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  • 201.
    Alkner, Björn
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Department of Orthopaedics, Eksjö, Region Jönköping County, Sweden.
    Halvardsson, Christina
    Falun Cent Hosp, Sweden.
    Brakenhielm, Gustaf
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Medicinska fakulteten. Department of Orthopaedics, Eksjö, Region Jönköping County, Sweden.
    Eskilsson, Therese
    Falun Cent Hosp, Sweden.
    Andersson, Erika
    Falun Cent Hosp, Sweden.
    Fritzell, Peter
    Falun and Futurum Acad Hlth and Care, Sweden.
    Effect of postoperative pneumatic compression after volar plate fixation of distal radial fractures: a randomized controlled trial2018Ingår i: Journal of Hand Surgery, European Volume, ISSN 1753-1934, E-ISSN 2043-6289, Vol. 43, nr 8, s. 825-831Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    We investigated the difference between postoperative rehabilitation with or without adjunctive intermittent pneumatic compression therapy following distal radial fracture treated with volar plating. A total of 115 patients were randomized to a control or to an experimental group. After 4 weeks of immobilization the experimental group received intermittent pneumatic compression therapy in addition to conventional postoperative rehabilitation. Primary outcome up to 1 year postoperatively was assessed using the Canadian Occupational Performance Measure. No significant differences between groups were found. There were no clinically relevant differences regarding the secondary outcome measures swelling, strength, pain and flexibility. We conclude that postoperative intermittent pneumatic compression treatment had no major benefits. The results of the present study do not support general use of intermittent pneumatic compression initiated 4 weeks following volar plating surgery for distal radial fracture. Level of evidence: I

  • 202.
    Allan, Douglas W.
    et al.
    University of British Columbia, Canada.
    Thor, Stefan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    Transcriptional selectors, masters, and combinatorial codes: regulatory principles of neural subtype specification2015Ingår i: WILEY INTERDISCIPLINARY REVIEWS-DEVELOPMENTAL BIOLOGY, ISSN 1759-7684, Vol. 4, nr 5, s. 505-528Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    The broad range of tissue and cellular diversity of animals is generated to a large extent by the hierarchical deployment of sequence-specific transcription factors and co-factors (collectively referred to as TFs herein) during development. Our understanding of these developmental processes has been facilitated by the recognition that the activities of many TFs can be meaningfully described by a few functional categories that usefully convey a sense for how the TFs function, and also provides a sense for the regulatory organization of the developmental processes in which they participate. Here, we draw on examples from studies in Caenorhabditis elegans, Drosophila melanogaster, and vertebrates to discuss how the terms spatial selector, temporal selector, tissue/cell type selector, terminal selector and combinatorial code may be usefully applied to categorize the activities of TFs at critical steps of nervous system construction. While we believe that these functional categories are useful for understanding the organizational principles by which TFs direct nervous system construction, we however caution against the assumption that a TFs function can be solely or fully defined by any single functional category. Indeed, most TFs play diverse roles within different functional categories, and their roles can blur the lines we draw between these categories. Regardless, it is our belief that the concepts discussed here are helpful in clarifying the regulatory complexities of nervous system development, and hope they prove useful when interpreting mutant phenotypes, designing future experiments, and programming specific neuronal cell types for use in therapies.

  • 203.
    Allemann, Hanna
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för omvårdnad. Linköpings universitet, Medicinska fakulteten.
    Strömberg, Anna
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för omvårdnad. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Kardiologiska kliniken US. Sue and Bill Gross School of Nursing, University of California Irvine, USA.
    Thylén, Ingela
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för omvårdnad. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Kardiologiska kliniken US.
    Perceived Social Support in Persons With Heart Failure Living With an Implantable Cardioverter Defibrillator: A Cross-sectional Explorative Study2018Ingår i: Journal of Cardiovascular Nursing, ISSN 0889-4655, E-ISSN 1550-5049, Vol. 33, nr 6, s. E1-E8Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: The links between chronic illness, psychological well-being, and social support have previously been established. Social isolation and loneliness have shown an increased mortality risk for those with heart failure (HF). Increasingly more people with HF are living with an implantable cardioverter defibrillator (ICD), but only a few small-scale studies have focused on social support in this population.

    OBJECTIVE: The aim of this study was to explore factors related to perceived social support in a large cohort of individuals with HF living with an ICD.

    METHODS: All eligible adult ICD recipients in the Swedish ICD registry were invited to participate in this cross-sectional study. For this analysis, those with HF and complete data on perceived social support were included (N = 1550; age, 67.3 (SD, 9.8) years; 19.5% female).

    RESULTS: Most reported a high level of social support, but 18% did not. In logistic regression, living alone was the greatest predictor of low/medium support. Lower social support for those living alone was associated with poorer perceived health status, having symptoms of depression, and experiencing low perceived control. For those living with someone, lower support was associated with female gender, symptoms of depression and anxiety, and less control. Heart failure status and perceived symptom severity were not related to the outcome.

    CONCLUSION: One in five participants reported low/medium social support. Our study underlines the complex relationships between perceived social support, psychological well-being and perceived control over the heart condition. Multiple aspects need to be taken into account when developing interventions to provide psychosocial support and optimize outcomes in this patient group.

    Publikationen är tillgänglig i fulltext från 2019-12-01 11:28
  • 204.
    Allemann, Hanna
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för omvårdnad. Linköpings universitet, Medicinska fakulteten.
    Sund-Levander, Märta
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för omvårdnad. Linköpings universitet, Medicinska fakulteten.
    Nurses' actions in response to nursing assistants' observations of signs and symptoms of infections among nursing home residents2015Ingår i: Nursing Open, ISSN 2054-1058, Vol. 2, nr 3, s. 97-104Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Aims

    To describe what nurses do during episodes of suspected infection in elderly nursing home residents and if these actions are linked to who is initiating an episode and whether the episode is considered an infection or not.

    Design

    Prospective descriptive study. Data were collected in 2008–2010.

    Methods

    Summarized and categorized documentation by nursing assistants and nurses was used for summative content analysis.

    Results

    Nurses' actions seem to be related to who initiated the episode and if the episodes are categorized as ‘non-infection’, ‘possible infection’ or ‘infection’. Actions could be ‘observation’, ‘screenings’, ‘engaged in waiting’, ‘follow-ups’, ‘nurse-prescribed actions’, ‘diagnosing’, ‘contacting the physician’, ‘carrying out an action prescribed by the physician’, ‘contacting an ambulance or arranging an emergency visit to the hospital’ and ‘prescribing screening’. As NAs often initiate episodes of suspected infection by observing changed conditions, it seems important to include the NA in the decision-making process as these observations could detect possible early signs and symptoms of infections.

  • 205.
    Allemann, Hanna
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för omvårdnad. Linköpings universitet, Medicinska fakulteten.
    Thylén, Ingela
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för omvårdnad. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Kardiologiska kliniken US.
    Ågren, Susanna
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för omvårdnad. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Thorax-kärlkliniken i Östergötland.
    Liljeroos, Maria
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för omvårdnad. Linköpings universitet, Medicinska fakulteten. Uppsala Univ, Sweden.
    Strömberg, Anna
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för omvårdnad. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Kardiologiska kliniken US.
    Perceptions of Information and Communication Technology as Support for Family Members of Persons With Heart Failure: Qualitative Study2019Ingår i: Journal of Medical Internet Research, ISSN 1438-8871, E-ISSN 1438-8871, Vol. 21, nr 7, artikel-id e13521Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Heart failure (HF) affects not only the person diagnosed with the syndrome but also family members, who often have the role of informal carers. The needs of these carers are not always met, and information and communications technology (ICT) could have the potential to support them in their everyday life. However, knowledge is lacking about how family members perceive ICT and see opportunities for this technology to support them. Objective: The aim of this study was to explore the perceptions of ICT solutions as supportive aids among family members of persons with HF. Methods: A qualitative design was applied. A total of 8 focus groups, comprising 23 family members of persons affected by HF, were conducted between March 2015 and January 2017. Participants were recruited from 1 hospital in Sweden. A purposeful sampling strategy was used to find family members of persons with symptomatic HF from diverse backgrounds. Data were analyzed using qualitative content analysis. Results: The analysis revealed 4 categories and 9 subcategories. The first category, about how ICT could provide relevant support, included descriptions of how ICT could be used for communication with health care personnel, for information and communication retrieval, plus opportunities to interact with persons in similar life situations and to share support with peers and extended family. The second category, about how ICT could provide access, entailed how ICT could offer solutions not bound by time or place and how it could be both timely and adaptable to different life situations. ICT could also provide an arena for family members to which they might not otherwise have had access. The third category concerned how ICT could be too impersonal and how it could entail limited personal interaction and individualization, which could lead to concerns about usability. It was emphasized that ICT could not replace physical meetings. The fourth category considered how ICT could be out of scope, reflecting the fact that some family members were generally uninterested in ICT and had difficulties envisioning how it could be used for support. It was also discussed as more of a solution for the future. Conclusions: Family members described multiple uses for ICT and agreed that ICT could provide access to relevant sources of information from which family members could potentially exchange support. ICT was also considered to have its limitations and was out of scope for some but with expected use in the future. Even though some family members seemed hesitant about ICT solutions in general, this might not mean they are unreceptive to suggestions about their usage in, for example, health care. Thus, a variety of factors should be considered to facilitate future implementations of ICT tools in clinical practice.

  • 206.
    Allvin, Renée
    et al.
    Clinical Skills Centre, Faculty of Medicine and Health, School of Medical Sciences, Örebro University, Örebro.
    Berndtzon, Magnus
    Metodikum - Skill Centre of Medical Simulation Region County Jönköping, Jönköping.
    Carlzon, Liisa
    Simulation Centre West, Department of Research, Education and Development, Sahlgrenska University Hospital, Gothenburg.
    Edelbring, Samuel
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för samhällsmedicin. Linköpings universitet, Medicinska fakulteten. Department of Learning, Informatics, Management and Ethics, Karolinska Institutet, Stockholm.
    Hult, Håkan
    Linköpings universitet, Institutionen för medicin och hälsa. Linköpings universitet, Medicinska fakulteten.
    Hultin, Magnus
    Department of Surgical and Perioperative Sciences, Anaesthesiology and Intensive Care, Medical Faculty, Umeå University, Umeå.
    Karlgren, Klas
    Department of Learning, Informatics, Management and Ethics, Karolinska Institutet, Stockholm; Department of Research, Education and Development and Innovation, Södersjukhuset Hospital, Stockholm.
    Masiello, Italo
    Department of Clinical Science and Education, Karolinska Institutet, Södersjukhuset Hospital, Stockholm.
    Södersved Källestedt, Marie-Louise
    Clinical Skills Centre, Centre for Clinical Research, Uppsala University, Västerås.
    Tamás, Éva
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Thorax-kärlkliniken i Östergötland.
    Confident but not theoretically grounded: experienced simulation educators perceptions of their own professional development2017Ingår i: Advances in Medical Education and Practice, ISSN 1179-7258, E-ISSN 1179-7258, Vol. 8, s. 99-108Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Medical simulation enables the design of learning activities for competency areas (eg, communication and leadership) identified as crucial for future health care professionals. Simulation educators and medical teachers follow different career paths, and their education backgrounds and teaching contexts may be very different in a simulation setting. Although they have a key role in facilitating learning, information on the continuing professional development (pedagogical development) of simulation educators is not available in the literature.

    Objectives: To explore changes in experienced simulation educators’ perceptions of their own teaching skills, practices, and understanding of teaching over time.

    Methods: A qualitative exploratory study. Fourteen experienced simulation educators participated in individual open-ended interviews focusing on their development as simulation educators. Data were analyzed using an inductive thematic analysis.

    Results: Marked educator development was discerned over time, expressed mainly in an altered way of thinking and acting. Five themes were identified: shifting focus, from following to utilizing a structure, setting goals, application of technology, and alignment with profession. Being confident in the role as an instructor seemed to constitute a foundation for the instructor’s pedagogical development.

    Conclusion: Experienced simulation educators’ pedagogical development was based on self-confidence in the educator role, and not on a deeper theoretical understanding of teaching and learning. This is the first clue to gain increased understanding regarding educational level and possible education needs among simulation educators, and it might generate several lines of research for further studies.

  • 207.
    Almberg, Maria
    et al.
    Mobil Centre Gothenburg, Sweden.
    Selander, Helena
    Mobil Centre Gothenburg, Sweden; University of Gothenburg, Sweden.
    Falkmer, Marita
    Curtin University, Australia; Jonköping University, Sweden.
    Vaz, Sharmila
    Curtin University, Australia.
    Ciccarelli, Marina
    Curtin University, Australia.
    Falkmer, Torbjörn
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för samhällsmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Smärt och rehabiliteringscentrum. Curtin University, Australia.
    Experiences of facilitators or barriers in driving education from learner and novice drivers with ADHD or ASD and their driving instructors2017Ingår i: Developmental Neurorehabilitation, ISSN 1751-8423, E-ISSN 1751-8431, Vol. 20, nr 2, s. 59-67Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Little is known about whether individuals with autism spectrum disorder (ASD) or attention deficit hyperactive disorder (ADHD) experience any specific facilitators or barriers to driving education. Objective: To explore the facilitators or barriers to driving education experienced by individuals with ASD or ADHD who obtained a learners permit, from the perspective of the learner drivers and their driving instructors. Methods: Datawere collected from33 participants with ASD or ADHD, and nine of their driving instructors. Results: Participants with ASD required twice asmany driving lessons andmore on-road tests than those with ADHD. Participants with ADHD repeated the written tests more than those with ASD. Driving license theory was more challenging for individuals with ADHD, whilst individuals with ASD found translating theory into practice and adjusting to "unfamiliar driving situations to be the greatest challenges. Conclusion: Obtaining a driving license was associated with stressful training experience.

