risk per 1 SD, followed by diastolic blood pressure, triglycerides, systolic blood pressure, cholesterol and LDL. In patients with HbA1c > 65 mmol/mol (> 8.1%), blood pressure > 140/70 mmHg was associated with increased risk of albuminuria. Conclusions Preventing renal complications in adolescents and young adults with type 1 diabetes need avoidance at relatively high levels of blood pressure, blood lipids and BMI, whereas very tight control is not associated with further risk reduction. For patients with long-term poor glycaemic control, stricter blood pressure control is advocated.

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  • 11.
    Albanese-ONeill, Anastasia
    et al.
    Univ Florida, FL USA.
    Grimsmann, Julia M.
    Univ Ulm, Germany; German Ctr Diabet Res DZD, Germany.
    Svensson, Ann-Marie
    Ctr Registers Reg Vastra Gotaland, Sweden; Univ Gothenburg, Sweden.
    Miller, Kellee M.
    Jaeb Ctr Hlth Res, FL USA.
    Raile, Klemens
    Charite Univ Med Berlin, Germany.
    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.
    Calhoun, Peter
    Jaeb Ctr Hlth Res, FL USA.
    Biesenbach, Beate
    Kepler Univ, Austria.
    Eeg-Olofsson, Katarina
    Univ Gothenburg, Sweden.
    Holl, Reinhard W.
    Univ Ulm, Germany; German Ctr Diabet Res DZD, Germany.
    Maahs, David M.
    Stanford Diabet Res Ctr, CA USA; Stanford Univ, CA USA.
    Hanas, Ragnar
    NU Hosp Grp, Sweden; Univ Gothenburg, Sweden.
    Changes in HbA1c Between 2011 and 2017 in Germany/Austria, Sweden, and the United States: A Lifespan Perspective2022In: Diabetes Technology & Therapeutics, ISSN 1520-9156, E-ISSN 1557-8593, Vol. 24, no 1, p. 32-41Article in journal (Refereed)
    Abstract [en]

    Aims: This study assessed hemoglobin A1c (HbA1c) across the lifespan in people with type 1 diabetes (T1D) in Germany/Austria, Sweden, and the United States between 2011 and 2017 to ascertain temporal and age-related trends. Methods: Data from the Diabetes-Patienten-Verlaufsdokumentation (DPV) (n = 25,651 in 2011, n = 29,442 in 2017); Swedish Pediatric Diabetes Quality Registry (SWEDIABKIDS)/National Diabetes Register (NDR), (n = 44,474 in 2011, n = 53,690 in 2017); and T1D Exchange (n = 16,198 in 2011, n = 17,087 in 2017) registries were analyzed by linear regression to compare mean HbA1c overall and by age group. Results: Controlling for age, sex, and T1D duration, HbA1c increased in the United States between 2011 and 2017, decreased in Sweden, and did not change in Germany/Austria. Controlling for sex and T1D duration, mean HbA1c decreased between 2011 and 2017 in all age cohorts in Sweden (P < 0.001). In the United States, HbA1c stayed the same for participants <6 years and 45 to <65 years and increased in all other age groups (P < 0.05). In Germany/Austria, HbA1c stayed the same for participants <6 to <13 years and 18 to <25 years; decreased for participants ages 13 to <18 years (P < 0.01); and increased for participants >= 25 years (P < 0.05). Conclusions: The comparison of international trends in HbA1c makes it possible to identify differences, explore underlying causes, and share quality improvement processes. National quality improvement initiatives are well accepted in Europe but have yet to be implemented systematically in the United States. However, disparities created by the lack of universal access to health care coverage, unequal access to diabetes technologies (e.g., continuous glucose monitoring) regardless of insurance status, and high out-of-pocket cost for the underinsured ultimately limit the potential of quality improvement initiatives.

  • 12.
    Al-Motlaq, Mohammad
    et al.
    Hashemite Univ, Jordan.
    Neill, Sarah
    Univ Plymouth, England.
    Foster, Mandie Jane
    Edith Cowan Univ, Australia; Perth Childrens Hosp, Australia.
    Coyne, Imelda
    Trinity Coll Dublin, Ireland; Trinity Coll Dublin, Ireland.
    Houghton, Davina
    Edith Cowan Univ, Australia.
    Angelhoff, Charlotte
    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.
    Rising-Holmstrom, Malin
    Mid Sweden Univ, Sweden.
    Majamanda, Maureen
    Univ Malawi, Malawi; Consortium Adv Training Africa CARTA, Kenya.
    Position statement of the international network for child and family centered care: Child and family centred care during the COVID19 pandemic2021In: Journal of Pediatric Nursing: Nursing Care of Children and Families, ISSN 0882-5963, E-ISSN 1532-8449, Vol. 61, p. 140-143Article in journal (Refereed)
    Abstract [en]

    It is the position of the International Network for Child and Family Centered Care (INCFCC) that COVID-19 restrictions pose tremendous challenges for the health care team in their efforts to provide child and family centered care (CFCC). COVID-19 restrictions impact on the familys right to be presernt with their ill child and to contribute to the caring process. A limited number of articles have discussed challenges about the successful delivery of CFCC during the COVID-19 pandemic. Based on current literature, the INCFCC stresses the need for continuous facilitation implementation of child and family centred care as, it is essential for childrens physical and psychological wellbeing. Furthermore we believe that the families presence and participation holds more benefits than risks to the health of children, their families, and the health care team. (C) 2021 Elsevier Inc. All rights reserved.

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  • 13.
    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, Cristina A.
    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 Act of Copulation per se, without Considering Seminal Deposition, Change the Expression of Genes in the Porcine Female Genital Tract?2020In: International Journal of Molecular Sciences, ISSN 1661-6596, E-ISSN 1422-0067, Vol. 21, no 15, article id 5477Article in journal (Refereed)
    Abstract [en]

    Semen-through its specific sperm and seminal plasma (SP) constituents-induces changes of gene expression in the internal genital tract of pigs, particularly in the functional sperm reservoir at the utero-tubal junction (UTJ). Although seminal effects are similarly elicited by artificial insemination (AI), major changes in gene expression are registered after natural mating, a fact suggesting the act of copulation induces per se changes in genes that AI does not affect. The present study explored which pathways were solely influenced by copulation, affecting the differential expression of genes (DEGs) of the pre/peri-ovulatory genital tract (cervix, distal uterus, proximal uterus and UTJ) of estrus sows, 24 h after various procedures were performed to compare natural mating with AI of semen (control 1), sperm-free SP harvested from the sperm-peak fraction (control 2), sperm-free SP harvested from the whole ejaculate (control 3) or saline-extender BTS (control 4), using a microarray chip (GeneChip(R)porcine gene 1.0 st array). Genes related to neuroendocrine responses (ADRA1,ADRA2,GABRB2,CACNB2), smooth muscle contractility (WNT7A), angiogenesis and vascular remodeling (poFUT1,NTN4) were, among others, overrepresented with distal and proximal uterine segments exhibiting the highest number of DEGs. The findings provide novel evidence that relevant transcriptomic changes in the porcine female reproductive tract occur in direct response to the specific act of copulation, being semen-independent.

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  • 14.
    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. Spanish Natl Inst Agr & Food Res & Technol INIA CS, 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. Spanish Natl Inst Agr & Food Res & Technol INIA CS, Spain.
    Gardela, Jaume
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences. Ctr Recerca Sanitat Anim CReSA, Spain.
    Nieto, Helena
    Spanish Natl Inst Agr & Food Res & Technol INIA CS, Spain.
    de Mercado, Eduardo
    Spanish Natl Inst Agr & Food Res & Technol INIA CS, 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.
    MicroRNA expression in specific segments of the pig periovulatory internal genital tract is differentially regulated by semen or by seminal plasma2024In: Research in Veterinary Science, ISSN 0034-5288, E-ISSN 1532-2661, Vol. 168, article id 105134Article in journal (Refereed)
    Abstract [en]

    microRNAs play pivotal roles during mammalian reproduction, including the cross-talk between gametes, embryos and the maternal genital tract. Mating induces changes in the expression of mRNA transcripts in the female, but whether miRNAs are involved remains to be elucidated. In the current study, we mapped 181 miRNAs in the porcine peri-ovulatory female reproductive tract: Cervix (Cvx), distal and proximal uterus (Dist-Ut, ProxUt), Utero-tubal-junction (UTJ), isthmus (Isth), ampulla (Amp), and infundibulum (Inf) when exposed to semen (natural mating (NM) or artificial insemination (AI-P1)) or to infusions of sperm-free seminal plasma (SP): the first 10 mL of the sperm rich fraction (SP-P1) or the entire ejaculate (SP-E). Among the most interesting findings, NM decreased mir-671, implicated in uterine development and pregnancy loss prior to embryo implantation, in Cvx, Dist-UT, Prox-UT, Isth, and Inf, while it increased in Amp. NM and SP-E induced the downregulation of miRlet7A-1 (Dist-UT, Prox-UT), a regulator of immunity during pregnancy. miR-34C-1, a regulator of endometrial receptivity gene expression, was increased in Dist-UT, UTJ and Amp (NM), in Prox-UT (AI-P1), and in Amp (SPP1). miR-296, a modulator of the inflammatory response and apoptosis, was upregulated in the UTJ (all treatments). NM elicited the highest miRNA activity in the sperm reservoir (UTJ), suggesting that key-regulators such as miR-34c or miR-296 may modulate the metabolic processes linked to the adequate preparation for gamete encounter in the oviduct. Our results suggest that SP should be maintained in AI to warrant miRNA regulation within the female genital tract for reproductive success.