  • 208.
    Almborg, Ann-Helen
    et al.
    National Board of Health and Welfare, Stockholm, Sweden / Jönköping University, Jönköping Academy, Sweden.
    Haglund, Lena
    Linköpings universitet, Institutionen för samhälls- och välfärdsstudier, Avdelningen för arbetsterapi. Linköpings universitet, Medicinska fakulteten.
    KVÅ och ICHI med fokus på arbetsterapi2019Konferensbidrag (Refereegranskat)
    Abstract [sv]

    Bakgrund/Syfte*

    Inom WHO pågår ett utvecklingsarbete av en ny klassifikation av åtgärder ”International Classification of Health Interventions” (ICHI), som kompletterar ICF och ICD. WHO har pågående tester av ICHI. Socialstyrelsen och nordiska klassifikationscentret har genomfört ett antal tester bland annat omfattande arbetsterapiåtgärder inom psykiatrin. Åtgärder dokumenteras med Klassifikation av vårdåtgärder (KVÅ) inom hälso- och sjukvård i Sverige.

    Syfte var att mappa ett antal KVÅ-åtgärder som tillämpas inom psykiatrisk arbetsterapi till ICHI.

    Metod/Tillvägagångssätt*

    En lista med åtgärder inom psykiatri, som används av arbetsterapeuter från sex olika sjukhus i Sverige mappades till ICHI 2018. Mappningsregler för ICHI användes där grad av samstämmighet värderas. Även kardinalitet dvs. hur många ICHI-interventioner användes för att beskriva KVÅ-åtgärden. Resultatet bearbetades med deskriptiv statistik.

    Resultat/Preliminärt resultat*

    Totalt mappades 136 KVÅ-åtgärder (27 undersökande, 98 behandlande och 11 administrativa). Kardinaliteten mellan KVÅ och ICHI varierade från 1:0 till 1:28. Nio procent av KVÅ-åtgärderna kunde inte mappas till ICHI (1:0). I 37 procent var förhållandet 1:1, dvs en KVÅ-åtgärd mappades till en ICHI-intervention. I 34 procent var förhållandet 1:2 eller 1:3 och i 17 procent mellan 1:4-1:9. Fyra KVÅ-åtgärder hade förhållandet 1:14, 1:25 och 1:28. Grad av samstämmighet mellan KVÅ-åtgärd och ICHI-intervention visade att 14 procent överensstämde exakt. 67 procent av KVÅ-åtgärderna var bredare dvs. mindre specifika än ICHI-interventionerna och 18 procent av KVÅ-åtgärderna var mer specifika än ICHI-intervention.

    Slutsats/Praktisk tillämpning*

    ICHI har fler specifika interventioner för att dokumentera arbetsterapeuters åtgärder inom psykiatrisk verksamhet än KVÅ. Att börja tillämpa ICHI inom svenska psykiatrisk arbetsterapiverksamhet skulle öka kvalitén på dokumentationen.

  • 209.
    Almborg, Ann-Helen
    et al.
    Jönköpings Högskola, Socialstyrelsen.
    Haglund, Lena
    Linköpings universitet, Institutionen för samhälls- och välfärdsstudier, Avdelningen för arbetsterapi. Linköpings universitet, Medicinska fakulteten.
    Mapping Swedish mental health interventions to ICHI: occupational therapy perspective2018Konferensbidrag (Övrigt vetenskapligt)
  • 210.
    Almby, Kristina
    et al.
    Uppsala Univ, Sweden.
    Edholm, David
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Kirurgiska kliniken US.
    Anastomotic Strictures After Roux-en-Y Gastric Bypass: a Cohort Study from the Scandinavian Obesity Surgery Registry2019Ingår i: Obesity Surgery, ISSN 0960-8923, E-ISSN 1708-0428, Vol. 29, nr 1, s. 172-177Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BackgroundRoux-en-Y gastric bypass (RYGB) is the most common bariatric procedure worldwide. Anastomotic stricture is a known complication of RYGB. The aim was to explore the incidence and outcomes of strictures within the Scandinavian Obesity Surgery Registry (SOReg).MethodSOReg included prospective data from 36,362 patients undergoing bariatric surgery in the years 2007-2013. Outcomes were recorded at 30-day and at 1-year follow-up according to the standard SOReg routine. The medical charts of patients suffering from stricture after RYGB were requested and assessed.SettingNational bariatric surgery registryResultsAnastomotic stricture within 1year of surgery was confirmed in 101 patients representing an incidence of 0.3%. Risk factors for stricture were patient age above 60years (odds ratio (OR), 6.2 95% confidence interval (CI) 2.7-14.3), circular stapled gastrojejunostomy (OR 2.7, 95% CI 1.4-5.5), postoperative anastomotic leak (OR 8.9 95%, CI 4.7-17.0), and marginal ulcer (OR 30.0, 95% CI 19.2-47.0). Seventy-five percent of the strictures were diagnosed within 70days of surgery. Two dilatations or less was sufficient to successfully treat 50% of patients. Ten pecent of patients developed perforation during dilatation, and the risk of perforating at each dilatation was 3.8%. Perforation required surgery in six cases but there was no mortality. Strictures in SOReg may be underreported, which could explain the low incidence in the study.ConclusionMost strictures present within 2months and are successfully treated with two dilatations or less. Dilating a strictured gastrojejunostomy entails a risk of perforation (3.8%).

  • 211.
    Almeida, Nuno
    et al.
    Katholieke University of Leuven, Belgium; GE Vingmed Ultrasound AS, Norway.
    Papachristidis, Alexandros
    Kings Coll Hospital London, England.
    Pearson, Peter
    Kings Coll Hospital London, England.
    Imre Sarvari, Sebastian
    University of Oslo, Norway.
    Engvall, Jan
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Fysiologiska kliniken US. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV.
    Edvardsen, Thor
    University of Oslo, Norway.
    Monaghan, Mark
    Kings Coll Hospital London, England.
    Gerard, Olivier
    GE Vingmed Ultrasound AS, Norway.
    Samset, Eigil
    GE Vingmed Ultrasound AS, Norway; University of Oslo, Norway.
    Dhooge, Jan
    Katholieke University of Leuven, Belgium.
    Left atrial volumetric assessment using a novel automated framework for 3D echocardiography: a multi-centre analysis2017Ingår i: European Heart Journal Cardiovascular Imaging, ISSN 2047-2404, E-ISSN 2047-2412, Vol. 18, nr 9, s. 1008-1015Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Aims This study aims at validating a software tool for automated segmentation and quantification of the left atrium (LA) from 3D echocardiography. Methods and results The LA segmentation tool uses a dual-chamber model of the left side of the heart to automatically detect and track the atrio-ventricular plane and the LA endocardium in transthoracic 3D echocardiography. The tool was tested in a dataset of 121 ultrasound images from patients with several cardiovascular pathologies (in a multi-centre setting), and the resulting volumes were compared with those assessed manually by experts in a blinded analysis using conventional contouring. Bland-Altman analysis showed good agreement between the automated method and the manual references, with differences (mean +/- 1.96 SD) of 0.5 +/- 5.7 mL for LA minimum volume and -1.6 +/- 9.7 mL for LA maximum volume (comparable to the inter-observer variability of manual tracings). The automated tool required no user interaction in 93% of the recordings, while 4% required a single click and only 2% required contour adjustments, reducing considerably the amount of time and effort required for LA volumetric analysis. Conclusion The automated tool was validated in a multi-centre setting, providing quantification of the LA volume over the cardiac cycle with minimal user interaction. The results of the automated analysis were in agreement with those estimated manually by experts. This study shows that such approach has clinical utility for the assessment of the LA morphology and function, automating and facilitating the time-consuming task of analysing 3D echocardiographic recordings.

  • 212.
    Almroth, Gabriel
    et al.
    Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Njurmedicinska kliniken US. Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för läkemedelsforskning.
    Lönn, Johanna
    Örebro Universitet, Sweden.
    Uhlin, Fredrik
    Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Njurmedicinska kliniken US. Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för läkemedelsforskning.
    Brudin, Lars
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Department of Physiology, County Hospital, Kalmar, Sweden.
    Andersson, Bengt Andersson
    Sahlgrenska University Hospital, Göteborg, Sweden.
    Hahn-Zoric, Mirjana
    Sahlgrenska University Hospital, Göteborg, Sweden.
    Sclerostin, TNF-alpha and Interleukin-18 Correlate and are Together with Klotho Related to Other Growth Factors and Cytokines in Haemodialysis Patients2016Ingår i: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 83, nr 1, s. 58-63Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Patients with chronic renal failure are known to have renal osteodystrophy (bone disease) and increased calcification of vessels. A new marker of bone disease, sclerostin, the two pro-inflammatory cytokines tumour necrosis factor-alpha (TNF-alpha) and interleukin-18 (IL-18), and the fibroblast growth factor-23 (FGF-23) receptor-associated marker Klotho were tested in 84 haemodialysis (HD) patients and in healthy controls. The patients had significantly higher levels of the three former markers than of the controls while Klotho was significantly higher in the controls. Low level, but significant, correlations were observed in the patient group when the levels of these four markers were compared to each other and to those of 5 cytokines and growth factors tested earlier; high-sensitive CRP (hsCRP), interleukin-6 (IL-6), hepatocyte growth factor (HGF), fibroblast growth factor-23 (FGF-23) and soluble urokinase plasminogen activator (suPAR). Ln sclerostin correlated positively to Ln hsTNF-alpha, Ln HGF and Ln suPAR. Ln hsTNF-alpha correlated positively to Ln sclerostin, Ln hsCRP, Ln IL-6, Ln FGF-23, Ln suPAR and Ln IL-18. Ln IL-18 correlated positively to Ln suPAR and Ln TNF-alpha. Ln Klotho correlated negatively to Ln hsCRP but did not correlate to Ln FGF-23. The markers studied here may be involved in the calcification of vessels seen in HD patients due to a combination of inflammation and bone disease. The mechanisms are still not fully known but may be of importance for future therapeutic possibilities in this group of patients.

  • 213.
    Almroth, Gabriel
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Njurmedicinska kliniken US.
    Sjöberg, Folke
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Hand- och plastikkirurgiska kliniken US.
    Recidivating thrombocytopenia, renal failure and thymitis2017Ingår i: Recidivating thrombocytopenia, renal failure and thymitis, 2017Konferensbidrag (Övrigt vetenskapligt)
  • 214.
    Almroth, Gabriel
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Njurmedicinska kliniken US.
    Sjöberg, Folke
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Hand- och plastikkirurgiska kliniken US.
    Recurrent thrombocytopenia, renal failure and thymitis of unknown cause. A case report2017Ingår i: Vaskulär medicin, Vol. 33, nr 3, s. 24-25Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    A 45-year old man was admitted to an intensive care unit with flank pain and thrombocytopenia. He was treated for a suspected septicaemia but turned out to have signs of an unknown collagenosis which responded to plasma exchange, thymectomi and corticosteroids. Kidney biopsy revealed an intense tubulointerstitial reaction with suspected microthrombotic lesions in the vessels. The condition reoccurred with thrombocytopenia a couple of months later but responded to plasma exchange, corticosteroids and mycophenolate mofetil. An unknown collagenosis with findings of autoimmune thymitis and tubulointerstitial nephritis is the most probable cause of the condition.

  • 215.
    Alonso, Fabiola
    et al.
    Linköpings universitet, Institutionen för medicinsk teknik, Biomedicinsk instrumentteknik. Linköpings universitet, Tekniska fakulteten.
    Latorre, Malcolm
    Linköpings universitet, Institutionen för medicinsk teknik, Biomedicinsk instrumentteknik. Linköpings universitet, Tekniska fakulteten.
    Göransson, Nathanael
    Linköpings universitet, Institutionen för medicinsk teknik. Linköpings universitet, Tekniska fakulteten. Region Östergötland, Sinnescentrum, Neurokirurgiska kliniken US.
    Zsigmond, Peter
    Region Östergötland, Sinnescentrum, Neurokirurgiska kliniken US. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Wårdell, Karin
    Linköpings universitet, Institutionen för medicinsk teknik, Biomedicinsk instrumentteknik. Linköpings universitet, Tekniska fakulteten.
    Investigation into Deep Brain Stimulation Lead Designs: A Patient-Specific Simulation Study2016Ingår i: Brain Sciences, ISSN 2076-3425, E-ISSN 2076-3425, Vol. 6, nr 3, s. 1-16Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    New deep brain stimulation (DBS) electrode designs offer operation in voltage and current mode and capability to steer the electric field (EF). The aim of the study was to compare the EF distributions of four DBS leads at equivalent amplitudes (3 V and 3.4 mA). Finite element method (FEM) simulations (n = 38) around cylindrical contacts (leads 3389, 6148) or equivalent contact configurations (leads 6180, SureStim1) were performed using homogeneous and patient-specific (heterogeneous) brain tissue models. Steering effects of 6180 and SureStim1 were compared with symmetric stimulation fields. To make relative comparisons between simulations, an EF isolevel of 0.2 V/mm was chosen based on neuron model simulations (n = 832) applied before EF visualization and comparisons. The simulations show that the EF distribution is largely influenced by the heterogeneity of the tissue, and the operating mode. Equivalent contact configurations result in similar EF distributions. In steering configurations, larger EF volumes were achieved in current mode using equivalent amplitudes. The methodology was demonstrated in a patient-specific simulation around the zona incerta and a “virtual” ventral intermediate nucleus target. In conclusion, lead design differences are enhanced when using patient-specific tissue models and current stimulation mode.

  • 216.
    Alonso, Fabiola
    et al.
    Linköpings universitet, Institutionen för medicinsk teknik, Avdelningen för medicinsk teknik. Linköpings universitet, Tekniska fakulteten.
    Zsigmond, Peter
    Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Kirurgiska kliniken US. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Neurokirurgiska kliniken US.
    Wårdell, Karin
    Linköpings universitet, Institutionen för medicinsk teknik, Avdelningen för medicinsk teknik. Linköpings universitet, Tekniska fakulteten.
    Influence of Virchow-Robin spaces in the Electric Field Distribution in Subthalamic Nucleus Deep Brain Stimulation2019Konferensbidrag (Refereegranskat)
    Abstract [en]

    Objectives: Previous investigations have shown the appearance of cysts i.e. Virchow-Robin spaces (VR) in the basal ganglia and their relationship with parkinsonian symptoms [1-3]. Simulations [4]using the finite element method (FEM) suggests that VR affects the electric field around deep brain stimulation (DBS) electrodes. The aim of the study was to evaluate how the electric field is modified by the presence of cysts in the STN. Methods: The effect of cysts on the electric field around the DBS lead placed in the STN was evaluated using FEM. 3D patient-specific brain models were built with COMSOL 5.2 (COMSOL AB, Sweden) and an in-house developed software [5] to convert a T2 weighted MRI of Parkinsonian patients (ethics approval no: 2012/434-3) into electrical conductivity matrix readable by FEM software. VR was classified as CSF [6]assigning a high electrical conductivity (2.0 S/m). The stimulation amplitudes were set to the clinically programmed values. Depending on the lead used, the stimulation was set to voltage control (3389) or current control (6180, ring mode). The coordinates corresponding to the lowest (first) electrode and the third higher up in the lead, taken from the postoperative CT electrode artefact, were used to localize the leads in the brain model [7]. The electric field was visualized with a 0.2V/mm isosurface. Results: Simulations showed that the electric field distribution is affected by the cysts. The higher conductivity at these regions in the vicinity of the electrode redistributes the electric field pushing it away from the cyst. The same effect occurs regardless of the operating mode or the lead design as long as the directional lead is configured in ring mode. Conclusions: The use of patient-specific models has shown the importance of considering nuances of the patients’ anatomy in the STN. This information can be used to determine the stimulation parameter and to support the analysis of side effects induced by the stimulation. The potential advantage of directional leads can also be assessed by including in the model patient-specific data.

  • 217.
    Alonso, Juan-Manuel
    et al.
    Int Assoc Athlet Federat, Med & Antidoping Commiss, Monaco, Monaco; Qatar Orthoped & Sports Med Hosp, Sports Med Dept, Aspetar, Doha, Qatar.
    Jacobsson, Jenny
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för samhällsmedicin. Linköpings universitet, Medicinska fakulteten.
    Timpka, Toomas
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för samhällsmedicin. Linköpings universitet, Hälsouniversitetet. Region Östergötland, Centrum för hälso- och vårdutveckling, Folkhälsocentrum.
    Ronsen, Ola
    Int Assoc Athlet Federat, Med & Antidoping Commiss, Monaco, Monaco; Aker Solut, Lysaker, Norway.
    Kajenienne, Alma
    Int Assoc Athlet Federat, Med & Antidoping Commiss, Monaco, Monaco; Lithuanian Univ Hlth Sci, Inst Sport, Kaunas, Lithuania.
    Dahlström, Örjan
    Linköpings universitet, Institutionen för beteendevetenskap och lärande, Handikappvetenskap. Linköpings universitet, Filosofiska fakulteten. Linköpings universitet, Institutionen för beteendevetenskap, Institutet för handikappvetenskap, IHV.
    Spreco, Armin
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för samhällsmedicin. Linköpings universitet, Hälsouniversitetet.
    Edouard, Pascal
    Univ Hosp St Etienne, Fac Med, Sports Med Unity, Dept Clin & Exercise Physiol, St Etienne, France; Univ Lyon, Exercise Physiol Lab, LPE EA 4338, St Etienne, France; French Athlet Federat, Med Commiss, Paris, France.
    Preparticipation injury complaint is a risk factor for injury: a prospective study of the Moscow 2013 IAAF Championships.2015Ingår i: British Journal of Sports Medicine, ISSN 0306-3674, E-ISSN 1473-0480, Vol. 49, nr 17, s. 1118-U45Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVES: To determine the health status of athletes before the start of an international athletics championship and to determine whether preparticipation risk factors predicted in-championship injuries.

    METHODS: At the beginning of the 2013 International Association of Athletics Federations (IAAF) World Championships, all registered athletes (n=1784) were invited to complete a preparticipation health questionnaire (PHQ) on health status during the month preceding the championships. New injuries that occurred at the championships were prospectively recorded.

    RESULTS: The PHQ was completed by 698 (39%) athletes; 204 (29.2%) reported an injury complaint during the month before the championships. The most common mode of onset of preparticipation injury complaints was gradual (43.6%). Forty-nine athletes in the study reported at least one injury during the championships. Athletes who reported a preparticipation injury complaint were at twofold increased risk for an in-championship injury (OR=2.09; 95% CI 1.16 to 3.77); p=0.014). Those who reported a preparticipation gradual-onset injury complaint were at an almost fourfold increased risk for an in-championship time-loss injury (OR=3.92; 95% CI 1.69 to 9.08); p=0.001). Importantly, the preparticipation injury complaint severity score was associated with the risk of sustaining an in-championship injury (OR=1.14; 95% CI 1.06 to 1.22); p=0.001).

    SUMMARY AND CONCLUSIONS: About one-third of the athletes participating in the study reported an injury complaint during the month before the championships, which represented a risk factor for sustaining an injury during the championship. This study emphasises the importance of the PHQ as a screening tool to identify athletes at risk of injuries before international championships.

  • 218.
    Alping, Peter
    et al.
    Karolinska Inst, Sweden.
    Piehl, Fredrik
    Karolinska Inst, Sweden; Stockholm Hlth Serv, Sweden; Karolinska Univ Hosp, Sweden.
    Langer-Gould, Annette
    Kaiser Permanente, CA USA; Kaiser Permanente, CA USA.
    Frisell, Thomas
    Karolinska Inst, Sweden.
    Burman, Joachim
    Uppsala Univ, Sweden.
    Fink, Katharina
    Karolinska Inst, Sweden.
    Fogdell-Hahn, Anna
    Karolinska Inst, Sweden.
    Gunnarsson, Martin
    Orebro Univ, Sweden.
    Hillert, Jan
    Karolinska Inst, Sweden.
    Kockum, Ingrid
    Stockholm Hlth Serv, Sweden.
    Lycke, Jan
    Univ Gothenburg, Sweden.
    Nilsson, Petra
    Lund Univ, Sweden.
    Olsson, Tomas
    Karolinska Inst, Sweden.
    Salzer, Jonatan
    Umea Univ, Sweden.
    Svenningsson, Anders
    Danderyd Hosp, Sweden.
    Virtanen, Suvi
    Karolinska Inst, Sweden.
    Vrethem, Magnus
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Närsjukvården i centrala Östergötland, Neurologiska kliniken.
    Validation of the Swedish Multiple Sclerosis Register Further Improving a Resource for Pharmacoepidemiologic Evaluations2019Ingår i: Epidemiology, ISSN 1044-3983, E-ISSN 1531-5487, Vol. 30, nr 2, s. 230-233Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The Swedish Multiple Sclerosis Register is a national register monitoring treatment and clinical course for all Swedish multiple sclerosis (MS) patients, with high coverage and close integration with the clinic. Despite its great value for epidemiologic research, it has not previously been validated. In this brief report, we summarize a large validation of amp;gt;3,000 patients in the register using clinical chart review in the context of the COMBAT-MS study. While further improving the data quality for a central cohort of patients available for future epidemiologic research, this study also allowed us to estimate the accuracy and completeness of the register data.

  • 219.
    Alstad, V.
    et al.
    Department of Oral and Maxillofacial Surgery, Karolinska University Hospital, Stockholm, Sweden.
    Abtahi, Jahan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Käkkliniken US.
    Surgical removal of keratocystic odontogenic tumours via a Le Fort I osteotomy approach: a retrospective study of the recurrence rate2017Ingår i: International Journal of Oral and Maxillofacial Surgery, ISSN 0901-5027, E-ISSN 1399-0020, Vol. 46, nr 4, s. 6s. 434-439Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The keratocystic odontogenic tumour (KCOT) is one of the most aggressive odontogenic cysts and has a high recurrence rate. The treatment of these tumours is the subject of debate. A KCOT in the posterior maxilla with sinus involvement is rare. Few reports have been published in the literature. The purpose of this study was to evaluate the recurrence rate after surgical removal of maxillary KCOTs via a Le Fort I osteotomy. A search was performed to identify patients with a follow-up time of at least 5 years. Nine patients were included in the study. The following clinical variables were analyzed: age at surgery, sex, symptoms, site and size of the tumour, surgical approach, and recurrence rate. The surgical approaches were curettage (n=6) and enucleation (n=3). Recurrence was seen in three patients (33%); all had multilocular tumours. No recurrence was seen in patients with unilocular tumours. The Le Fort I osteotomy approach allows direct visualization and ensures wide excision, minimizing the risk of recurrence. In this series, cases with a multilocular KCOT showed a higher risk of recurrence due to the difficulty of removing the tumour in total. All recurrences took place within 2 years of the intervention; a 5-year follow-up is recommended.

  • 220.
    Alvarez-Rodriguez, Manuel
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten. Univ Autonoma Barcelona, Spain.
    Alvarez, M.
    Univ Leon, Spain.
    Anel-Lopez, L.
    Univ Leon, Spain.
    Guerra, C.
    Univ Leon, Spain.
    Chamorro, C. A.
    Univ Leon, Spain.
    Anel, L.
    Univ Leon, Spain.
    de Paz, P.
    Univ Leon, Spain.
    Martinez-Pastor, F.
    Univ Leon, Spain.
    Effect of length of time post-mortem on quality and freezing capacity of Cantabric chamois (Rupicapra pyrenaica parva) epididymal spermatozoa2018Ingår i: Animal Reproduction Science, ISSN 0378-4320, E-ISSN 1873-2232, Vol. 198, s. 184-192Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Genome Resource Banks are keystones in the ex-situ conservation of wild species. Post-mortem (PM) collection of epididymal spermatozoa is an opportunistic and valuable source of germplasm, the time from the death of the animal limits its use. Seeking to improve germplasm preservation strategies for the chamois (Rupicapra sp.), the effect of PM time on epididymal sperm quality and freezability was studied using the Cantabrian chamois. Samples were classified according to PM collection time, up to 216 h (refrigerated), and cryopreserved (Tris-citric acid-fructose, 430 mOsm/kg, 15% egg yolk, 8% glycerol; freezing at - 20 degrees C/min). Sperm quality was assessed after recovery and post-thawing (motility by CASA, HOS test, abnormal forms, cytoplasmic droplets, and viability and acrosomal damage by flow cytometry). The sperm mass pH and osmolality showed a positive correlation with time. Total sperm motility dropped after 2 days PM, with progressivity and sperm velocities remained similar up to 3 days PM. Sperm freezability was acceptable, with the post-thawing HOST, motility, progressivity, VAP, VCL, VSL and BCF negatively correlating with PM time. Overall, chamois epidydimal samples were not adequate for preservation after 6 days PM. Freezability capacity could make these spermatozoa suitable for specific ART even if kept refrigerated for several days PM.