  • 15.
    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. 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.
    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.
    mRNA expression of oxidative-reductive proteins in boars with documented different fertility can identify relevant prognostic biomarkers2021In: Research in Veterinary Science, ISSN 0034-5288, E-ISSN 1532-2661, Vol. 141, p. 195-202Article in journal (Refereed)
    Abstract [en]

    Oxidative stress unbalance is a major factor causing impairment of sperm function and, ultimately, sperm death. In this study, we identified transcriptomic and proteomic markers for oxidative-related protectors from the generation of reactive oxygen species (ROS) in spermatozoa from breeding boars with documented high- or lowfertility. Particular attention was paid to glutathione peroxidases, and to transcripts related to DNA stabilization and compaction, as protamine and transition proteins. mRNA cargo analysis was performed using porcinespecific micro-arrays (GeneChip (R) miRNA 4.0 and GeneChip (R) Porcine Gene 1.0 ST) and qPCR validation. Differences between fertility-classed boars were ample among biomarkers; some upregulated only at protein level (catalase (CAT), superoxide dismutase 1 (SOD1) and glutathione proteins), or only at the mRNA level (ATOX1, Antioxidant Protein 1). In addition, protamines 2 and 3, essential for sperm DNA condensation and also transition proteins 1 and 2 (TNP1 and TNP2), required during histone-to-protamine replacement, were overexpressed in spermatozoa from high-fertile boars. This up-regulation seems concerted to reduce DNA accessibility to ROS attack, protecting the DNA. The upregulated intracellular phospholipid hydroperoxide glutathione peroxidase (GPx4), in high-fertile boars at mRNA level, can be considered a most relevant biomarker for fertility disclosure during sperm evaluation.

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  • 16.
    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. Univ Autonoma Barcelona, Spain.
    Martinez-Pastor, Felipe
    Univ Leon, Spain.
    Molecular Determinants of Seminal Plasma on Sperm Biology and Fertility2021In: International Journal of Molecular Sciences, ISSN 1661-6596, E-ISSN 1422-0067, Vol. 22, no 7, article id 3555Article in journal (Other academic)
    Abstract [en]

    n/a

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  • 17.
    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 1661-6596, 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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  • 18.
    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, Faculty of Medicine and Health Sciences, Core Facility.
    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 1439-0531, Vol. 55, no 3, p. 293-300Article 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.

  • 19.
    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. CSIC, Spain.
    Roca, Jordi
    Univ Murcia, Spain.
    Martinez, Emilio A.
    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.
    Mating modifies the expression of crucial oxidative-reductive transcripts in the pig oviductal sperm reservoir: is the female ensuring sperm survival?2023In: Frontiers in Endocrinology, E-ISSN 1664-2392, Vol. 14, article id 1042176Article in journal (Refereed)
    Abstract [en]

    BackgroundMating induces large changes in the female genital tract, warranting female homeostasis and immune preparation for pregnancy, including the preservation of crucial oxidative status among its pathways. Being highly susceptible to oxidative stress, sperm survival and preserved function depend on the seminal plasma, a protection that is removed during sperm handling but also after mating when spermatozoa enter the oviduct. Therefore, it is pertinent to consider that the female sperm reservoir takes up this protection, providing a suitable environment for sperm viability. These aspects have not been explored despite the increasing strategies in modulating the female status through diet control and nutritional supplementation. AimsTo test the hypothesis that mating modifies the expression of crucial oxidative-reductive transcripts across the entire pig female genital tract (cervix to infundibulum) and, particularly in the sperm reservoir at the utero-tubal junction, before ovulation, a period dominated by estrogen stimulation of ovarian as well as of seminal origin. MethodsThe differential expression of estrogen (ER) and progesterone (PR) receptors and of 59 oxidative-reductive transcripts were studied using a species-specific microarray platform, in specific segments of the peri-ovulatory sow reproductive tract in response to mating. ResultsMating induced changes along the entire tract, with a conspicuous downregulation of both ER and PR and an upregulation of superoxide dismutase 1 (SOD1), glutaredoxin (GLRX3), and peroxiredoxin 1 and 3 (PRDX1, PRDX3), among other NADH Dehydrogenase Ubiquinone Flavoproteins, in the distal uterus segment. These changes perhaps helped prevent oxidative stress in the area adjacent to the sperm reservoir at the utero-tubal junction. Concomitantly, there were a downregulation of catalase (CAT) and NADH dehydrogenase (ubiquinone) oxidoreductases 1 beta subcomplex, subunit 1 (NDUFB1) in the utero-tubal junction alongside an overall downregulation of CAT, SOD1, and PRDX3 in the ampullar and infundibulum segments. ConclusionsNatural mating is an inducer of changes in the expression of female genes commanding antioxidant enzymes relevant for sperm survival during sperm transport, under predominant estrogen influence through the bloodstream and semen. The findings could contribute to the design of new therapeutics for the female to improve oxidative-reductive balance.

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  • 20.
    Aminoff, Victoria
    et al.
    Linköping University, Department of Behavioural Sciences and Learning, Psychology. Linköping University, Faculty of Arts and Sciences. Linköping University, Department of Biomedical and Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Bobeck, Johan
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences.
    Hjort, Sofia
    Linköping University, Department of Behavioural Sciences and Learning. Linköping University, Faculty of Arts and Sciences.
    Sorliden, Elise
    Linköping University, Department of Behavioural Sciences and Learning. Linköping University, Faculty of Arts and Sciences.
    Ludvigsson, Mikael
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Department of Health, Medicine and Caring Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Psykiatricentrum, Psykiatriska kliniken i Linköping. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Acute Internal Medicine and Geriatrics.
    Berg, Matilda
    Linköping University, Department of Behavioural Sciences and Learning, Psychology. Linköping University, Faculty of Arts and Sciences.
    Andersson, Gerhard
    Linköping University, Department of Behavioural Sciences and Learning, Psychology. Linköping University, Faculty of Arts and Sciences. Linköping University, Department of Biomedical and Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Otorhinolaryngology. Karolinska Inst, Sweden.
    Tailored internet-based psychological treatment for psychological problems during the COVID-19 pandemic: A randomized controlled trial2023In: Internet Interventions, ISSN 2214-7829, Vol. 34, article id 100662Article in journal (Refereed)
    Abstract [en]

    The COVID-19 pandemic influence mental health in both infected and non-infected populations. In this study we examined if individually tailored internet-based cognitive behavioral therapy (ICBT) could be an effective treatment for psychological symptoms related to the pandemic. Following recruitment we included 76 participants who were randomized to either a treatment group (n = 37) or a waitlist control group (n = 39). The treatment group received 8 modules (out of 16 possible) during 8 weeks with weekly therapist support. We collected data on symptoms of depression, experienced quality of life, anxiety, stress, anger, insomnia, PTSD, and alcohol use before, after the treatment and at one year follow-up. Using multiple regression analysis, group condition was found to be a statistically significant predictor for a decrease, favoring the treatment group, in symptoms of depression, insomnia, and anger with small to moderate effect sizes. The improvements remained at one year follow-up. Group condition did not significantly predict changing symptoms regarding experienced quality of life, anxiety, stress, PTSD and alcohol use. Findings indicate that ICBT is an effective intervention for some psychological symptoms associated with the COVID-19 pandemic. There is a need for further studies on mechanisms of change and on tailored ICBT for problems associated with crises like the pandemic.

  • 21.
    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. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Abu Awad, Yara
    Concordia Univ, Canada.
    Gauvin, Lise
    Ctr Hosp Univ Montreal, Canada; Univ Montreal, Canada.
    Spencer, Nicholas James
    Univ Warwick, England.
    McGrath, Jennifer J.
    Concordia Univ, Canada.
    Clifford, Susan A.
    Murdoch Childrens Res Inst, Australia; Univ Melbourne, Australia.
    Nikiema, Beatrice
    Univ Montreal, Canada; Cree Board Hlth & Social Serv James Bay, Canada.
    Yang-Huang, Junwen
    Erasmus MC, Netherlands; Erasmus MC, Netherlands.
    Goldhaber-Fiebert, Jeremy D.
    Stanford Univ, CA 94305 USA.
    Markham, Wolfgang
    Univ Warwick, England.
    Mensah, Fiona K.
    Murdoch Childrens Res Inst, Australia; Univ Melbourne, Australia.
    van Grieken, Amy
    Erasmus MC, Netherlands.
    Raat, Hein
    Erasmus MC, Netherlands.
    Jaddoe, V. W. V.
    Erasmus MC, Netherlands; Erasmus MC, Netherlands; Erasmus MC, Netherlands.
    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.
    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.
    Household income and maternal education in early childhood and risk of overweight and obesity in late childhood: Findings from seven birth cohort studies in six high-income countries2022In: International Journal of Obesity, ISSN 0307-0565, E-ISSN 1476-5497, Vol. 46, p. 1703-1711Article in journal (Refereed)
    Abstract [en]

    Background/objectives This study analysed the relationship between early childhood socioeconomic status (SES) measured by maternal education and household income and the subsequent development of childhood overweight and obesity. Subjects/methods Data from seven population-representative prospective child cohorts in six high-income countries: United Kingdom, Australia, the Netherlands, Canada (one national cohort and one from the province of Quebec), USA, Sweden. Children were included at birth or within the first 2 years of life. Pooled estimates relate to a total of N = 26,565 included children. Overweight and obesity were defined using International Obesity Task Force (IOTF) cut-offs and measured in late childhood (8-11 years). Risk ratios (RRs) and pooled risk estimates were adjusted for potential confounders (maternal age, ethnicity, child sex). Slope Indexes of Inequality (SII) were estimated to quantify absolute inequality for maternal education and household income. Results Prevalence ranged from 15.0% overweight and 2.4% obese in the Swedish cohort to 37.6% overweight and 15.8% obese in the US cohort. Overall, across cohorts, social gradients were observed for risk of obesity for both low maternal education (pooled RR: 2.99, 95% CI: 2.07, 4.31) and low household income (pooled RR: 2.69, 95% CI: 1.68, 4.30); between-cohort heterogeneity ranged from negligible to moderate (p: 0.300 to < 0.001). The association between RRs of obesity by income was lowest in Sweden than in other cohorts. Conclusions There was a social gradient by maternal education on the risk of childhood obesity in all included cohorts. The SES associations measured by income were more heterogeneous and differed between Sweden versus the other national cohorts; these findings may be attributable to policy differences, including preschool policies, maternity leave, a ban on advertising to children, and universal free school meals.