  • 221.
    Alvarez-Rodriguez, Manuel
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten.
    Alvarez, M.
    University of Leon, Spain.
    Anel-Lopez, L.
    SaBio IREC CSIC UCLM JCCM, Spain.
    Lopez-Uruena, E.
    University of Leon, Spain.
    Manrique, P.
    University of Leon, Spain.
    Borragan, S.
    Cabarceno Pk, Spain.
    Morrell, J. M.
    Swedish University of Agriculture Science SLU, Sweden.
    de Paz, P.
    University of Leon, Spain.
    Anel, L.
    University of Leon, Spain.
    Effect of colloid (Androcoll-Bear, Percoll, and PureSperm) selection on the freezability of brown bear (Ursus arctos) sperm2016Ingår i: Theriogenology, ISSN 0093-691X, E-ISSN 1879-3231, Vol. 85, nr 6, s. 1097-1105Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The development of a species-specific conservation protocol that involves artificial insemination with frozen semen needs to validate an effective methodology for freezing semen. Colloid centrifugation has been suggested and widely applied as an effective tool for selecting animal spermatozoa for artificial breeding. The objective of the present study was to compare different methods of centrifugation, single layer using Androcoll-Bear and Percoll and double layer using PureSperm 100 (in two different discontinuous gradients 40%-80% and 45%-90%), for the selection of fresh brown bear sperm samples. In the before freezing group, all selected samples showed a higher progressive motility and viability (except Percoll for motility 43.0 +/- 5.3 [P < 0.051); all colloids except PureSperm 45/90% rendered samples with fewer damaged acrosomes. In the after thawing group, all tested centrifugation colloids showed a good capacity to decrease the number of damaged acrosomes. Furthermore, PureSperm treatment (45/90%) resulted in an increase in apoptotic-like changes not only immediately after thawing but also after the incubation test, leading us to suggest that this gradient could induce some kind of deleterious effects on the sperm samples. On the other hand, PureSperm treatment (40/80%) yielded a quality preservation capacity similar to Androcoll-Bear in number of damaged acrosomes, different relative to the control (control, 5.3 +/- 0.6; PureSperm 80, 2.0 +/- 0.3; Androcoll, 2.1 +/- 0.9 [P < 0.051) but a decrease in the number of viable spermatozoa recovered after thawing relative to the control (control, 21.2 +/- 3.1; PureSperm 80, 13.7 +/- 2.7 [P < 0.051). In conclusion, Androcoll-Bear constitutes a useful tool for handling of brown bear ejaculates owing to its simple handling and procedure with a reliable sperm selection and freezability. This colloid yielded an improvement in several sperm parameters in brown bear frozen-thawed semen; the selected spermatozoa of fresh samples with this colloid showed a better resistance to freezing compared with the control sample not only for motility but also for viability. (C) 2016 Elsevier Inc. All rights reserved.

  • 222.
    Alvarez-Rodriguez, Manuel
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten.
    Atikuzzaman, Mohammad
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Medicinska fakulteten. Department of Surgery and Theriogenology, Faculty of Veterinary Animal and Biomedical Sciences, Sylhet Agricultural University, Sylhet, Bangladesh.
    Venhoranta, Heli
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Medicinska fakulteten. University of Helsinki, Department of Production Animal Medicine, Faculty of Veterinary Medicine, Saari, Finland.
    Wright, Dominic
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biologi. Linköpings universitet, Tekniska fakulteten.
    Rodriguez-Martinez, Heriberto
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten.
    Expression of Immune Regulatory Genes in the Porcine Internal Genital Tract Is Differentially Triggered by Spermatozoa and Seminal Plasma2019Ingår i: International Journal of Molecular Sciences, ISSN 1422-0067, E-ISSN 1422-0067, Vol. 20, nr 3, artikel-id 513Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Mating or cervical deposition of spermatozoa or seminal plasma (SP) modifies the expression of genes affecting local immune defense processes at the oviductal sperm reservoir in animals with internal fertilization, frequently by down-regulation. Such responses may occur alongside sperm transport to or even beyond the reservoir. Here, immune-related gene expression was explored with cDNA microarrays on porcine cervix-to-infundibulum tissues, pre-/peri-ovulation. Samples were collected 24 h post-mating or cervical deposition of sperm-peak spermatozoa or SP (from the sperm-peak fraction or the whole ejaculate). All treatments of this interventional study affected gene expression. The concerted action of spermatozoa and SP down-regulated chemokine and cytokine (P00031), interferon-gamma signaling (P00035), and JAK/STAT (P00038) pathways in segments up to the sperm reservoir (utero-tubal junction (UTJ)/isthmus). Spermatozoa in the vanguard sperm-peak fraction (P1-AI), uniquely displayed an up-regulatory effect on these pathways in the ampulla and infundibulum. Sperm-free SP, on the other hand, did not lead to major effects on gene expression, despite the clinical notion that SP mitigates reactivity by the female immune system after mating or artificial insemination.

  • 223.
    Alvarez-Rodriguez, Manuel
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten. Univ Autonoma Barcelona, Spain.
    Lopez-Bejar, Manel
    Univ Autonoma Barcelona, Spain.
    Rodriguez-Martinez, Heriberto
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten.
    The risk of using monoclonal or polyclonal commercial antibodies: controversial results on porcine sperm CD44 receptor identification2019Ingår i: Reproduction in domestic animals, ISSN 0936-6768, E-ISSN 1439-0531, Vol. 54, nr 4, s. 733-737Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Presence of the hyaluronan (hyaluronic acid, HA) receptor CD44 on spermatozoa has been difficult to pursue, mostly obeying to the use of different commercial mono- and/or polyclonal antibodies, often lacking proper controls. Here, we describe how the presence (Western blotting) and specific location (immunocytochemistry) of the CD44 receptor differs in ejaculated pig spermatozoa depending on the type of antibody and protocol used. While we were able to detect binding to spermatozoa and mark its presence in the sperm membrane, the use of blocking peptides clearly indicated that only the monoclonal antibody could confirm the specific presence and location of the CD44 receptor, whereas the polyclonal antibody was detecting multiple presumed CD44 isoforms or degraded proteins thus proving unspecific. These results call for strict protocols when attempting immunological determination of sperm membrane receptors.

    Publikationen är tillgänglig i fulltext från 2020-02-11 15:44
  • 224.
    Alvarez-Rodriguez, Manuel
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten.
    Vicente Carrillo, Alejandro
    Linköpings universitet, Medicinska fakulteten. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för barns och kvinnors hälsa. Evidensia Valla Djursjukhus Linkoping, Linkoping, Sweden.
    Rodriguez-Martinez, Heriberto
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten.
    Hyaluronan improves neither the long-term storage nor the cryosurvival of liquid-stored CD44-bearing Al boar spermatozoa2018Ingår i: Journal of reproduction and development, ISSN 0916-8818, E-ISSN 1348-4400, Vol. 64, nr 4, s. 351-360Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Hyaluronan (hyaluronic acid, HA) apparently improves sperm survival in vitro and in vivo (oviduct), maintaining sperm motility and inducing capacitation, but not acrosome exocytosis, either by direct action as a macromolecule or via CD44 membrane receptors. This study explored ejaculated, liquid-extended pig spermatozoa to ascertain (i) the presence (Western blotting) and specific location (immunocytochemistry) of the CD44 receptor, using a specific monoclonal commercial antibody; (ii) whether the CD44 receptor changed location when exposed to bicarbonate, a capacitating trigger, in vitro; and (iii) whether the addition of HA, of molecular size comparable to that produced in the oviduct sperm reservoir (0.0625 to 2.0 mg/ml; 0 HA: control), to semen extenders would improve sperm liquid storage in vitro or cryosurvival post freezing. Variables tested were sperm velocity and progressive motility (Qualisperm (TM)), sperm viability and acrosome status, membrane integrity and early destabilization, mitochondrial activation, and superoxide production (flow cytometry). The CD44 receptor presence in ejaculated, liquid-stored AI boar spermatozoa, as confirmed by a porcine-specific monoclonal antibody, maintained its membrane location under in vitro capacitation-inducing conditions. HA exposure to 24-, 48-, or 72-h liquid-stored (17-20 degrees C) spermatozoa lowered sperm velocity in membrane-intact spermatozoa, but increased mitochondrial superoxide production. Finally, HA addition during cooling did not improve cryosurvival but did increase mitochondrial activation and membrane destabilization in surviving cells. These results confirm the existence of a CD44 receptor in pig spermatozoa, but the usefulness of adding HA for long-term storage or cryopreservation of liquid-stored, extended boar semen remains in question, thereby warranting further non-empirical analyses of HA-sperm membrane interactions.

  • 225.
    Alvarez-Rodriguez, Manuel
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten.
    Vicente-Carrillo, Alejandro
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten.
    Rodriguez-Martinez, Heriberto
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten.
    Exogenous Individual Lecithin-Phospholipids (Phosphatidylcholine and Phosphatidylglycerol) Cannot Prevent the Oxidative Stress Imposed by Cryopreservation of Boar Sperm.2017Ingår i: Journal of veterinary medicine and surgery, ISSN 2574-2868, Vol. 1, nr 1Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: Despite the use of high proportions of the chemically undefined lipoprotein/phospholipid-rich egg-yolk in extenders, boar sperm are highly sensitive to cooling, which induces ROS generation and disrupts the plasma membrane.

    Here, we studied whether replacement of hen egg-yolk by commercially defined lecithin phospholipids, derived from egg (LPGE: phosphatidyl glycerol, LPCE: phosphatidyl choline) or soybean (LPCS: phosphatidyl choline), could individually ameliorate such oxidative effects during cryopreservation of ejaculated (sperm rich fraction, SRF) or of cauda-epididymal sperm, retrieved post-mortem from the same males.

    Methods: A conventional extender (lactose buffer, with 20% egg-yolk, 0.5% OEP and 3% glycerol) was used as control. Cryodamage was assessed as loss of sperm motility, membrane and acrosome intactness, early membrane destabilization changes, mitochondrial potential, superoxide and ROS production, to finally determine lipid peroxidation (LPO) using specific probes.

    Results and conclusion: In general, the exogenous phospholipids assayed were unable of maintaining neither sperm motility nor viability post-thaw compared to controls, owing to increased ROS production and lipid peroxidation. In our study, mitochondrial superoxide production resulted in very high levels for all groups, whereas both ROS production and lipid peroxidation were reduced in the control group, containing emulsified hen egg yolk. Further studies using various dosage and combination of LPCS should be followed for their eventual protective effect.

    Keywords: Cryodamage; Sperm; Boar; Mitochondrial activation; Mitochondrial superoxide; ROS production; Lipid peroxidation

  • 226.
    Alvarsson, Michael
    et al.
    Institutionen för molekylär medicin och kirurgi, Karolinska institutet - PO Endokrinologi och njurmedicin Stockholm, Sweden Institutionen för molekylär medicin och kirurgi, Karolinska institutet - PO Endokrinologi och njurmedicin Stockholm, Sweden.
    Östgren, Carl Johan
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för samhällsmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Primärvårdscentrum, Vårdcentralen Ödeshög.
    Ny era inom terapin för typ 2-diabetes – men vad är nytt?: Metformin fortfarande förstahandsval, men därefter rekommenderas att behandlingen individualiseras2018Ingår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 115Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    n/a

  • 227.
    Alwin, Jenny
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för hälso- och sjukvårdsanalys. Linköpings universitet, Medicinska fakulteten.
    Lundqvist, Martina
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för hälso- och sjukvårdsanalys. Linköpings universitet, Hälsouniversitetet.
    Lundqvist, Martina
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för hälso- och sjukvårdsanalys. Linköpings universitet, Medicinska fakulteten.
    Husberg, Magnus
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för hälso- och sjukvårdsanalys. Linköpings universitet, Hälsouniversitetet.
    Levin, Lars-Åke
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för hälso- och sjukvårdsanalys. Linköpings universitet, Hälsouniversitetet.
    Utvärdering av försöksverksamhet med service- och signalhundar2014Rapport (Övrigt vetenskapligt)
    Abstract [sv]

    Denna rapport redovisar utvärderingen av en försöksverksamhet med ser-vice- och signalhundar som bedrevs mellan år 2009 och 2014. Utvärderingen inkluderar servicehundar, signalhundar samt alarmerande servicehundar (epilepsihundar och diabeteshundar). Totalt 56 ekipage (förare samt hund) ingick i utvärderingsstudien. Data i studien samlades in före samt efter genomgången service- och signalhundsutbildning. Syftet med utvärderingen är att studera hur certifierade service- och signalhundar påverkar förarnas behov av offentliga stödinsatser och de totala samhällskostnaderna. Dessutom studerades hur service- och signalhundar påverkar förarna med avseende på hälsorelaterad livskvalitet, välbefinnande, självförtroende och fysisk aktivitet samt om användningen av service- och signalhundar är kostnadseffektiv ur ett samhällsperspektiv.

      Resultat och slutsatser

    • Service- och signalhundar minskar i genomsnitt förarnas behov av offentliga stödinsatser med 197 000 kronor (6 procent) under en tioårsperiod.
    • Livskvaliteten för personer med behov av service- och signalhundar är låg jämfört med den allmänna populationen i Sverige. Studien visar på en förbättring i livskvaliteten och välbefinnandet för förare med en certifierad hund.
    • Förarnas grad av fysisk aktivitet ökade med en certifierad hund och majoriteten av dem angav att de ökat sin tid utanför hemmet samt att de även ökat sin tid för att delta i sociala aktiviteter tack vare hunden.
    • Förarnas negativa emotionella upplevelser minskar med en certifierad hund.
    • Förarna beskriver själva den certifierade hunden som ett viktigt verktyg för ökad självständighet och trygghet.
    • Den hälsoekonomiska modellen som analyserar kostnadseffektiviteten visar att ett innehav av en certifierad hund är ett dominant alternativ jämfört med att inte ha en certifierad hund. Detta innebär att kostnaderna ur ett samhällsperspektiv under en tioårsperiod är lägre (-103 000 kronor) samtidigt som effekterna i form av vunna QALY (kvalitetsjusterade levnadsår) är högre (+0,15).
    • Finansieringsanalysen visar att förare som har certifierade hundar sparar resurser åt alla aktörer (stat, kommun och landsting) men får själva ökade utgifter på grund av hunden.
    • Studien baseras på ett lågt antal observationer (56 ekipage). Det i kombination med att det är en stor spridning i resursförbrukningen mellan ekipagen medför att det finns en statistisk osäkerhet i resultaten. Slutsatserna bedöms dock som rimliga eftersom de är samstämmiga.
  • 228.
    Aman, Malin
    et al.
    Swedish Sch Sport and Hlth Sci, Sweden.
    Larsen, Karin
    Swedish Sch Sport and Hlth Sci, Sweden; Umea Univ, Sweden.
    Forssblad, Magnus
    Swedish Sch Sport and Hlth Sci, Sweden; Karolinska Inst, Sweden.
    Näsmark, Annica
    Swedish Sch Sport and Hlth Sci, Sweden; Capio Artro Clin, Sweden.
    Waldén, Markus
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för samhällsmedicin. Linköpings universitet, Medicinska fakulteten. Swedish Sch Sport and Hlth Sci, Sweden.
    Hägglund, Martin
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för fysioterapi. Linköpings universitet, Medicinska fakulteten. Swedish Sch Sport and Hlth Sci, Sweden.
    A Nationwide Follow-up Survey on the Effectiveness of an Implemented Neuromuscular Training Program to Reduce Acute Knee Injuries in Soccer Players2018Ingår i: The Orthopaedic Journal of Sports Medicine, ISSN 2325-9671, Vol. 6, nr 12, artikel-id 2325967118813841Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: A cruciate ligament (CL) injury is a severe injury in soccer. Neuromuscular training programs have a well-documented preventive effect, but there are few studies on the effectiveness of such a program at a national level. The Swedish Knee Control Program (KCP) was found to be effective in preventing CL injuries in youth female soccer players. The KCP was implemented nationwide in Sweden in 2010. Purpose: To evaluate the effectiveness of the Swedish KCP in reducing acute knee injuries in soccer players at a nationwide level. Study Design: Descriptive epidemiology study. Methods: All licensed soccer players in Sweden are covered by the same insurance company. Using this insurance database, around 17,500 acute knee injuries that were reported to the insurance company between 2006 and 2015 were included in the study. By matching the number of licensed soccer players with the number of reported injuries each year, the annual incidence of knee and CL injuries was able to be calculated. To evaluate the spread of the KCP nationally, a questionnaire was sent to all 24 Swedish district football associations (FAs) with questions regarding KCP education. The number of downloads of the KCP mobile application (app) was obtained. Results: The incidence of CL injuries decreased during the study period for both male (from 2.9 to 2.4 per 1000 player-years) and female players (from 4.9 to 3.9 per 1000 player-years). The overall incidence of knee injuries decreased in both male (from 5.6 to 4.6 per 1000 player-years) and female players (from 8.7 to 6.4 per 1000 player-years). Comparing before and after the nationwide implementation of the KCP, there was a decrease in the incidence of CL injuries by 6% (rate ratio [RR], 0.94 [95% CI, 0.89-0.98]) in male players and 13% (RR, 0.87 [95% CI, 0.81-0.92]) in female players and a decrease in the incidence of knee injuries by 8% (RR, 0.92 [95% CI, 0.89-0.96]) and 21% (RR, 0.79 [95% CI, 0.75-0.83]), respectively (P amp;lt; .01 for all). This trend corresponded to a reduction of approximately 100 CL injuries each year in Sweden. A total of 21 of 24 district FAs held organized KCP educational courses during the study period. The percentage of district FAs holding KCP courses was between 46% and 79% each year. There were 101,236 downloads of the KCP app. Conclusion: The KCP can be considered partially implemented nationwide, and the incidence of knee and CL injuries has decreased in both sexes at a nationwide level.

  • 229.
    Amirhosseini, Mehdi
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Aseptic Loosening of Orthopedic Implants: Osteoclastogenesis Regulation and Potential Therapeutics2019Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Aseptic loosening is the main cause of failure of orthopedic prostheses. With no pharmaceuticals to prevent or mitigate periprosthetic bone degradation, a surgery to replace the loose implant with a new one is the only choice to restore patients’ function. Most studies on mechanisms for aseptic loosening investigate wear debris particle-induced osteolysis. However, pathological loading conditions around unstable implants can also trigger osteoclast differentiation and bone loss.

    In the first study, global gene expression changes induced by mechanical instability of implants, and by titanium particles were compared in a validated rat model for aseptic loosening. Microarray analysis showed that similar signaling pathways and gene expression patterns are involved in particle- and instability-induced periprosthetic osteolysis with an early onset innate immune response as a hallmark of osteolysis induced by mechanical instability.

    Further, effects of potential therapeutics on restriction of excessive osteoclast differentiation were evaluated. Wnt signaling pathway is known to regulate bone remodeling. In the second study, effects of inactivation of glycogen synthase kinase 3 beta (GSK-3β), a negative regulator of canonical Wnt signaling, on instability-induced periprosthetic osteolysis were examined using our rat model for aseptic loosening. Inhibition of GSK-3β led to a decrease in osteoclast numbers in the periprosthetic bone tissue exposed to mechanical instability while osteoblast perimeter showed an increase. This was accompanied by higher bone volume fraction (BV/TV) in animals treated with the GSK-3β inhibitor.

    In the third study, potential beneficial effects of two selective inhibitors of cyclindependent kinase 8/19 (CDK8/19) on bone tissue were evaluated. CDK8/19 is a Mediator complex-associated transcriptional regulator involved in several signaling pathways. CDK8/19 inhibitors, mainly under investigation as treatments for tumors, are reported to enhance osteoblast differentiation and bone formation. We show in this study, for the first time, that inhibition of CDK8/19 led to marked suppression of osteoclast differentiation from bone marrow macrophages in vitro through disruption of the RANK signaling. In mouse primary osteoblasts downregulation of osteopontin mRNA, a negative regulator of mineralization, together with increased alkaline phosphatase activity and calcium deposition indicated that osteoblast mineralization was promoted by CDK8/19 inhibition. Moreover, local administration of a CDK8/19 inhibitor promoted cancellous bone regeneration in a rat model for bone healing.

    These studies contribute to better understanding of mechanisms behind mechanical instability-induced periprosthetic osteolysis and propose potential therapeutics to restrict bone loss with effects on both osteoclasts and osteoblasts.

    Delarbeten
    1. Mechanical instability and titanium particles induce similar transcriptomic changes in a rat model for periprosthetic osteolysis and aseptic loosening
    Öppna denna publikation i ny flik eller fönster >>Mechanical instability and titanium particles induce similar transcriptomic changes in a rat model for periprosthetic osteolysis and aseptic loosening
    2017 (Engelska)Ingår i: Bone Reports, ISSN 2352-1872, Vol. 7, s. 17-25Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Wear debris particles released from prosthetic bearing surfaces and mechanical instability of implants are two main causes of periprosthetic osteolysis. While particle-induced loosening has been studied extensively, mechanisms through which mechanical factors lead to implant loosening have been less investigated. This study compares the transcriptional profiles associated with osteolysis in a rat model for aseptic loosening, induced by either mechanical instability or titanium particles. Rats were exposed to mechanical instability or titanium particles. After 15 min, 3, 48 or 120 h from start of the stimulation, gene expression changes in periprosthetic bone tissue was determined by microarray analysis. Microarray data were analyzed by PANTHER Gene List Analysis tool and Ingenuity Pathway Analysis (IPA). Both types of osteolytic stimulation led to gene regulation in comparison to unstimulated controls after 3, 48 or 120 h. However, when mechanical instability was compared to titanium particles, no gene showed a statistically significant difference (fold change = ± 1.5 and adjusted p-value = 0.05) at any time point. There was a remarkable similarity in numbers and functional classification of regulated genes. Pathway analysis showed several inflammatory pathways activated by both stimuli, including Acute Phase Response signaling, IL-6 signaling and Oncostatin M signaling. Quantitative PCR confirmed the changes in expression of key genes involved in osteolysis observed by global transcriptomics. Inflammatory mediators including interleukin (IL)-6, IL-1ß, chemokine (C-C motif) ligand (CCL)2, prostaglandin-endoperoxide synthase (Ptgs)2 and leukemia inhibitory factor (LIF) showed strong upregulation, as assessed by both microarray and qPCR. By investigating genome-wide expression changes we show that, despite the different nature of mechanical implant instability and titanium particles, osteolysis seems to be induced through similar biological and signaling pathways in this rat model for aseptic loosening. Pathways associated to the innate inflammatory response appear to be a major driver for osteolysis. Our findings implicate early restriction of inflammation to be critical to prevent or mitigate osteolysis and aseptic loosening of orthopedic implants.

    Ort, förlag, år, upplaga, sidor
    Elsevier, 2017
    Nyckelord
    Aseptic loosening; Implant; Instability; Microarray; Wear debris
    Nationell ämneskategori
    Cell- och molekylärbiologi Ortopedi
    Identifikatorer
    urn:nbn:se:liu:diva-146297 (URN)10.1016/j.bonr.2017.07.003 (DOI)28795083 (PubMedID)
    Tillgänglig från: 2018-04-07 Skapad: 2018-04-07 Senast uppdaterad: 2019-03-08
    2. GSK-3 beta inhibition suppresses instability-induced osteolysis by a dual action on osteoblast and osteoclast differentiation
    Öppna denna publikation i ny flik eller fönster >>GSK-3 beta inhibition suppresses instability-induced osteolysis by a dual action on osteoblast and osteoclast differentiation
    Visa övriga...
    2018 (Engelska)Ingår i: Journal of Cellular Physiology, ISSN 0021-9541, E-ISSN 1097-4652, Vol. 233, nr 3, s. 2398-2408Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Currently, there are no medications available to treat aseptic loosening of orthopedic implants. Using osteoprotegerin fusion protein (OPG-Fc), we previously blocked instability-induced osteoclast differentiation and peri-prosthetic osteolysis. Wnt/beta-catenin signaling, which regulates OPG secretion from osteoblasts, also modulates the bone tissue response to mechanical loading. We hypothesized that activating Wnt/beta-catenin signaling by inhibiting glycogen synthase kinase-3 beta (GSK-3 beta) would reduce instability-induced bone loss through regulation of both osteoblast and osteoclast differentiation. We examined effects of GSK-3 beta inhibition on regulation of RANKL and OPG in a rat model of mechanical instability-induced peri-implant osteolysis. The rats were treated daily with a GSK-3 beta inhibitor, AR28 (20 mg/kg bw), for up to 5 days. Bone tissue and blood serum were assessed by qRT-PCR, immunohistochemistry, and ELISA on days 3 and 5, and by micro-CT on day 5. After 3 days of treatment with AR28, mRNA levels of beta-catenin, Runx2, Osterix, Col1 alpha 1, and ALP were increased leading to higher osteoblast numbers compared to vehicle-treated animals. BMP-2 and Wnt16 mRNA levels were downregulated by mechanical instability and this was rescued by GSK-3 beta inhibition. Osteoclast numbers were decreased significantly after 3 days of GSK-3 beta inhibition, which correlated with enhanced OPG mRNA expression. This was accompanied by decreased serum levels of TRAP5b on days 3 and 5. Treatment with AR28 upregulated osteoblast differentiation, while osteoclastogenesis was blunted, leading to increased bone mass by day 5. These data suggest that GSK-3 beta inactivation suppresses osteolysis through regulating both osteoblast and osteoclast differentiation in a rat model of instability-induced osteolysis.