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  • 22.
    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. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    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.
    Jones, Michael P.
    Macquarie Univ, Australia.
    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.
    Low maternal education increases the risk of Type 1 Diabetes, but not other autoimmune diseases: a mediating role of childhood BMI and exposure to serious life events2023In: Scientific Reports, E-ISSN 2045-2322, Vol. 13, no 1Article in journal (Refereed)
    Abstract [en]

    The objective of this paper was to investigate if socioeconomic status (SES), measured by maternal education and household income, influenced the risk of developing autoimmune disease (Type 1 Diabetes, Celiac disease, Juvenile Idiopathic Arthritis, Crohns disease, Ulcerative colitis, and autoimmune thyroid disease), or age at diagnosis, and to analyse pathways between SES and autoimmune disease. We used data from the All Babies in Southeast Sweden (ABIS) study, a population-based prospective birth cohort, which included children born 1997-1999. Diagnoses of autoimmune disease was collected from the Swedish National Patient Register Dec 2020. In 16,365 individuals, low maternal education, but not household income, was associated with increased risk of Type 1 Diabetes; middle education RR 1.54, 95% CI 1.06, 2.23; P 0.02, low education RR 1.81, 95% CI 1.04, 3.18; P 0.04. Maternal education and household income was not associated with any other autoimmune disease and did not influence the age at diagnosis. Part of the increased risk of Type 1 Diabetes by lower maternal education was mediated by the indirect pathway of higher BMI and higher risk of Serious Life Events (SLE) at 5 years of age. The risk of developing Type 1 Diabetes associated to low maternal education might be reduced by decreasing BMI and SLE during childhood.

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  • 23.
    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, 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.

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  • 24.
    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.
    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 1399-5448, Vol. 21, no 4, p. 621-627Article 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.

  • 25. Order onlineBuy this publication >>
    Anderzén, Johan
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences.
    Differences in glycemic control in type 1 diabetes children and adolescents: in a national and international perspective and the effect on microvascular complications in young adults2023Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    This thesis focuses on glycemic control measured as HbA1c in type 1 diabetes (T1D) patients during childhood and especially during adolescence, both in a Swedish and an international context, and relates the glycemic control to the risk of complications in young adults.  

    In studies I and II, the Swedish Pediatric Diabetes Quality Register (SWEDIABKIDS) and the Swedish National Diabetes Register (NDR) were used. More than 4000 young adults with T1D and data on HbA1c in NDR both in 2011 and 2012 as well as data on HbA1c in SWEDIABKIDS were used. The T1D patients with poor glycemic control during their teenage period had a risk for retinopathy several times higher than those with good glycemic control. The risk for micro- and macroalbuminuria was also higher in those with poor glycemic control and was most pronounced in the T1D patients with high HbA1c in both registers. Females had worse glycemic control than males during the teenage period and an increased risk of retinopathy as young adults.  

    In studies III and IV, pediatric diabetes quality register data from, respectively, eight and seven Western high-income countries were collected in the year 2013. Data on about 60 000 T1D patients were analyzed according to mean HbA1c levels in the countries and related to actual age and T1D duration to determine if there were differences in glycemic control between the countries. There were large differences in mean HbA1c between the countries, both when related to age and T1D duration. Despite the differences in mean HbA1c, the increase in mean HbA1c with increasing age and T1D duration was very similar in all countries.  

    The overall picture of these studies is that good glycemic control is very important to avoid complications of T1D as young adults, and it seems particularly important to maintain a good glycemic control during adolescence. Furthermore large differences in glycemic control in T1D patients in Western high-income countries were found. Despite the differences in glycemic control, the pattern of rising HbA1c with increasing age and duration of T1D was very similar in all countries. Females have worse glycemic control than males during their teenage period, both in Sweden and internationally, and they also have more retinopathy as young adults.   

    This thesis shows that it is of the utmost importance to treat T1D patients intensively directly after diagnosis, to treat the young T1D patients intensely and to reduce the rise in HbA1c with increasing age and duration of T1D in order to avoid complications early in life. Diabetes quality registers give the opportunity to compare results and share experiences, both within and between countries, so treatment of T1D can be designed in the best possible way and thereby minimize T1D complications. 

    List of papers
    1. Teenagers with poor metabolic control already have a higher risk of microvascular complications as young adults
    Open this publication in new window or tab >>Teenagers with poor metabolic control already have a higher risk of microvascular complications as young adults
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    2016 (English)In: Journal of diabetes and its complications, ISSN 1056-8727, E-ISSN 1873-460X, Vol. 30, no 3, p. 533-536Article in journal (Refereed) Published
    Abstract [en]

    Aims: To evaluate how HbA1c in adolescents with type 1 diabetes affects microvascular complications in young adults. Methods: All individuals registered in the Swedish paediatric diabetes quality registry (SWEDIABKIDS) 13-18 years of age, and as adults registered in the Swedish National Diabetes Registry (NDR) in both the years 2011 and 2012 were included, in total 4250 individuals. Results: Of the individuals with mean HbA1c >78 mmol/mol in SWEDIABKIDS 83.4% had retinopathy, 15.8% had microalbuminuria and 4.9% had macroalbuminuria in NDR. The logistic regression analysis showed that the OR to develop macroalbuminuria as a young adult was significantly higher in the group with mean HbA1c >78 mmol/mol in SWEDIABKIDS (p < 0.05). Among the patients with mean HbA1c above 78 mmol/mol in both registries there was a significantly higher proportion that had retinopathy, microalbuminuria (p < 0.001) and/or macroalbuminuria (p < 0.01) compared to the group with HbA1c below 57 mmol/mol in both registries. Only 6.5% of the persons in this study were over 30 years of age. Conclusions: Paediatric diabetes teams working with teenagers must be aware of the impact of good metabolic control during adolescence, and should intensify the care during this vulnerable period of life to reduce the risk of microvascular complications in young adults.

    Place, publisher, year, edition, pages
    ELSEVIER SCIENCE INC, 2016
    Keywords
    Type 1 diabetes; Teenagers; National quality register; Metabolic control; Microvasular complications
    National Category
    Clinical Medicine
    Identifiers
    urn:nbn:se:liu:diva-127423 (URN)10.1016/j.jdiacomp.2015.12.004 (DOI)000372940300024 ()26775554 (PubMedID)
    Note

    Funding Agencies|Ostergotland County Council; Futurum the Academy for Health and Care; Jonkoping County Council; FORSS- Medical Research Council of Southeast Sweden

    Available from: 2016-05-01 Created: 2016-04-26 Last updated: 2023-02-22
    2. Teenage girls with type 1 diabetes have poorer metabolic control than boys and face more complications in early adulthood
    Open this publication in new window or tab >>Teenage girls with type 1 diabetes have poorer metabolic control than boys and face more complications in early adulthood
    Show others...
    2016 (English)In: Journal of diabetes and its complications, ISSN 1056-8727, E-ISSN 1873-460X, Vol. 30, no 5, p. 917-922Article in journal (Refereed) Published
    Abstract [en]

    Aims: To compare metabolic control between males and females with type 1 diabetes during adolescence and as young adults, and relate it to microvascular complications. Methods: Data concerning 4000 adolescents with type 1 diabetes registered in the Swedish paediatric diabetes quality registry, and above the age of 18 years in the Swedish National Diabetes Registry was used. Results: When dividing HbA1c values in three groups; amp;lt; 7.4% (57 mmol/mol), 7.4-93% (57-78 mmol/mol) and amp;gt;9.3% (78 mmol/mol), there was a higher proportion of females in the highest group during adolescence. In the group with the highest HbA1c values during adolescence and as adults, 51.7% were females, expected value 46.2%; in the group with low HbA1c values in both registries, 34.2% were females, p amp;lt; 0.001. As adults, more females had retinopathy, p amp;lt; 0.05. Females had higher mean HbAlc values at diagnosis, 112 vs. 10.9% (99 vs. 96 mmol/mol), p amp;lt; 0.03, during adolescence, 8.5 vs. 82% (69 vs. 66 mmol/mol) p amp;lt; 0.01, but not as young adults. Conclusions: Worse glycaemic control was found in adolescent females, and they had a higher frequency of microvascular complications. Improved paediatric diabetes care is of great importance for increasing the likelihood of lower mortality and morbidity later in life. (C) 2016 Elsevier Inc. All rights reserved.

    Place, publisher, year, edition, pages
    ELSEVIER SCIENCE INC, 2016
    Keywords
    HbA1c; Type 1 diabetes; Gender; Microvascular complications; Quality of care
    National Category
    Endocrinology and Diabetes
    Identifiers
    urn:nbn:se:liu:diva-130403 (URN)10.1016/j.jdiacomp.2016.02.007 (DOI)000378759700028 ()27052153 (PubMedID)
    Note

    Funding Agencies|Association of Local Authorities and Regions, SALAR; Futurum - Academy for Health and Care, Jonkoping County Council, Sweden

    Available from: 2016-08-15 Created: 2016-08-05 Last updated: 2023-02-22
    3. International benchmarking in type 1 diabetes: Large difference in childhood HbA1c between eight high-income countries but similar rise during adolescence-A quality registry study
    Open this publication in new window or tab >>International benchmarking in type 1 diabetes: Large difference in childhood HbA1c between eight high-income countries but similar rise during adolescence-A quality registry study
    Show others...
    2020 (English)In: Pediatric Diabetes, ISSN 1399-543X, E-ISSN 1399-5448, Vol. 21, no 4, p. 621-627Article in journal (Refereed) Published
    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.