    Ort, förlag, år, upplaga, sidor
    WILEY, 2018
    Nyckelord
    bone implant; GSK-3 beta; mechanical instability; osteolysis; Wnt signaling
    Nationell ämneskategori
    Farmakologi och toxikologi
    Identifikatorer
    urn:nbn:se:liu:diva-148660 (URN)10.1002/jcp.26111 (DOI)000433519300056 ()28731198 (PubMedID)
    Anmärkning

    Funding Agencies|VINNOVA [2012-04409]; National Institutes of Health [AR056802]; Vetenskapsradet [K2014-7X-22506-01-3]; Swedish Research Council; Swedish Governmental Agency for Innovation Systems

    Tillgänglig från: 2018-06-18 Skapad: 2018-06-18 Senast uppdaterad: 2019-04-08
    3. Cyclin-dependent kinase 8/19 inhibition suppresses osteoclastogenesis by downregulating RANK and promotes osteoblast mineralization and cancellous bone healing.
    Öppna denna publikation i ny flik eller fönster >>Cyclin-dependent kinase 8/19 inhibition suppresses osteoclastogenesis by downregulating RANK and promotes osteoblast mineralization and cancellous bone healing.
    Visa övriga...
    2019 (Engelska)Ingår i: Journal of Cellular Physiology, ISSN 0021-9541, E-ISSN 1097-4652, Vol. 234, nr 9, s. 16503-16516Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Cyclin-dependent kinase 8 (CDK8) is a mediator complex-associated transcriptional regulator that acts depending on context and cell type. While primarily under investigation as potential cancer therapeutics, some inhibitors of CDK8-and its paralog CDK19-have been reported to affect the osteoblast lineage and bone formation. This study investigated the effects of two selective CDK8/19 inhibitors on osteoclastogenesis and osteoblasts in vitro, and further evaluated how local treatment with a CDK8/19 inhibitor affects cancellous bone healing in rats. CDK8/19 inhibitors did not alter the proliferation of neither mouse bone marrow-derived macrophages (BMMs) nor primary mouse osteoblasts. Receptor activator of nuclear factor κΒ (NF-κB) ligand (RANKL)-induced osteoclastogenesis from mouse BMMs was suppressed markedly by inhibition of CDK8/19, concomitant with reduced tartrate-resistant acid phosphatase (TRAP) activity and C-terminal telopeptide of type I collagen levels. This was accompanied by downregulation of PU.1, RANK, NF-κB, nuclear factor of activated T-cells 1 (NFATc1), dendritic cell-specific transmembrane protein (DC-STAMP), TRAP, and cathepsin K in RANKL-stimulated BMMs. Downregulating RANK and its downstream signaling in osteoclast precursors enforce CDK8/19 inhibitors as anticatabolic agents to impede excessive osteoclastogenesis. In mouse primary osteoblasts, CDK8/19 inhibition did not affect differentiation but enhanced osteoblast mineralization by promoting alkaline phosphatase activity and downregulating osteopontin, a negative regulator of mineralization. In rat tibiae, a CDK8/19 inhibitor administered locally promoted cancellous bone regeneration. Our data indicate that inhibitors of CDK8/19 have the potential to develop into therapeutics to restrict osteolysis and enhance bone regeneration.

    Nyckelord
    CDK8, RANK, osteoblasts, osteoclasts
    Nationell ämneskategori
    Cell- och molekylärbiologi Läkemedelskemi
    Identifikatorer
    urn:nbn:se:liu:diva-154927 (URN)10.1002/jcp.28321 (DOI)000470174200186 ()30793301 (PubMedID)
    Anmärkning

    Funding agencies: Vetenskapsradet [521-2013-2593, 2016-06097, K2015-99x-10363-23-4, 2016-01822]; Swedish Research Council

    Tillgänglig från: 2019-03-05 Skapad: 2019-03-05 Senast uppdaterad: 2019-07-03
  • 230.
    Amirhosseini, Mehdi
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Andersson, Göran
    Division of Pathology, Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital, Huddinge, Sweden.
    Aspenberg, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Ortopedkliniken i Linköping.
    Fahlgren, Anna
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Mechanical instability and titanium particles induce similar transcriptomic changes in a rat model for periprosthetic osteolysis and aseptic loosening2017Ingår i: Bone Reports, ISSN 2352-1872, Vol. 7, s. 17-25Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Wear debris particles released from prosthetic bearing surfaces and mechanical instability of implants are two main causes of periprosthetic osteolysis. While particle-induced loosening has been studied extensively, mechanisms through which mechanical factors lead to implant loosening have been less investigated. This study compares the transcriptional profiles associated with osteolysis in a rat model for aseptic loosening, induced by either mechanical instability or titanium particles. Rats were exposed to mechanical instability or titanium particles. After 15 min, 3, 48 or 120 h from start of the stimulation, gene expression changes in periprosthetic bone tissue was determined by microarray analysis. Microarray data were analyzed by PANTHER Gene List Analysis tool and Ingenuity Pathway Analysis (IPA). Both types of osteolytic stimulation led to gene regulation in comparison to unstimulated controls after 3, 48 or 120 h. However, when mechanical instability was compared to titanium particles, no gene showed a statistically significant difference (fold change = ± 1.5 and adjusted p-value = 0.05) at any time point. There was a remarkable similarity in numbers and functional classification of regulated genes. Pathway analysis showed several inflammatory pathways activated by both stimuli, including Acute Phase Response signaling, IL-6 signaling and Oncostatin M signaling. Quantitative PCR confirmed the changes in expression of key genes involved in osteolysis observed by global transcriptomics. Inflammatory mediators including interleukin (IL)-6, IL-1ß, chemokine (C-C motif) ligand (CCL)2, prostaglandin-endoperoxide synthase (Ptgs)2 and leukemia inhibitory factor (LIF) showed strong upregulation, as assessed by both microarray and qPCR. By investigating genome-wide expression changes we show that, despite the different nature of mechanical implant instability and titanium particles, osteolysis seems to be induced through similar biological and signaling pathways in this rat model for aseptic loosening. Pathways associated to the innate inflammatory response appear to be a major driver for osteolysis. Our findings implicate early restriction of inflammation to be critical to prevent or mitigate osteolysis and aseptic loosening of orthopedic implants.

  • 231.
    Amirhosseini, Mehdi
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Bernhardsson, Magnus
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten.
    Lång, Pernilla
    Department of Laboratory Medicine, Division of Pathology, Karolinska Institutet, Karolinska University Hospital, Huddinge, Sweden.
    Andersson, Göran
    Department of Laboratory Medicine, Division of Pathology, Karolinska Institutet, Karolinska University Hospital, Huddinge, Sweden.
    Flygare, Johan
    Department of Molecular Medicine and Gene Therapy, Lund Stem Cell Center, Lund University, Lund, Sweden..
    Fahlgren, Anna
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Cyclin-dependent kinase 8/19 inhibition suppresses osteoclastogenesis by downregulating RANK and promotes osteoblast mineralization and cancellous bone healing.2019Ingår i: Journal of Cellular Physiology, ISSN 0021-9541, E-ISSN 1097-4652, Vol. 234, nr 9, s. 16503-16516Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Cyclin-dependent kinase 8 (CDK8) is a mediator complex-associated transcriptional regulator that acts depending on context and cell type. While primarily under investigation as potential cancer therapeutics, some inhibitors of CDK8-and its paralog CDK19-have been reported to affect the osteoblast lineage and bone formation. This study investigated the effects of two selective CDK8/19 inhibitors on osteoclastogenesis and osteoblasts in vitro, and further evaluated how local treatment with a CDK8/19 inhibitor affects cancellous bone healing in rats. CDK8/19 inhibitors did not alter the proliferation of neither mouse bone marrow-derived macrophages (BMMs) nor primary mouse osteoblasts. Receptor activator of nuclear factor κΒ (NF-κB) ligand (RANKL)-induced osteoclastogenesis from mouse BMMs was suppressed markedly by inhibition of CDK8/19, concomitant with reduced tartrate-resistant acid phosphatase (TRAP) activity and C-terminal telopeptide of type I collagen levels. This was accompanied by downregulation of PU.1, RANK, NF-κB, nuclear factor of activated T-cells 1 (NFATc1), dendritic cell-specific transmembrane protein (DC-STAMP), TRAP, and cathepsin K in RANKL-stimulated BMMs. Downregulating RANK and its downstream signaling in osteoclast precursors enforce CDK8/19 inhibitors as anticatabolic agents to impede excessive osteoclastogenesis. In mouse primary osteoblasts, CDK8/19 inhibition did not affect differentiation but enhanced osteoblast mineralization by promoting alkaline phosphatase activity and downregulating osteopontin, a negative regulator of mineralization. In rat tibiae, a CDK8/19 inhibitor administered locally promoted cancellous bone regeneration. Our data indicate that inhibitors of CDK8/19 have the potential to develop into therapeutics to restrict osteolysis and enhance bone regeneration.

    Publikationen är tillgänglig i fulltext från 2020-02-21 12:44
  • 232.
    Amirhosseini, Mehdi
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Madsen, Rune V.
    Hosp Special Surg, NY 10021 USA.
    Escott, K. Jane
    AstraZeneca, England.
    Bostrom, Mathias P.
    Hosp Special Surg, NY 10021 USA.
    Ross, F. Patrick
    Hosp Special Surg, NY 10021 USA.
    Fahlgren, Anna
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    GSK-3 beta inhibition suppresses instability-induced osteolysis by a dual action on osteoblast and osteoclast differentiation2018Ingår i: Journal of Cellular Physiology, ISSN 0021-9541, E-ISSN 1097-4652, Vol. 233, nr 3, s. 2398-2408Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Currently, there are no medications available to treat aseptic loosening of orthopedic implants. Using osteoprotegerin fusion protein (OPG-Fc), we previously blocked instability-induced osteoclast differentiation and peri-prosthetic osteolysis. Wnt/beta-catenin signaling, which regulates OPG secretion from osteoblasts, also modulates the bone tissue response to mechanical loading. We hypothesized that activating Wnt/beta-catenin signaling by inhibiting glycogen synthase kinase-3 beta (GSK-3 beta) would reduce instability-induced bone loss through regulation of both osteoblast and osteoclast differentiation. We examined effects of GSK-3 beta inhibition on regulation of RANKL and OPG in a rat model of mechanical instability-induced peri-implant osteolysis. The rats were treated daily with a GSK-3 beta inhibitor, AR28 (20 mg/kg bw), for up to 5 days. Bone tissue and blood serum were assessed by qRT-PCR, immunohistochemistry, and ELISA on days 3 and 5, and by micro-CT on day 5. After 3 days of treatment with AR28, mRNA levels of beta-catenin, Runx2, Osterix, Col1 alpha 1, and ALP were increased leading to higher osteoblast numbers compared to vehicle-treated animals. BMP-2 and Wnt16 mRNA levels were downregulated by mechanical instability and this was rescued by GSK-3 beta inhibition. Osteoclast numbers were decreased significantly after 3 days of GSK-3 beta inhibition, which correlated with enhanced OPG mRNA expression. This was accompanied by decreased serum levels of TRAP5b on days 3 and 5. Treatment with AR28 upregulated osteoblast differentiation, while osteoclastogenesis was blunted, leading to increased bone mass by day 5. These data suggest that GSK-3 beta inactivation suppresses osteolysis through regulating both osteoblast and osteoclast differentiation in a rat model of instability-induced osteolysis.

  • 233.
    Amiri Arimi, Somayeh
    et al.
    Shahid Beheshti University of Medical Sciences, Physiotherapy Research Center, School of Rehabilitation, Department of Physiotherapy, Tehran, Iran; University of Social Welfare and Rehabilitation Sciences, Department of Physiotherapy, Tehran, Iran.
    Mohseni Bandpei, Mohammad Ali
    Pediatric Neurorehabilitation Research Center, Department of Physiotherapy, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran; University Institute of Physical Therapy, Faculty of Allied Health Sciences, University of Lahore, Lahore, Pakistan.
    Rezasoltani, Asghar
    Shahid Beheshti University of Medical Sciences, Physiotherapy Research Centre, School of Rehabilitation, Tehran, Iran.
    Peolsson, Anneli
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för fysioterapi. Linköpings universitet, Medicinska fakulteten.
    Mohammadi, Masumeh
    Shahid Beheshti University of Medical Sciences, Physiotherapy Research Center, School of Rehabilitation, Department of Physiotherapy, Tehran, Iran.
    Multifidus muscle size changes at different directions of head and neck movements in females with unilateral chronic non-specific neck pain and healthy subjects using ultrasonography2018Ingår i: Journal of Bodywork & Movement Therapies, ISSN 1360-8592, E-ISSN 1532-9283, Vol. 22, nr 3, s. 560-565Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: The aim of the study was to compare the dimensions of cervical multifidus muscle (CMM) in different conditions.

    METHODS: Twenty five women with neck pain and 25 healthy subjects participated in this study. The dimensions of the CMM were measured at rest, 50% and 100% maximum isometric voluntary contraction (MIVC) at six directions of neck movements, using ultrasonography.

    RESULTS: The size of multifidus was smaller in patients than healthy individuals at rest state (P < 0.05). A significant smaller CMM dimension was found in the affected side compared with unaffected side in patients group (P < 0.05). The result of ANOVA for MLD showed a significant difference for contraction levels (P < 0.001) and neck movements (P < 0.001) in both groups. The MLD of the CMM was significantly different between CMM at rest and 50%, and 100% MIVC (P < 0.001). No significant differences were found between the groups at 50% and 100% MIVC (P > 0.05 in both instances). The most prominent CMM size change was observed during neck extension, flexion, ipsilateral lateral-flexion, and ipsilateral rotation, respectively (P < 0.05).

    CONCLUSIONS: Results of the present study indicate that the size of CMM was decreased in patients with neck pain in rest state. The size of CMM changes in all directions of neck movements, although the most prominent was during neck extension. This points out CMM stabilization role's in different directions of neck movements.