    Place, publisher, year, edition, pages
    WILEY, 2020
    Keywords
    adolescents; children; HbA1c; quality registry; type 1 diabetes
    National Category
    Pediatrics
    Identifiers
    urn:nbn:se:liu:diva-165402 (URN)10.1111/pedi.13014 (DOI)000525890100001 ()32249476 (PubMedID)
    Note

    Funding Agencies|England Department of Health Policy Research Programme; EU-IMI2 consortium INNODIA; European Foundation for the Study of Diabetes; Futurum Academy for Health and Care; German Centre for Diabetes Research; German Diabetes Association; Health Research Fund of Central Denmark Region; Helmsley Charitable Trust; National Institute for Health Research Biomedical Research Centre at Great Ormond Street Hospital for Children NHS Foundation Trust and University College London; Welsh Government; South-Eastern Norway Regional Health Authority; Swedish Association of Local Authorities and Regions (SALAR); NHS England

    Available from: 2020-04-30 Created: 2020-04-30 Last updated: 2023-02-22Bibliographically approved
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  • 26.
    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. 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.
    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 1471-0528, Vol. 127, no 9, p. 1090-1099Article 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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  • 27.
    Angelhoff, Charlotte
    et al.
    Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus. Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences.
    Grundström, Hanna
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Norrköping. Linköping University, Department of Health, Medicine and Caring Sciences, Division of Nursing Sciences and Reproductive Health. Linköping University, Department of Biomedical and Clinical Sciences.
    Supporting girls with painful menstruation - A qualitative study with school nurses in Sweden2023In: Journal of Pediatric Nursing: Nursing Care of Children and Families, ISSN 0882-5963, E-ISSN 1532-8449, Vol. 68, p. e109-e115Article in journal (Refereed)
    Abstract [en]

    Background: Painful menstruation is common among girls. To optimize school nurses' work more knowledgeabout their experiences of supporting these girls is needed. The aim of this study was to describe school nurses'experiences of supporting girls with menstrual pain.Methods: Interviews were conducted with 15 school nurses in Sweden and analyzed using thematic analysis.Results: Three themes emerged: Taking menstrual pain seriously, Being a disseminator of knowledge, andExternal conditions for conducting professional work as a school nurse.Conclusion: School nurses felt competent in supporting girls with menstrual pain. However, they lacked struc-tural, written guidelines and routines for how to treat, support, follow-up and refer girls with menstrual pain.Practice implications: School education about menstruation and sexual health needs to be strengthened. Cooper-ation with other healthcare facilities and networks with other school nurses should be increased. Specific guide-lines on how to support girls with menstrual pain should be implemented.

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  • 28.
    Angelhoff, Charlotte
    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. Ersta Skondal Bracke Univ Coll, Sweden.
    Johansson, Peter
    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, Local Health Care Services in East Östergötland, Department of Internal Medicine in Norrköping.
    Svensson, Erland
    Swedish Def Res Agcy, Linkoping, Sweden.
    Sundell, Anna Lena
    Inst Postgrad Dent Educ, Sweden; Jonkoping Univ, Sweden.
    Correction: Swedish translation and validation of the Pediatric Insomnia Severity Index (vol 20, 253, 2020)2020In: BMC Pediatrics, ISSN 1471-2431, E-ISSN 1471-2431, BMC PEDIATRICS, Vol. 20, no 1, article id 333Article in journal (Other academic)
    Abstract [en]

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

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  • 29.
    Angelhoff, Charlotte
    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. Ersta Skondal Bracke Univ Coll, Sweden.
    Johansson, Peter
    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, Local Health Care Services in East Östergötland, Department of Internal Medicine in Norrköping.
    Svensson, Erland
    Swedish Def Res Agcy, Linkoping, Sweden.
    Sundell, Anna Lena Lena
    Inst Postgrad Dent Educ, Sweden; Jonkoping Univ, Sweden.
    Swedish translation and validation of the Pediatric Insomnia Severity Index2020In: BMC Pediatrics, ISSN 1471-2431, E-ISSN 1471-2431, BMC PEDIATRICS, Vol. 20, no 1, article id 253Article in journal (Refereed)
    Abstract [en]

    Background

    To increase health and well-being in young children, it is important to acknowledge and promote the child’s sleep behaviour. However, there is a lack of brief, validated sleep screening instruments for children. The aims of the study were to (1) present a Swedish translation of the PISI, (2) examine the factor structure of the Swedish version of PISI, and test the reliability and validity of the PISI factor structure in a sample of healthy children in Sweden.

    Methods

    The English version of the PISI was translated into Swedish, translated back into English, and agreed upon before use. Parents of healthy 3- to 10-year-old children filled out the Swedish version of the PISI and the generic health-related quality of life instrument KIDSCREEN-27 two times. Exploratory and confirmatory factor analyses for baseline and test-retest, structural equation modelling, and correlations between the PISI and KIDSCREEN-27 were performed.

    Results

    In total, 160 parents filled out baseline questionnaires (test), whereof 100 parents (63%) filled out the follow-up questionnaires (retest). Confirmative factor analysis of the PISI found two correlated factors: sleep onset problems (SOP) and sleep maintenance problems (SMP). The PISI had substantial construct and test-retest reliability. The PISI factors were related to all KIDSCREEN-27 dimensions.

    Conclusions

    The Swedish version of the PISI is applicable for screening sleep problems and is a useful aid in dialogues with families about sleep.

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  • 30.
    Angelhoff, Charlotte
    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.
    Sjolie, Hege
    Oslo Metropolitan Univ, Norway.
    Mörelius, Evalotte
    School of Nursing and Midwifery, Edith Cowan University, Joondalup, WA, Australia; Perth Children’s Hospital, Nedlands, WA, Australia.
    Loyland, Borghild
    Oslo Metropolitan Univ, Norway.
    Like Walking in a Fog: Parents' perceptions of sleep and consequences of sleep loss when staying overnight with their child in hospital2020In: Journal of Sleep Research, ISSN 0962-1105, E-ISSN 1365-2869, Vol. 29, no 2, article id e12945Article in journal (Refereed)
    Abstract [en]

    Disruption of parental sleep in hospital, with frequent awakenings and poor sleep quality, limits the parents resources to meet the childs needs and maintain parental wellbeing. The aim of the study was to explore and describe how parents perceive their sleep when staying overnight with their sick child in hospital. A further aim was to explore and describe parents perception of what circumstances influence their sleep in the hospital. Twenty-two parents who were accommodated with their sick child (0-17 years) in paediatric wards in Norway and Sweden participated. Interviews were conducted during the hospital stay to elicit their perspectives. Phenomenography was used to analyse data. Two descriptive categories were found: (a) "Perceptions of sleep", with two sub-categories: "Sleep in the paediatric ward" and "Consequences of sleep loss"; and (b) "Circumstances influencing sleep in the paediatric ward" with three sub-categories: "The importance of the family", "Information and routines at the paediatric ward", and "Accommodation facilities". Parents sleep and needs must be acknowledged in paediatric wards. An individual plan of care for the upcoming night could be a valuable tool for both the parents and nurses. The childs medical needs must be met with respect to the parents willingness to take part in the childs care during the night, and the need for rest and sleep for both parent and child.

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  • 31.
    Angelhoff, Charlotte
    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. Ersta Skondal Bracke Univ Coll, Sweden.
    Sveen, Josefin
    Ersta Skondal Bracke Univ Coll, Sweden; Uppsala Univ, Sweden.
    Alvariza, Anette
    Ersta Skondal Bracke Univ Coll, Sweden; Dalen Hosp, Sweden.
    Weber-Falk, Megan
    Ersta Skondal Bracke Univ Coll, Sweden.
    Kreicbergs, Ulrika
    Ersta Skondal Bracke Univ Coll, Sweden; Karolinska Inst, Sweden.
    Communication, self-esteem and prolonged grief in parent-adolescent dyads, 1 - 4 years following the death of a parent to cancer2021In: European Journal of Oncology Nursing, ISSN 1462-3889, E-ISSN 1532-2122, Vol. 50, article id 101883Article in journal (Refereed)
    Abstract [en]

    Purpose: Talking and grieving together may be advantageous for maintaining belief in a meaningful future and can help bereaved adolescents and their parents to cope better with the situation. The aim of this study was to explore communication, self-esteem and prolonged grief in adolescent-parent dyads, following the death of a parent to cancer. Method: This study has a descriptive and comparative design. Twenty family dyads consisting of parentally bereaved adolescents (12 & ndash;19 years) and their widowed parents completed the Parent and Adolescent Communication Scale, Rosenberg Self-Esteem Scale and Prolonged Grief-13, 1 & ndash;4 years following the death of a parent. Results: Twelve family dyads reported normal-high parent-adolescent communication, 11 dyads rated normal high self-esteem. Two adolescents and three parents scored above the cut-off for possible prolonged grief disorder (>= 35), none of these were in the same dyads. There was a difference (p < .05) between boys (mean 40.0) and girls (mean 41.9) with regard to open family communication, as assessed by parents. Girls reported lower self-esteem (mean 26.0) than boys (mean 34.1, p < .01). Conclusions: This study provides insights from parentally bereaved families which indicate that despite experiencing the often-traumatic life event of losing a parent or partner, most participants reported normal parent adolescent communication, normal self-esteem and few symptoms of prolonged grief. The potential usefulness of identifying families who may need professional support in family communication following the death of a parent is discussed.