  • 234.
    Amundstuen Reppe, Linda
    et al.
    Nordic University, Norway; Norwegian University of Science and Technology, Norway; St Olays Hospital, Norway.
    Lydersen, Stian
    Norwegian University of Science and Technology, Norway.
    Schjott, Jan
    Haukeland Hospital, Norway; University of Bergen, Norway; Haukeland Hospital, Norway.
    Damkier, Per
    Odense University Hospital, Denmark.
    Rolighed Christensen, Hanne
    Bispebjerg and Frederiksberg University Hospital, Denmark.
    Peter Kampmann, Jens
    Bispebjerg and Frederiksberg University Hospital, Denmark.
    Böttiger, Ylva
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för läkemedelsforskning. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk farmakologi.
    Spigset, Olav
    Norwegian University of Science and Technology, Norway; St Olays Hospital, Norway.
    Relationship Between Time Consumption and Quality of Responses to Drug-related Queries: A Study From Seven Drug Information Centers in Scandinavia2016Ingår i: Clinical Therapeutics, ISSN 0149-2918, E-ISSN 1879-114X, Vol. 38, nr 7, s. 1738-1749Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose: The aims of this study were to assess the quality of responses produced by drug information centers (DICs) in Scandinavia, and to study the association between time consumption processing queries and the quality of the responses. Methods: We posed six identical drug-related queries to seven DICs in Scandinavia, and the time consumption required for processing them was estimated. Clinical pharmacologists (internal experts) and general practitioners (external experts) reviewed responses individually. We used mixed model linear regression analyses to study the associations between time consumption on one hand and the summarized quality scores and the overall impression of the responses on the other hand. Findings: Both expert groups generally assessed the quality of the responses as "satisfactory" to "good." A few responses were criticized for being poorly synthesized and less relevant, of which none were quality-assured using co-signatures. For external experts, an increase in time consumption was statistically significantly associated with a decrease in common quality score (change in score, -0.20 per hour of work; 95% CI, -0.33 to -0.06; P = 0.004), and overall impression (change in score, -0.05 per hour of work; 95% CI, -0.08 to -0.01; P = 0.005). No such associations were found for the internal experts assessment. Implications: To our knowledge, this is the first study of the association between time consumption and quality of responses to drug-related queries in DICs. The quality of responses were in general good, but time consumption and quality were only weakly associated in this setting. (C) 2016 The Authors. Published by Elsevier HS Journals, Inc.

  • 235.
    Amundstuen Reppe, Linda
    et al.
    Nordic University, Norway; Norwegian University of Science and Technology, Norway; St Olavs Hospital, Norway.
    Spigset, Olav
    Norwegian University of Science and Technology, Norway; St Olavs Hospital, Norway.
    Kampmann, Jens Peter
    Bispebjerg Hospital, Denmark.
    Damkier, Per
    Odense University Hospital, Denmark.
    Rolighed Christensen, Hanne
    Bispebjerg Hospital, Denmark.
    Böttiger, Ylva
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för läkemedelsforskning. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk farmakologi.
    Schjott, Jan
    Haukeland Hospital, Norway; University of Bergen, Norway; Haukeland Hospital, Norway.
    Quality assessment of structure and language elements of written responses given by seven Scandinavian drug information centres2017Ingår i: European Journal of Clinical Pharmacology, ISSN 0031-6970, E-ISSN 1432-1041, Vol. 73, nr 5, s. 623-631Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The aim of this study was to identify structure and language elements affecting the quality of responses from Scandinavian drug information centres (DICs). Six different fictitious drug-related queries were sent to each of seven Scandinavian DICs. The centres were blinded for which queries were part of the study. The responses were assessed qualitatively by six clinical pharmacologists (internal experts) and six general practitioners (GPs, external experts). In addition, linguistic aspects of the responses were evaluated by a plain language expert. The quality of responses was generally judged as satisfactory to good. Presenting specific advice and conclusions were considered to improve the quality of the responses. However, small nuances in language formulations could affect the individual judgments of the experts, e.g. on whether or not advice was given. Some experts preferred the use of primary sources to the use of secondary and tertiary sources. Both internal and external experts criticised the use of abbreviations, professional terminology and study findings that was left unexplained. The plain language expert emphasised the importance of defining and explaining pharmacological terms to ensure that enquirers understand the response as intended. In addition, more use of active voice and less compressed text structure would be desirable. This evaluation of responses to DIC queries may give some indications on how to improve written responses on drug-related queries with respect to language and text structure. Giving specific advice and precise conclusions and avoiding too compressed language and non-standard abbreviations may aid to reach this goal.

  • 236.
    Anagnostopoulos, Dimitris C.
    et al.
    University of Athens, Greece.
    Heberbrand, Johannes
    University of Duisburg Essen, Germany.
    Eliez, Stephan
    University of Geneva, Switzerland.
    Doyle, Maeve B.
    St Davnets Hospital, Ireland.
    Klasen, Henrikje
    Leiden University, Netherlands.
    Crommen, Sofie
    Flemish Assoc Child and Adolescent Psychiat, Belgium.
    Cetin Cuhadaroglu, Fusun
    Hacettepe University, Turkey.
    Pejovic-Milovancevic, Milica
    University of Belgrade, Serbia.
    Herreros, Oscar
    Hospital University of Virgen de las Nieves, Spain.
    Minderaa, Ruud
    European Soc Child and Adolescent Psychiat, Belgium.
    Karwautz, Andreas
    Medical University of Vienna, Austria.
    Svedin, Carl Göran
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Närsjukvården i centrala Östergötland, Barn- och ungdomspsykiatriska kliniken.
    Raynaud, Jean Philippe
    Centre Hospital University of Toulouse, France.
    Editorial Material: European Society of Child and Adolescent Psychiatry: position statement on mental health of child and adolescent refugees in EUROPEAN CHILD and ADOLESCENT PSYCHIATRY, vol 25, issue 7, pp 673-6762016Ingår i: European Child and Adolescent Psychiatry, ISSN 1018-8827, E-ISSN 1435-165X, Vol. 25, nr 7, s. 673-676Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    n/a

  • 237.
    Andelin, M.
    et al.
    Department of Medicine, NU Hospital Group, Uddevalla, Sweden..
    Kropff, J.
    Department of Endocrinology, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands..
    Matuleviciene, V.
    Institute of Medicine, University of Gothenburg, Gothenburg, Sweden..
    Joseph, J.I.
    Department of Anaesthesiology, Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, PA, USA..
    Attvall, S.
    Institute of Medicine, University of Gothenburg, Gothenburg, Sweden..
    Theodorsson, Elvar
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk kemi.
    Hirsch, I.B.
    University of Washington, Seattle, WA, USA.
    Imberg, H.
    Statistiska Konsultgruppen, Gothenburg, Sweden..
    Dahlqvist, S.
    Department of Medicine, NU Hospital Group, Uddevalla, Sweden.
    Klonoff, D.
    Diabetes Research Institute, Mills-Peninsula Health Services, San Mateo, CA, USA..
    Haraldsson, B.
    Institute of Medicine, University of Gothenburg, Gothenburg, Sweden..
    DeVries, J.H.
    Department of Endocrinology, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands..
    Lind, M.
    Department of Medicine, NU Hospital Group, Uddevalla, Sweden Institute of Medicine, University of Gothenburg, Gothenburg, Sweden lind.marcus@telia.com..
    Assessing the Accuracy of Continuous Glucose Monitoring (CGM) Calibrated With Capillary Values Using Capillary or Venous Glucose Levels as a Reference.2016Ingår i: Journal of Diabetes Science and Technology, E-ISSN 1932-2968, Vol. 10, nr 4, s. 876-884Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Using the standard venous reference for the evaluation of continuous glucose monitoring (CGM) systems could possibly negatively affect measured CGM accuracy since CGM are generally calibrated with capillary glucose and venous and capillary glucose concentrations differ. We therefore aimed to quantify the effect of using capillary versus venous glucose reference samples on estimated accuracy in capillary calibrated CGM.less thanbr /greater thanMethods: We evaluated 41 individuals with type 1 diabetes mellitus (T1DM) using the Dexcom G4 CGM system over 6 days. Patients calibrated their CGM devices with capillary glucose by means of the HemoCue system. During 2 visits, capillary and venous samples were simultaneously measured by HemoCue and compared to concomitantly obtained CGM readings. The mean absolute relative difference (MARD) was calculated using capillary and venous reference samples.less thanbr /greater thanResults: Venous glucose values were 0.83 mmol/L (15.0 mg/dl) lower than capillary values over all glycemic ranges, P less than .0001. Below 4 mmol/l (72 mg/dl), the difference was 1.25 mmol/l (22.5 mg/dl), P = .0001, at 4-10 mmol/l (72-180 mg/dl), 0.67 mmol/l (12.0 mg/dl), P less than .0001 and above 10 mmol/l (180 mg/dl), 0.95 mmol/l (17.1 mg/dl), P less than .0001. MARD was 11.7% using capillary values as reference compared to 13.7% using venous samples, P = .037. Below 4 mmol/l (72 mg/dl) MARD was 16.6% and 31.8%, P = .048, at 4-10 mmol/l (72-180 mg/dl) 12.1% and 12.6%, P = .32, above 10 mmol/l (180 mg/dl) 8.7% and 9.2%, P = .82.less thanbr /greater thanConclusion: Using capillary glucose concentrations as reference to evaluate the accuracy of CGM calibrated with capillary samples is associated with a lower MARD than using venous glucose as the reference. Capillary glucose concentrations were significantly higher than venous in all glycemic ranges.less thanbr /greater than (© 2016 Diabetes Technology Society.)

  • 238.
    Andell, Pontus
    et al.
    Lund Univ, Sweden.
    Berntorp, Karolina
    Lund Univ, Sweden.
    Christiansen, Evald H.
    Aarhus Univ Hosp, Denmark.
    Gudmundsdottir, Ingibjorg J.
    Univ Hosp Iceland, Iceland.
    Sandhall, Lennart
    Helsingborg Hosp, Sweden.
    Venetsanos, Dimitrios
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Kardiologiska kliniken US.
    Erlinge, David
    Lund Univ, Sweden.
    Frobert, Ole
    Orebro Univ, Sweden.
    Koul, Sasha
    Lund Univ, Sweden.
    Reitan, Christian
    Lund Univ, Sweden.
    Gotberg, Matthias
    Lund Univ, Sweden.
    Reclassification of Treatment Strategy With Instantaneous Wave-Free Ratio and Fractional Flow Reserve A Substudy From the iFR-SWEDEHEART Trial2018Ingår i: JACC: Cardiovascular Interventions, ISSN 1936-8798, E-ISSN 1876-7605, Vol. 11, nr 20, s. 2084-2094Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVES The authors sought to compare reclassification of treatment strategy following instantaneous wave-free ratio (iFR) and fractional flow reserve (FFR). BACKGROUND iFR was noninferior to FFR in 2 large randomized controlled trials in guiding coronary revascularization. Reclassification of treatment strategy by FFR is well-studied, but similar reports on iFR are lacking. METHODS The iFR-SWEDEHEART (Instantaneous Wave-Free Ratio Versus Fractional Flow Reserve in Patients With Stable Angina Pectoris or Acute Coronary Syndrome Trial) study randomized 2,037 participants with stable angina or acute coronary syndrome to treatment guided by iFR or FFR. Interventionalists entered the preferred treatment (optimal medical therapy [OMT], percutaneous coronary intervention [PCI], or coronary artery bypass grafting [CABG]) on the basis of coronary angiograms, and the final treatment decision was mandated by the iFR/FFR measurements. RESULTS In the iFR/FFR (n = 1,009/n = 1,004) populations, angiogram-based treatment approaches were similar (p = 0.50) with respect to OMT (38%/35%), PCI of 1 (37%/39%), 2 (15%/16%), and 3 vessels (2%/2%) and CABG (8%/8%). iFR and FFR reclassified 40% and 41% of patients, respectively (p = 0.78). The majority of reclassifications were conversion of PCI to OMT in both the iFR/FFR groups (31.4%/29.0%). Reclassification increased with increasing number of lesions evaluated (odds ratio per evaluated lesion for FFR: 1.46 [95% confidence interval: 1.22 to 1.76] vs. iFR 1.37 [95% confidence interval: 1.18 to 1.59]). Reclassification rates for patients with 1, 2, and 3 assessed vessels were 36%, 52%, and 53% (p amp;lt; 0.01). CONCLUSIONS Reclassification of treatment strategy of intermediate lesions was common and occurred in 40% of patients with iFR or FFR. The most frequent reclassification was conversion from PCI to OMT regardless of physiology modality. Irrespective of the physiological index reclassification of angiogram-based treatment strategy increased with the number of lesions evaluated. (c) 2018 by the American College of Cardiology Foundation.

  • 239.
    Anders Eriksson, Mats
    et al.
    Karolinska Institute, Sweden; Karolinska University Hospital, Sweden; Gothenburg University, Sweden.
    Lieden, Agne
    Karolinska Institute, Sweden; Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
    Westerlund, Joakim
    Stockholm University, Sweden.
    Bremer, Anna
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk patologi och klinisk genetik. Division of Clinical Genetics, University Hospital, Link.
    Wincent, Josephine
    Karolinska Institute, Sweden; Karolinska Institute, Sweden.
    Sahlin, Ellika
    Karolinska Institute, Sweden; Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
    Gillberg, Christopher
    Gothenburg University, Sweden.
    Fernell, Elisabeth
    Gothenburg University, Sweden.
    Anderlid, Britt-Marie
    Karolinska Institute, Sweden; Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
    Rare copy number variants are common in young children with autism spectrum disorder2015Ingår i: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 104, nr 6, s. 610-618Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    AimSeveral studies have suggested that rare copy number variants (CNVs) are an important genetic contributor to autism spectrum disorders. The aims of the study were to use chromosomal microarray to investigate the presence of rare copy number variants in a population-based cohort of well-characterised young children with autism spectrum disorders and to relate the genetic results to neurodevelopmental profiles and medical conditions. MethodsWe performed chromosomal microarray on samples from 162 children who had been referred to the Stockholm Autism Centre for Young Children in Sweden after being diagnosed with autism spectrum disorder between 20 and 54months of age. ResultsPathogenic aberrations were detected in 8.6% of the children and variants of uncertain significance were present in another 8.6%. CNVs were more frequent in children with congenital malformations or dysmorphic features as well as in the subgroup with intellectual disability. ConclusionOur results support the use of chromosomal microarray methods for the first tier genetic analysis of autism spectrum disorder. However, it is likely in the near future that chromosomal microarray methods will probably be replaced by whole-exome and whole-genome sequencing technologies in clinical genetic testing.