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  • 32.
    Armuand, Gabriela
    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.
    Skoog Svanberg, Agneta
    Department of Womens and Childrens Health, Uppsala University, Sweden.
    Lampic, Claudia
    Department of Womens and Childrens Health, Karolinska Institutet, Sweden; Department of Public Health and Caring Sciences, Uppsala University, Sweden.
    Elenis, Evangelia
    Department of Womens and Childrens Health, Uppsala University, Sweden.
    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.
    Attitudes among paediatric healthcare professionals in Sweden towards sperm donation to single women: a survey study2020In: Fertility research and practice, ISSN 2054-7099, Vol. 6Article in journal (Refereed)
    Abstract [en]

    The number of families conceived through sperm donation to single women is increasing. However, there is limited knowledge about health care professionals attitudes towards solo-mothers by choice, and there is some indication that professionals personal opinions influence their care of individuals who use alternate ways to build a family. The primary aim of the study was to investigate attitudes towards, and experiences of, families following sperm donation to single women among healthcare professionals working in primary child healthcare.

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  • 33.
    Arnqvist, Hans
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Department of Endocrinology.
    Westerlund, Malin C.
    Linköping University, Department of Biomedical and Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Ophthalmology in Linköping.
    Fredrikson, Mats
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. 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.
    Nordwall, Maria
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Norrköping.
    Impact of HbA(1c) Followed 32 Years From Diagnosis of Type 1 Diabetes on Development of Severe Retinopathy and Nephropathy: The VISS Study2022In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 45, no 11, p. 2675-2682Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE To evaluate HbA(1c) followed from diagnosis, as a predictor of severe microvascular complications (i.e., proliferative diabetic retinopathy [PDR] and nephropathy [macroalbuminuria]). RESEARCH DESIGN AND METHODS In a population-based observational study, 447 patients diagnosed with type 1 diabetes before 35 years of age from 1983 to 1987 in southeast Sweden were followed from diagnosis until 2019. Long-term weighted mean HbA(1c) (wHbA(1c)) was calculated by integrating the area under all HbA(1c) values. Complications were analyzed in relation to wHbA(1c) categorized into five levels. RESULTS After 32 years, 9% had no retinopathy, 64% non-PDR, and 27% PDR, and 83% had no microalbuminuria, 9% microalbuminuria, and 8% macroalbuminuria. Patients with near-normal wHbA(1c) did not develop PDR or macroalbuminuria. The lowest wHbA(1c) values associated with development of PDR and nephropathy (macroalbuminuria) were 7.3% (56 mmol/mol) and 8.1% (65 mmol/mol), respectively. The prevalence of PDR and macroalbuminuria increased with increasing wHbA(1c), being 74% and 44% in the highest category, wHbA(1c) >9.5% (>80 mmol/mol). In comparison with the follow-up done after 20-24 years duration, the prevalence of PDR had increased from 14 to 27% and macroalbuminuria from 4 to 8%, and both appeared at lower wHbA(1c) values. CONCLUSIONS wHbA(1c) followed from diagnosis is a very strong biomarker for PDR and nephropathy, the prevalence of both still increasing 32 years after diagnosis. To avoid PDR and macroalbuminuria in patients with type 1 diabetes, an HbA(1c) <7.0% (53 mmol/mol) and as normal as possible should be recommended when achievable without severe hypoglycemia and with good quality of life.

  • 34.
    Aubert, Adrien
    et al.
    Univ Paris Cite, France.
    Costa, Raquel
    Univ Porto, Portugal; Lab Invest Integrat & Translac Saude Populac ITR, Portugal.
    Johnson, Samantha
    Univ Leicester, England.
    Ådén, Ulrika
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences. Karolinska Inst, Sweden.
    Cuttini, Marina
    Bambino Gesu Pediat Hosp, Italy.
    Koopman-Esseboom, Corine
    Univ Med Ctr, Netherlands.
    Lebeer, Jo
    Univ Antwerp, Belgium.
    Varendi, Heili
    Univ Tartu, Estonia.
    Zemlin, Michael
    Saarland Univ Hosp, Germany.
    Pierrat, Veronique
    Univ Paris Cite, France; Dept Neonatol, France.
    Zeitlin, Jennifer
    Univ Paris Cite, France.
    SHIPS Res grp,
    Risk factors for cerebral palsy and movement difficulties in 5-year-old children born extremely preterm2023In: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447Article in journal (Refereed)
    Abstract [en]

    BackgroundMotor impairment is common after extremely preterm (EPT, <28 weeks gestational age (GA)) birth, with cerebral palsy (CP) affecting about 10% of children and non-CP movement difficulties (MD) up to 50%. This study investigated the sociodemographic, perinatal and neonatal risk factors for CP and non-CP MD.MethodsData come from a European population-based cohort of children born EPT in 2011-2012 in 11 countries. We used multinomial logistic regression to assess risk factors for CP and non-CP MD (Movement Assessment Battery for Children - 2nd edition <= 5th percentile) compared to no MD (>15th percentile) among 5-year-old children.ResultsCompared to children without MD (n = 366), young maternal age, male sex and bronchopulmonary dysplasia were similarly associated with CP (n = 100) and non-CP MD (n = 224) with relative risk ratios (RRR) ranging from 2.3 to 3.6. CP was strongly related to severe brain lesions (RRR >10), other neonatal morbidities, congenital anomalies and low Apgar score (RRR: 2.4-3.3), while non-CP MD was associated with primiparity, maternal education, small for GA (RRR: 1.6-2.6) and severe brain lesions, but at a much lower order of magnitude.ConclusionCP and non-CP MD have different risk factor profiles, with fewer clinical but more sociodemographic risk factors for non-CP MD.ImpactYoung maternal age, male sex and bronchopulmonary dysplasia similarly increased risks of both cerebral palsy and non-cerebral palsy movement difficulties.Cerebral palsy was strongly related to clinical risk factors including severe brain lesions and other neonatal morbidities, while non-cerebral palsy movement difficulties were more associated with sociodemographic risk factors.These results on the similarities and differences in risk profiles of children with cerebral palsy and non-cerebral palsy movement difficulties raise questions for etiological research and provide a basis for improving the identification of children who may benefit from follow-up and early intervention.

  • 35.
    Aubert, Adrien M.
    et al.
    Univ Paris Cite, France.
    Costa, Raquel
    Univ Porto, Portugal; Lab Invest Integrat & Translac Saude Populac, Portugal.
    Johnson, Samantha
    Univ Leicester, England.
    Ådén, Ulrika
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences. Karolinska Inst, Sweden.
    Pierrat, Veronique
    Univ Paris Cite, France; Ctr Hosp Intercommunal Creteil, France.
    Cuttini, Marina
    Bambino Gesu Pediat Hosp, Italy.
    Mannamaa, Mairi
    Univ Tartu, Estonia.
    Sarrechia, Iemke
    Univ Antwerp, Belgium.
    Lebeer, Jo F.
    Erasmus MC, Netherlands.
    Van Heijst, Arno F. F.
    Erasmus MC, Netherlands.
    Maier, Rolf F.
    Philipps Univ Marburg, Germany.
    Sentenac, Mariane
    Univ Paris Cite, France.
    Zeitlin, Jennifer
    Univ Paris Cite, France; Maternite Port Royal 53, France.
    Developmental motor problems and health-related quality of life in 5-year-old children born extremely preterm: A European cohort study2023In: Developmental Medicine & Child Neurology, ISSN 0012-1622, E-ISSN 1469-8749, Vol. 65, no 12, p. 1617-1628Article in journal (Refereed)
    Abstract [en]

    Aim To measure the association between cerebral palsy (CP) and non-CP-related movement difficulties and health-related quality of life (HRQoL) among 5-year-old children born extremely preterm (<28 weeks gestational age). Method We included 5-year-old children from a multi-country, population-based cohort of children born extremely preterm in 2011 to 2012 in 11 European countries (n = 1021). Children without CP were classified using the Movement Assessment Battery for Children, Second Edition as having significant movement difficulties (<= 5th centile of standardized norms) or being at risk of movement difficulties (6th-15th centile). Parents reported on a clinical CP diagnosis and HRQoL using the Pediatric Quality of Life Inventory. Associations were assessed using linear and quantile regressions. Results Compared to children without movement difficulties, children at risk of movement difficulties, with significant movement difficulties, and CP had lower adjusted HRQoL total scores (beta [95% confidence interval] = -5.0 [-7.7 to -2.3], -9.1 [-12.0 to -6.1], and - 26.1 [-31.0 to -21.2]). Quantile regression analyses showed similar decreases in HRQoL for all children with CP, whereas for children with non-CP-related movement difficulties, reductions in HRQoL were more pronounced at lower centiles. Interpretation CP and non-CP-related movement difficulties were associated with lower HRQoL, even for children with less severe difficulties. Heterogeneous associations for non-CP-related movement difficulties raise questions for research about mitigating and protective factors.

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  • 36.
    Axelsson, Daniel
    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.
    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.
    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.
    Maternal obesity and the risk of postpartum infections according to mode of delivery2023In: The Journal of Maternal-Fetal & Neonatal Medicine, ISSN 1476-7058, E-ISSN 1476-4954, Vol. 36, no 2, article id 2245102Article in journal (Refereed)
    Abstract [en]

    Objective The aim of the present study was to assess the impact of different maternal Body Mass Index (BMI) classes on the risk of postpartum endometritis, wound infection, and breast abscess after different modes of delivery. Secondly to estimate how the risk of postpartum infection varies with different maternal BMI groups after induction of labor and after obstetric anal sphincter injuries. Methods A population-based observational study including women who gave birth during eight years (N = 841,780). Data were collected from three Swedish Medical Health Registers, the Swedish Medical Birth Register, the Swedish National Patient Register, and the Swedish Prescribed Drug Register. Outcomes were defined by ICD-10 codes given within eight weeks postpartum. The reference population was uninfected women. Odds ratios were determined using Mantel-Haenszel technique. Year of delivery, maternal age, parity and smoking in early pregnancy were considered as confounders. Results There was a dose-dependent relationship between an increasing maternal BMI and a higher risk for postpartum infections. Women in obesity class II and III had an increased risk for endometritis after normal vaginal delivery aOR 1.45 (95% CI: 1.29-1.63) and for wound infections after cesarean section aOR 3.83 (95% CI: 3.39-4.32). There was no difference in how maternal BMI affected the association between cesarean section and wound infection, regardless of whether it was planned or emergent. Women in obesity class II and III had a lower risk of breast abscess compared with normal-weight women, aOR 0.47 (95% CI: 0.38-0.58). The risk of endometritis after labor induction decreased with increasing maternal BMI. The risk of wound infection among women with an obstetrical sphincter injury decreased with increasing BMI. Conclusion This study provides new knowledge about the impact of maternal BMI on the risk of postpartum infections after different modes of delivery. There was no difference in how BMI affected the association between cesarean section and wound infections, regardless of whether it was a planned cesarean section or an emergency cesarean section.

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  • 37.
    Babarro, Izaro
    et al.
    Univ Basque Country UPV EHU, Spain; Biodonostia Hlth Res Inst, Spain; Tolosa Hiribidea 70, Spain.
    Andiarena, Ainara
    Univ Basque Country UPV EHU, Spain; Biodonostia Hlth Res Inst, Spain.
    Fano, Eduardo
    Univ Basque Country UPV EHU, Spain; Biodonostia Hlth Res Inst, Spain.
    Garcia-Baquero, Gonzalo
    Biodonostia Hlth Res Inst, Spain; Inst Salud Carlos 3, Spain.
    Lebena, Andrea
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences.
    Arranz-Freijo, Enrique B.
    Univ Basque Country UPV EHU, Spain; Biodonostia Hlth Res Inst, Spain.
    Ibarluzea, Jesus
    Univ Basque Country UPV EHU, Spain; Biodonostia Hlth Res Inst, Spain; Inst Salud Carlos 3, Spain; Minist Hlth Basque Govt, Spain.
    Do prepubertal hormones, 2D:4D index and psychosocial context jointly explain 11-year-old preadolescents involvement in bullying?2022In: Biological Psychology, ISSN 0301-0511, E-ISSN 1873-6246, Vol. 172, article id 108379Article in journal (Refereed)
    Abstract [en]

    Background: Bullying is a type of aggressive behavior that occurs repeatedly and intentionally in school environments and where there is a power imbalance. The main objective of this study was to analyze the association that hormones and the psychosocial context jointly have with bullying behavior. Method: Participants were 302 11-year-old preadolescents from the Gipuzkoan cohort of the INMA Project. Bullying was assessed using the Olweus Bully/victim Questionnaire. Prenatal sexual hormones were assessed by calculating 2D:4D ratio and in order to measure prepubertal testosterone and cortisol levels saliva samples were collected within a week of each other. Additionally, various psychosocial factors were evaluated: executive function, family context, school environment and social context. To analyze our complex hypothesis, six metamodels were tested using structural equation modeling. Results: In relation to victims, results showed that victimization was related to worse school environment perception in boys, and higher stress and conflict in the family in girls. In the case of their involvement in bullying as a bully, lower salivary cortisol levels, worse school environment perception and lower peers and social support was related to being more frequently involved as a bully in boys, while having more family stress and conflict was related with being a bully in girls. Conclusions: This approach makes it possible not only to explore the different biological and psychosocial factors affect bullying behavior, but also to explore associations between the predictor variables.

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  • 38.
    Bach Jensen, Georg
    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.
    Ahlsson, Fredrik
    Uppsala Univ, Sweden.
    Domellöf, Magnus
    Umeå Univ, Sweden.
    Elfvin, Anders
    Sahlgrens Acad, Sweden; Sahlgrens Univ Hosp, Sweden.
    Naver, Lars
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    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.
    Nordic study on human milk fortification in extremely preterm infants: a randomised controlled trial the N-forte trial2021In: BMJ Open, E-ISSN 2044-6055, Vol. 11, no 11, article id e053400Article in journal (Refereed)
    Abstract [en]

    Introduction The mortality rate of extremely low gestational age (ELGA) (born <gestational week 28+0) infants remains high, and severe infections and necrotising enterocolitis (NEC) are common causes of death. Preterm infants receiving human milk have lower incidence of sepsis and NEC than those fed a bovine milk-based preterm formula. Despite this, fully human milk fed ELGA infants most often have a significant intake of cows milk protein from bovine-based protein fortifier. The aim of this study is to evaluate whether the supplementation of human milk-based, as compared with bovine-based, nutrient fortifier reduces the prevalence of NEC, sepsis and mortality in ELGA infants exclusively fed with human milk. Methods and analysis A randomised-controlled multicentre trial comparing the effect of a human breast milk-based fortifier with a standard bovine protein-based fortifier in 222-322 ELGA infants fed human breast milk (mothers own milk and/or donor milk). The infants will be randomised to either fortifier before reaching 100 mU kg/day in oral feeds. The intervention, stratified by centre, will continue until the target postmenstrual week 34+0. The primary outcome is a composite of NEC, sepsis or death. Infants are characterised with comprehensive clinical and nutritional data collected prospectively from birth until hospital discharge. Stool, urine, blood and breast milk samples are collected for analyses in order to study underlying mechanisms. A follow-up focusing on neurological development and growth will be performed at 2 and 5.5 years of age. Health economic analyses will be made. Ethics and dissemination The study is conducted according to ICH/GCP guidelines and is approved by the regional ethical review board in Linkoping Sweden (Dnr 2018/193-31, Dnr 2018/384-32). Results will be presented at scientific meetings and published in peer-reviewed publications.

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  • 39.
    Badam, Tejaswi
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Bioinformatics. Linköping University, Faculty of Science & Engineering. Skovde Univ, Sweden.
    Hellberg, Sandra
    Linköping University, Department of Physics, Chemistry and Biology, Bioinformatics. Linköping University, Faculty of Science & Engineering.
    Bhai Mehta, Ratnesh
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences.
    Lechner-Scott, Jeannette
    Univ Newcastle, Australia; Hunter Med Res Inst, Australia; John Hunter Hosp, Australia.
    Lea, Rodney A.
    Univ Newcastle, Australia; Hunter Med Res Inst, Australia; Queensland Univ Technol, Australia.
    Tost, Jorg
    CEA Inst Biol Francois Jacob, France.
    Mariette, Xavier
    Univ Paris Saclay, France.
    Svensson-Arvelund, Judit
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences.
    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.
    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.
    Berg, Göran
    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.
    Jenmalm, Maria
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. 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.
    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.
    CD4(+) T-cell DNA methylation changes during pregnancy significantly correlate with disease-associated methylation changes in autoimmune diseases2022In: Epigenetics, ISSN 1559-2294, E-ISSN 1559-2308, Vol. 17, no 9, p. 1040-1055Article in journal (Refereed)
    Abstract [en]

    Epigenetics may play a central, yet unexplored, role in the profound changes that the maternal immune system undergoes during pregnancy and could be involved in the pregnancy-induced modulation of several autoimmune diseases. We investigated changes in the methylome in isolated circulating CD4(+) T-cells in non-pregnant and pregnant women, during the 1(st) and 2(nd) trimester, using the Illumina Infinium Human Methylation 450K array, and explored how these changes were related to autoimmune diseases that are known to be affected during pregnancy. Pregnancy was associated with several hundreds of methylation differences, particularly during the 2(nd) trimester. A network-based modular approach identified several genes, e.g., CD28, FYN, VAV1 and pathways related to T-cell signalling and activation, highlighting T-cell regulation as a central component of the observed methylation alterations. The identified pregnancy module was significantly enriched for disease-associated methylation changes related to multiple sclerosis, rheumatoid arthritis and systemic lupus erythematosus. A negative correlation between pregnancy-associated methylation changes and disease-associated changes was found for multiple sclerosis and rheumatoid arthritis, diseases that are known to improve during pregnancy whereas a positive correlation was found for systemic lupus erythematosus, a disease that instead worsens during pregnancy. Thus, the directionality of the observed changes is in line with the previously observed effect of pregnancy on disease activity. Our systems medicine approach supports the importance of the methylome in immune regulation of T-cells during pregnancy. Our findings highlight the relevance of using pregnancy as a model for understanding and identifying disease-related mechanisms involved in the modulation of autoimmune diseases.

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  • 40.
    Bang, Peter
    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.
    Polak, Michel
    Hop Univ Necker Enfants Malad, France; France Univ Paris Cite, France.
    Bossowski, Artur
    Med Univ Bialystok, Poland.
    Maghnie, Mohamad
    IRCCS Ist Giannina Gaslini, Italy; Univ Genoa, Italy.
    Argente, Jesus
    Univ Nino Jesus, Spain; Univ Autonoma Madrid, Spain; Inst Salud Carlos III, Spain; IMDEA Food Inst, Spain.
    Ramon-Krauel, Marta
    Hosp St Joan De Deu, Spain; Inst Salud Carlos III, Spain.
    Sert, Caroline
    Ipsen Pharma, France.
    Perrot, Valerie
    Ipsen Pharma, France.
    Mazain, Sarah
    Ipsen Pharma, France.
    Woelfle, Joachim
    Friedrich Alexander Univ FAU Erlangen Nurnberg, Germany; Friedrich Alexander Univ FAU Erlangen Nurnberg, Germany.
    Frequency and Predictive Factors of Hypoglycemia in Patients Treated With rhIGF-1: Data From the Eu-IGFD Registry2024In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 109, no 1, p. 46-56Article in journal (Refereed)
    Abstract [en]

    Context The European Increlex & REG; Growth Forum Database (Eu-IGFD) is an ongoing surveillance registry (NCT00903110) established to collect long-term safety and effectiveness data on the use of recombinant human insulin-like growth factor-1 (rhIGF-1, mecasermin, Increlex) for the treatment of children/adolescents with severe primary insulin-like growth factor-1 deficiency (SPIGFD).Objective This analysis of Eu-IGFD data aimed to identify the frequency and predictive factors for hypoglycemia adverse events (AEs) in children treated with rhIGF-1.Methods Data were collected from December 2008 to May 2021. Logistic regression was performed to identify predictive risk factors for treatment-induced hypoglycemia AEs. Odds ratios (ORs) are presented with 95% CIs for each factor.Results In total, 306 patients were enrolled in the registry; 84.6% were diagnosed with SPIGFD. Patients who experienced & GE; 1 hypoglycemia AE (n = 80) compared with those with no hypoglycemia AEs (n = 224) had a lower mean age at treatment start (8.7 years vs 9.8 years), a more frequent diagnosis of Laron syndrome (27.5% vs 10.3%), and a history of hypoglycemia (18.8% vs 4.5%). Prior history of hypoglycemia (OR 0.25; 95% CI: [0.11; 0.61]; P = .002) and Laron syndrome diagnosis (OR 0.36; 95% CI: [0.18; 0.72]; P = .004) predicted future hypoglycemia AEs. Total hypoglycemia AEs per patient per treatment year was 0.11 and total serious hypoglycemia AEs per patient per treatment year was 0.01.Conclusion Hypoglycemia occurs more frequently in patients with prior history of hypoglycemia and/or Laron syndrome compared with patients without these risk factors, and these patients should be carefully monitored for this AE throughout treatment.

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  • 41.
    Bang, Peter
    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.
    Polak, Michel
    Univ Paris, France.
    Perrot, Valerie
    Ipsen Pharma, France.
    Sert, Caroline
    Ipsen Pharma, France.
    Shaikh, Haris
    Ipsen Pharm, Wales.
    Woelfle, Joachim
    Friedrich Alexander Univ Erlangen Nurnberg, Germany.
    Pubertal Timing and Growth Dynamics in Children With Severe Primary IGF-1 Deficiency: Results From the European Increlex(R) Growth Forum Database Registry2022In: Frontiers in Endocrinology, E-ISSN 1664-2392, Vol. 13, article id 812568Article in journal (Refereed)
    Abstract [en]

    BackgroundPuberty is delayed in untreated children and adolescents with severe primary IGF-1 deficiency (SPIGFD); to date, it has not been reported whether recombinant human insulin-like growth factor-1 mecasermin (rhIGF-1) treatment affects this. Pubertal growth outcomes were extracted from the European Increlex(R) Growth Forum Database (Eu-IGFD) Registry (NCT00903110). MethodsThe Eu-IGFD Registry includes children and adolescents aged 2 to 18 years with growth failure associated with SPIGFD who are treated with rhIGF-1. Reported outcomes include: age at last registration of Tanner stage 1 and first registration of Tanner stage 2-5 (T2-T5; based on breast development for girls and genital development for boys, respectively); maximum height velocity during each Tanner stage; and pubertal peak height velocity (PPHV). Data cut-off was 13 May 2019. ResultsThis analysis included 213 patients (132 boys and 81 girls). Mean (SD) age at last registration of T1 and first registration of T5 was 13.0 (2.0) and 16.3 (1.6) years, respectively, in boys and 11.6 (1.8) and 14.7 (1.5) years, respectively, in girls. Among patients reaching the end of puberty (25 boys and 11 girls), mean (SD) height SDS increased from -3.7 (1.4) at baseline in the Eu-IGFD Registry to -2.6 (1.4) at T5 in boys and from -3.1 (1.1) to -2.3 (1.5) in girls. Maximum height velocity was observed during T2 in girls and T3 in boys. Median (range) PPHV was 8.0 (0.3-13.0) cm/year in boys and 6.8 (1.3-9.6) cm/year in girls and occurred most frequently during T2. Overall, the adverse events seen in this analysis were in line with the known safety profile of rhIGF-1. ConclusionChildren and adolescents treated with rhIGF-1 for SPIGFD with growth failure experienced an increase in height SDS in prepubertal years compared with baseline. Despite 1.5 years delay in pubertal start and a delayed and slightly lower PPHV, height SDS gain during puberty was maintained.

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  • 42.
    Bang, Peter
    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.
    Woelfle, Joachim
    Univ Erlangen Nurnberg, Germany.
    Perrot, Valerie
    Ipsen Pharma, France.
    Sert, Caroline
    Ipsen Pharma, France.
    Polak, Michel
    Univ Paris, France.
    Effectiveness and safety of rhIGF1 therapy n patients with or without Laron syndrome2021In: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 184, no 2, p. 267-276Article in journal (Refereed)
    Abstract [en]

    Objective: The European Increlex (R) Growth Forum Database Registry monitors the effectiveness and safety of recombinant human insulin-like growth factor-1 (rhIGF1; mecasermin, Increlex (R)) therapy in patients with severe primary IGF1 deficiency (SPIGFD). We present data from patients with and without a reported genetic diagnosis of Laron syndrome (LS). Design: Ongoing, open-label, observational registry (NCT00903110). Methods: Children and adolescents receiving rhIGF1 therapy from 10 European countries were enrolled in 2008-2017 (n = 242). The treatment-naive/prepubertal (NPP) cohort (n = 138) was divided into subgroups based on reported genetic diagnosis of LS (n = 21) or non-LS (n = 117). Multivariate analysis of the NPP-non-LS subgroup was conducted to identify factors predictive of growth response (first-year-height standard deviation score (SDS) gain >= 0.3). Assessments included change in height and weight over 5 years and adverse events (AEs). Results: Height SDS gain from baseline was greater in the NPP-LS than the NPP-non-LS subgroup after 1 years treatment (P < 0.05). In the NPP-non-LS subgroup, 56% were responders; young age at baseline was a positive independent predictive factor (P < 0.001). NPP-non-LS-responders and the NPP-LS subgroup had a similar mean age (6.07 years vs 7.00 years) at baseline and height SDS gain in year 1 (0.64 vs 0.70), although NPP-non-LS-responders were taller (P < 0.001) at baseline. BMI SDS changes did not differ across subgroups. Treatment-emergent AEs were experienced by 65.3% of patients; hypoglycaemia was most common. Conclusions: In most NPP children with SPIGFD, with or without LS, rhIGF1 therapy promotes linear growth. The safety profile was consistent with previous studies.

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  • 43.
    Barcenilla, Hugo
    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.
    Pihl, Mikael
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Molecular Medicine and Virology. Linköping University, Faculty of Medicine and Health Sciences.
    Wahlberg, Jeanette
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Department of Endocrinology. Orebro Univ, Sweden; Orebro Univ, Sweden.
    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.
    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.
    Intralymphatic GAD-alum Injection Modulates B Cell Response and Induces Follicular Helper T Cells and PD-1+CD8+T Cells in Patients With Recent-Onset Type 1 Diabetes2022In: Frontiers in Immunology, E-ISSN 1664-3224, Vol. 12, article id 797172Article in journal (Refereed)
    Abstract [en]

    Antigen-specific immunotherapy is an appealing strategy to preserve beta-cell function in type 1 diabetes, although the approach has yet to meet its therapeutic endpoint. Direct administration of autoantigen into lymph nodes has emerged as an alternative administration route that can improve the efficacy of the treatment. In the first open-label clinical trial in humans, injection of aluminum-formulated glutamic acid decarboxylase (GAD-alum) into an inguinal lymph node led to the promising preservation of C-peptide in patients with recent-onset type 1 diabetes. The treatment induced a distinct immunomodulatory effect, but the response at the cell level has not been fully characterized. Here we used mass cytometry to profile the immune landscape in peripheral blood mononuclear cells from 12 participants of the study before and after 15 months of treatment. The immunomodulatory effect of the therapy included reduction of naive and unswitched memory B cells, increase in follicular helper T cells and expansion of PD-1+ CD69+ cells in both CD8+ and double negative T cells. In vitro stimulation with GAD(65) only affected effector CD8+ T cells in samples collected before the treatment. However, the recall response to antigen after 15 months included induction of CXCR3+ and CD11c+Tbet+ B cells, PD-1+ follicular helper T cells and exhausted-like CD8+ T cells. This study provides a deeper insight into the immunological changes associated with GAD-alum administration directly into the lymph nodes.

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  • 44.
    Barranco, Isabel
    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. University of Murcia, Murcia, Spain; University of Girona, Girona, Spain.
    Padilla, Lorena
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences. University of Murcia, Murcia, 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.
    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.
    Parrilla, Inmaculada
    University of Murcia, Murcia, Spain.
    Lucas, Xiomara
    University of Murcia, Murcia, Spain.
    Ferreira-Dias, Graça
    University of Lisbon, Lisbon, Portugal.
    Yeste, Marc
    University of Girona, Girona, 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.
    Roca, Jordi
    University of Murcia, Murcia, Spain.
    Seminal Plasma Modulates miRNA Expression by Sow Genital Tract Lining Explants2020In: Biomolecules, E-ISSN 2218-273X, Vol. 10, no 6, article id E933Article in journal (Refereed)
    Abstract [en]

    The seminal plasma (SP) modulates the female reproductive immune environment after mating, and microRNAs (miRNAs) could participate in the process. Considering that the boar ejaculate is built by fractions differing in SP-composition, this study evaluated whether exposure of mucosal explants of the sow internal genital tract (uterus, utero-tubal junction and isthmus) to different SP-fractions changed the profile of explant-secreted miRNAs. Mucosal explants retrieved from oestrus sows (n = 3) were in vitro exposed to: Medium 199 (M199, Control) or M199 supplemented (1:40 v/v) with SP from the sperm-rich fraction (SRF), the post-SRF or the entire recomposed ejaculate, for 16 h. After, the explants were cultured in M199 for 24 h to finally collect the media for miRNA analyses using GeneChip miRNA 4.0 Array (Affymetrix). Fifteen differentially expressed (False Discovery Rate (FDR) < 0.05 and Fold-change ≥ 2) miRNAs (11 down- versus 4 up-regulated) were identified (the most in the media of uterine explants incubated with SP from post-SRF). Bioinformatics analysis identified that predicted target genes of dysregulated miRNAs, mainly miR-34b, miR-205, miR-4776-3p and miR-574-5p, were involved in functions and pathways related to immune response. In conclusion, SP is able to elicit changes in the miRNAs profile secreted by female genital tract, ultimately depending SP-composition.

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  • 45.
    Barranco, Isabel
    et al.
    Univ Bologna, Italy.
    Rubio, Camila P.
    Univ Autonoma Barcelona, Spain; Univ Murcia, Spain.
    Tvarijonaviciute, Asta
    Univ Murcia, Spain; 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.
    Roca, Jordi
    Univ Murcia, Spain.
    Measurement of Oxidative Stress Index in Seminal Plasma Can Predict In Vivo Fertility of Liquid-Stored Porcine Artificial Insemination Semen Doses2021In: Antioxidants, ISSN 2076-3921, Vol. 10, no 8, article id 1203Article in journal (Refereed)
    Abstract [en]

    The study evaluated the relation between the oxidative stress index (OSI) in porcine seminal plasma (n = 76) with sperm resilience and in vivo fertility (farrowing rate and litter size of 3137 inseminated sows) of liquid-stored artificial insemination (AI) semen doses. The OSI was assessed as the ratio of advanced oxidation protein products to Trolox-equivalent antioxidant capacity, both measured using an automated analyzer. Sperm motility (computer-assisted sperm analyzer) and viability (flow cytometry) were evaluated in semen AI-doses at 0 and 72 h of storage at 17 degrees C. Sperm resilience was defined as the difference between storage intervals. Semen AI-doses were hierarchically clustered as having high, medium and low seminal OSI (p &lt; 0.001) with those of low displaying higher resilience (p &lt; 0.01). Boars were hierarchically clustered into two groups (p &lt; 0.001) as having either positive or negative farrowing rate and litter size deviation; the negative one showing higher seminal OSI (p &lt; 0.05). In sum, seminal OSI was negatively related to sperm motility and the in vivo fertility of liquid-stored boar semen AI-doses, with the receiver operating characteristic curve presenting seminal OSI as a good predictive biomarker of in vivo fertility of AI-boars (area under the curve: 0.815, p &lt; 0.05).

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  • 46.
    Barranco, Isabel
    et al.
    Univ Bologna, Italy.
    Sanchez-Lopez, Christian M.
    Univ Valencia, Spain; Univ Valencia, Spain.
    Bucci, Diego
    Univ Bologna, Italy.
    Alvarez-Barrientos, Alberto
    Univ Extremadura, 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.
    Marcilla, Antonio
    Univ Valencia, Spain; Univ Valencia, Spain.
    Roca, Jordi
    Univ Murcia, Spain.
    The Proteome of Large or Small Extracellular Vesicles in Pig Seminal Plasma Differs, Defining Sources and Biological Functions2023In: Molecular & Cellular Proteomics, ISSN 1535-9476, E-ISSN 1535-9484, Vol. 22, no 4, article id 100514Article in journal (Refereed)
    Abstract [en]

    Seminal plasma contains many morphologically hetero-geneous extracellular vesicles (sEVs). These are sequentially released by cells of the testis, epididymis, and accessory sex glands and involved in male and fe-male reproductive processes. This study aimed to define in depth sEV subsets isolated by ultrafiltration and size exclusion chromatography, decode their proteomic profiles using liquid chromatography-tandem mass spectrometry, and quantify identified proteins using sequential window acquisition of all theoretical mass spectra. The sEV subsets were defined as large (L-EVs) or small (S-EVs) by their protein concentration, morphology, size distribution, and EV-specific protein markers and purity. Liquid chromatography-tandem mass spectrometry identified a total of 1034 proteins, 737 of them quantified by SWATH in S-EVs, L-EVs, and non-EVs-enriched samples (18-20 size exclusion chromatography-eluted fractions). The differential expression analysis revealed 197 differentially abundant proteins between both EV subsets, S-EVs and L-EVs, and 37 and 199 between S-EVs and L-EVs versus non-EVs-enriched samples, respectively. The gene ontology enrichment analysis of differentially abundant proteins suggested, based on the type of protein detected, that S-EVs could be mainly released through an apocrine blebbing pathway and be involved in modulating the im-mune environment of the female reproductive tract as well as during sperm-oocyte interaction. In contrast, L-EVs could be released by fusion of multivesicular bodies with the plasma membrane becoming involved in sperm physiological processes, such as capacitation and avoidance of oxidative stress. In conclusion, this study provides a procedure capable of isolating subsets of EVs from pig seminal plasma with a high degree of purity and shows differences in the proteomic profile between EV subsets, indicating different sources and biological functions for the sEVs.

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  • 47.
    Barranco, Isabel
    et al.
    Univ Murcia, Spain; Univ Girona, Spain.
    Tvarijonaviciute, Asta
    Univ Murcia, Spain.
    Padilla, Lorena
    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.
    Roca, Jordi
    Univ Murcia, Spain.
    Lucas, Xiomara
    Univ Murcia, Spain.
    Delays in processing and storage of pig seminal plasma alters levels of contained antioxidants2021In: Research in Veterinary Science, ISSN 0034-5288, E-ISSN 1532-2661, Vol. 135, p. 416-423Article in journal (Refereed)
    Abstract [en]

    Seminal plasma (SP) antioxidants are considered biomarkers of sperm function and fertility for AI-boars. The current protocol for their measurement implies the SP was harvested immediately after ejaculation and prompt stored at -80 degrees C until analysis. Such protocol may be impractical for AI-centers. This study evaluated how SP levels of antioxidants were influenced by delays in (1) SP-harvesting (0 [control], 2 or 24 h at 17 degrees C after ejaculate collection), in (2) SP-freezing (0 [control] or 24 hat 17 degrees C after SP-harvesting) or (3) the temperature of storage (-80 degrees C [control] or - 20 degrees C). The SP-antioxidants evaluated were: glutathione peroxidase [GPx], superoxide dismutase [SOD], paraoxonase-1 [PON-1], trolox equivalent antioxidant capacity [TEAC] and oxidative stress index [OSI]. A total of 120 aliquots from 10 entire ejaculates were handled in three trials. They were centrifuged (1500 g, 10 min) for harvesting SP and antioxidants were measured with an Automatic Chemistry Analyzer. A 24 h-delay in harvesting the SP led to an increase (p 0.001) in TEAC and SOD SP-levels, and a decrease (p 0.05) of OSI and PON-1. Similarly, a 24 h-delay to freeze the SP increased (p 0.01) TEAC values and decreased (p 0.01) PON-1 and GPx activity levels. Finally, storing the SP at -20 degrees C decreased (p 0.001) SP-levels of TEAC, PON-1 and GPx, and increased (p 0.01) OSI values. Strong positive relationships (p 0.001) were found between antioxidant SP-levels in processed samples and their respective controls. In sum, handling and SP storage influence antioxidant measurements in AI-boars. Reliable levels of SP-antioxidants can only be warranted if a strict protocol for harvesting and SP storage is followed.

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  • 48.
    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.

  • 49.
    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 1435-165X, Vol. 29, p. 409-411Article in journal (Other academic)
    Abstract [en]

    The original article has been corrected.

  • 50.
    Becerro-Rey, Laura
    et al.
    Univ Extremadura, Spain.
    Martin-Cano, Francisco Eduardo
    Univ Extremadura, Spain.
    Ferrusola, Cristina Ortega
    Univ Extremadura, 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.
    Gaitskell-Phillips, Gemma
    Univ Extremadura, Spain.
    da Silva-Alvarez, Eva
    Univ Extremadura, Spain.
    Silva-Rodriguez, Antonio
    Univ Extremadura, Spain.
    Gil, Maria Cruz
    Univ Extremadura, Spain.
    Pena, Fernando J.
    Univ Extremadura, Spain.
    Aging of stallion spermatozoa stored in vitro is delayed at 22C using a 67 mm glucose-10 mm pyruvate-based media2023In: Andrology, ISSN 2047-2919, E-ISSN 2047-2927Article in journal (Refereed)
    Abstract [en]

    Background: Most commerce of equine seminal doses is carried out using commercial extenders under refrigeration at 5 degrees C.Objectives: To determine if 10 mM pyruvate in a 67 mM glucose extender and storage at 22 degrees C could be the basis of an alternative storage method to cooling to 5 degrees C.Material and methods: Stallion ejaculates were extendedin: INRA96 (67 mM glucose, non-pyruvate control), modified Tyrodes (67 mM glucose-10 mM pyruvate), supplemented with 0, 10, 50, and 100 mu M itaconate. As itaconate was vehiculated in DMSO, a control vehicle was also included. Sperm motility, viability, mitochondrial membrane potential, and production of reactive oxygen species were measured after collection and again after 48 and 96 h of storage at 22 degrees C. To disclose molecular metabolic changes, spermatozoa were incubated up to 3 h in modified Tyrodes 67 mM glucose-10 mM pyruvate and modified Tyrodes 67 mM glucose, and metabolic analysis conducted.Results: After 96 h of storage aliquots stored in the control, INRA96 had a very poor total motility of 5.6% +/- 2.3%, while in the 67 mM glucose-10 mM pyruvate/10 mu M itaconate extender, total motility was 34.7% +/- 3.8% (p = 0.0066). After 96 h, viability was better in most pyruvate-based media, and the mitochondrial membrane potential in spermatozoa extended in INRA96 was relatively lower (p &lt; 0.0001). Metabolomics revealed that in the spermatozoa incubated in the high pyruvate media, there was an increase in the relative amounts of NAD(+), pyruvate, lactate, and ATP.Discussion and conclusions: Aliquots stored in a 67 mM glucose-10 mM pyruvatebased medium supplemented with 10 mu M itaconate, maintained a 35% total motility after 96 h of storage at 22 degrees C, which is considered the minimum acceptable motility for commercialization. Improvements may be related to the conversion of pyruvate to lactate and regeneration of NAD(+).

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