  • 240.
    Andersen, Pia
    et al.
    Department of Research and Development, Region Kronoberg, Sweden.
    Holmberg, Sara
    Region Kronoberg, Sweden.
    Lendahls, Lena
    Department of Research and Development, Region Kronoberg, Sweden.
    Nilsen, Per
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för samhällsmedicin. Linköpings universitet, Medicinska fakulteten.
    Kristenson, Margareta
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för samhällsmedicin. Linköpings universitet, Medicinska fakulteten.
    Physical Activity on Prescription with Counsellor Support: A 4-Year Registry-Based Study in Routine Health Care in Sweden2018Ingår i: Healthcare, E-ISSN 2227-9032, Vol. 6, nr 2, artikel-id E34Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Public health gains from physical activity on prescription (PAP) depend on uptake in routine care. We performed an evaluation of the implementation, in a Swedish county council, of counsellors who give personalized support to PAP recipients aimed at facilitating PAP delivery. The aim was to compare characteristics between PAP recipients and the health care population as well as between PAP recipients who used and did not use counsellor support. We also investigated professional belonging and health care setting of health care professionals who prescribed PAP. 

    Methods: All patients’ ≥18 years who received PAP during 2009–2012 in primary and secondary care in the County Council of Kronoberg were included (n = 4879). Data were retrieved from electronic medical records. Main outcome measures were patient and professional characteristics. 

    Results: A third of the PAP recipients had diseases in ≥5 diagnostic groups and more than half had ≥11 office visits the year before receiving PAP. Counsellor support was used by one-third and PAP recipients who used counsellor support had more multiple diagnoses and office visits compared with non-users. Physicians issued 44% of prescriptions and primary care was the predominant setting. The amount of PAP did not change over time, but the proportion of physicians’ prescriptions decreased while the proportion of nurses’ prescriptions increased. 

    Conclusions: PAP recipients had high morbidity and were frequent health care attenders, indicating that PAP was predominantly used for secondary or tertiary prevention. PAP rates did not increase as intended after the implementation of counsellor support. View Full-Text

  • 241.
    Andersen, Pia
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för samhällsmedicin. Linköpings universitet, Tekniska fakulteten. Reg Kronoberg, Sweden.
    Lendahls, Lena
    Reg Kronoberg, Sweden; Linnaeus Univ, Sweden.
    Holmberg, Sara
    Reg Kronoberg, Sweden; Lund Univ, Sweden.
    Nilsen, Per
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för samhällsmedicin. Linköpings universitet, Medicinska fakulteten.
    Patients experiences of physical activity on prescription with access to counsellors in routine care: a qualitative study in Sweden2019Ingår i: BMC Public Health, ISSN 1471-2458, E-ISSN 1471-2458, Vol. 19, artikel-id 210Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BackgroundPhysical activity on prescription (PAP) has been implemented in several countries, including Sweden, to support patients who might benefit from increased physical activity. This study explores the experiences of recipients of PAP in routine health care in Sweden that offers the recipients support from physical activity counsellors. The aim was to explore influences on engagement in physical activity by PAP recipients from a long-term perspective.MethodsWe conducted individual semi-structured interviews using a topic guide with a purposively selected sample of 13 adult PAP recipients 1.5 to 2.5years after PAP. Interviews were recorded, transcribed verbatim and analysed through inductive and deductive content analysis. The questions were informed by Capability-Opportunity-Motivation-Behaviour (COM-B), which was also used as a framework to analyse the data by means of categorizing the factors (influences on the behaviour).ResultsTen factors (i.e. sub-categories) that influenced the participants engagement in physical activity were identified. PAP recipients capability to engage in physical activity was associated with adapting the PAP to the individuals physical capacity and taking into account the individuals previous experiences of physical activity. PAP recipients opportunity to engage in physical activity was related to receiving a prescription, receiving professional counselling and follow-up from a physical activity counsellor, collaboration between prescriber and counsellor, having access to appropriate activities, having a balanced life situation and having support from someone who encouraged continued physical activity. PAP recipients motivation to engage in physical activity was associated with the desire to improve his or her health condition and finding activities that encouraged continuation.ConclusionsPAP recipients engagement in physical activity was influenced by their capability, opportunity and motivation to undertake this behaviour. Numerous extraneous factors influence capability and motivation. Physical activity counsellors were found to be important for sustained activity because they use an individual approach to counselling and flexible follow-up adapted to each individuals need of support.

  • 242.
    Andersen, Åsa
    et al.
    Uppsala University, Sweden.
    Ståhl, Christian
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för samhällsmedicin. Linköpings universitet, Medicinska fakulteten.
    Anderzen, Ingrid
    Uppsala University, Sweden.
    Kristiansson, Per
    Uppsala University, Sweden.
    Larsson, Kjerstin
    Uppsala University, Sweden.
    Positive experiences of a vocational rehabilitation intervention for individuals on long-term sick leave, the Dirigo project: a qualitative study2017Ingår i: BMC Public Health, ISSN 1471-2458, E-ISSN 1471-2458, Vol. 17, artikel-id 790Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: The process of returning to work after long-term sick leave can sometimes be complex. Many factors, (e.g. cooperation between different authorities and the individual as well as individual factors such as health, emotional well-being and self-efficacy) may have an impact on an individuals ability to work. The aim of this study was to investigate clients experiences with an individually tailored vocational rehabilitation, the Dirigo project, and encounters with professionals working on it. The Dirigo project was based on collaboration between rehabilitation authorities, individually tailored interventions and a motivational interviewing approach. Methods: A descriptive qualitative design was used with data collected through interviews. Fourteen individuals on long-term sick leave took part in individual semi-structured interviews. The interviews were analysed using content analysis. Results: The analysis showed overall positive experience of methods and encounters with professionals in a vocational rehabilitation project. The positive experiences were based on four key factors: 1. Opportunities for receiving various dimensions of support. 2. Good overall treatment by the professionals. 3. Satisfaction with the working methods of the project, and 4. Opportunities for personal development. Conclusions: The main result showed that the clients had an overall positive experience of a vocational rehabilitation project and encounters with professionals who used motivational interviewing as a communication method. The overall positive experience indicated that their interactions with the different professionals may have affected their self-efficacy in general and in relation to transition to work. The knowledge is essential for the professionals working in the area of vocational rehabilitation. However, vocational rehabilitation interventions also need a societal approach to be able to offer clients opportunities for job training and real jobs.

  • 243.
    Anderson, Maria
    et al.
    Karolinska Inst, Sweden; Publ Dent Hlth Serv, Sweden; Ctr Pediat Oral Hlth, Sweden.
    Davidson, Thomas
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för hälso- och sjukvårdsanalys. Linköpings universitet, Medicinska fakulteten.
    Dahllof, Goran
    Karolinska Inst, Sweden; Ctr Pediat Oral Hlth, Sweden.
    Grindefjord, Margaret
    Karolinska Inst, Sweden; Publ Dent Hlth Serv, Sweden; Ctr Pediat Oral Hlth, Sweden.
    Economic evaluation of an expanded caries-preventive program targeting toddlers in high-risk areas in Sweden2019Ingår i: Acta Odontologica Scandinavica, ISSN 0001-6357, E-ISSN 1502-3850, Vol. 77, nr 4, s. 303-309Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: To economically evaluate a caries-preventive program "Stop Caries Stockholm" (SCS) where a standard program is supplemented with biannual applications of fluoride varnish in toddlers and compared it with the standard preventive program. Material and methods: Data from the cluster randomized controlled field trial SCS including 3403 children, conducted in multicultural areas with low socioeconomic status was used. The difference in mean caries increment between the examinations; when the toddlers were 1 and 3 years old, was outcome measure of the intervention. The program was evaluated from a societal as well as a dental health care perspective. The incremental cost-effectiveness ratio (ICER) was calculated as the incremental cost for each defs prevented. Results: Average dental health care costs per child at age 3 years were EUR 95.77 for the supplemental intervention and EUR 70.52 for the standard intervention. The ICER was EUR 280.56 from a dental health care perspective and EUR 468.67 and considered high. Conclusions: The supplemental caries intervention program was not found to be cost-effective. The program raised costs without significantly reducing caries development. A better alternative use of the resources is recommended. Trial registration: (ISRCTN35086887).

  • 244.
    Anderson, Peter
    et al.
    Newcastle University, England; Maastricht University, Netherlands.
    Bendtsen, Preben
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för samhällsmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Närsjukvården i västra Östergötland, Medicinska specialistkliniken.
    Spak, Fredrik
    University of Gothenburg, Sweden.
    Reynolds, Jillian
    Hospital Clin Barcelona, Spain.
    Drummond, Colin
    Kings Coll London, England; South London and Maudsley NHS Fdn Trust, England.
    Segura, Lidia
    Govt Catalonia, Spain.
    Keurhorst, Myrna N.
    Radboud University of Nijmegen, Netherlands.
    Palacio-Vieira, Jorge
    Govt Catalonia, Spain.
    Wojnar, Marcin
    Medical University of Warsaw, Poland.
    Parkinson, Kathryn
    Newcastle University, England.
    Colom, Joan
    Govt Catalonia, Spain.
    Kloda, Karolina
    Pomeranian Medical University, Poland.
    Deluca, Paolo
    Kings Coll London, England.
    Baena, Begona
    Govt Catalonia, Spain.
    Newbury-Birch, Dorothy
    Newcastle University, England.
    Wallace, Paul
    UCL, England.
    Heinen, Maud
    Radboud University of Nijmegen, Netherlands.
    Wolstenholme, Amy
    Kings Coll London, England.
    van Steenkiste, Ben
    Maastricht University, Netherlands.
    Mierzecki, Artur
    Pomeranian Medical University, Poland.
    Okulicz-Kozaryn, Katarzyna
    State Agency Prevent Alcohol Related Problems, Poland.
    Ronda, Gaby
    Maastricht University, Netherlands.
    Kaner, Eileen
    Newcastle University, England.
    Laurant, Miranda G. H.
    Radboud University of Nijmegen, Netherlands; HAN University of Appl Science, Netherlands.
    Coulton, Simon
    University of Kent, England.
    Gual, Toni
    Hospital Clin Barcelona, Spain.
    Improving the delivery of brief interventions for heavy drinking in primary health care: outcome results of the Optimizing Delivery of Health Care Intervention (ODHIN) five-country cluster randomized factorial trial2016Ingår i: Addiction, ISSN 0965-2140, E-ISSN 1360-0443, Vol. 111, nr 11, s. 1935-1945Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    AimTo test if training and support, financial reimbursement and option of referring screen-positive patients to an internet-based method of giving advice (eBI) can increase primary health-care providers delivery of Alcohol Use Disorders Identification Test (AUDIT)-C-based screening and advice to heavy drinkers. DesignCluster randomized factorial trial with 12-week implementation and measurement period. SettingPrimary health-care units (PHCU) in different locations throughout Catalonia, England, the Netherlands, Poland and Sweden. ParticipantsA total of 120 PHCU, 24 in each of Catalonia, England, the Netherlands, Poland and Sweden. InterventionsPHCUs were randomized to one of eight groups: care as usual, training and support (TS), financial reimbursement (FR) and eBI; paired combinations of TS, FR and eBI, and all of FR, TS and eBI. MeasurementsThe primary outcome measure was the proportion of eligible adult (age 18+ years) patients screened during a 12-week implementation period. Secondary outcome measures were proportion of screen-positive patients advised; and proportion of consulting adult patients given an intervention (screening and advice to screen-positives) during the same 12-week implementation period. FindingsDuring a 4-week baseline measurement period, the proportion of consulting adult patients who were screened for their alcohol consumption was 0.059 per PHCU (95% CI 0.034 to 0.084). Based on the factorial design, the ratio of the logged proportion screened during the 12-week implementation period was 1.48 (95% CI=1.13-1.95) in PHCU that received TS versus PHCU that did not receive TS; for FR, the ratio was 2.00 (95% CI=1.56-2.56). The option of referral to eBI did not lead to a higher proportion of patients screened. The ratio for TS plus FR was 2.34 (95% CI=1.77-3.10), and the ratio for TS plus FR plus eBI was1.68 (95% CI=1.11-2.53). ConclusionsProviding primary health-care units with training, support and financial reimbursement for delivering Alcohol Use Disorders Identification Test-C-based screening and advice to heavy drinkers increases screening for alcohol consumption. Providing primary health-care units with the option of referring screen-positive patients to an internet-based method of giving advice does not appear to increase screening for alcohol consumption.

  • 245.
    Anderson, Peter
    et al.
    Newcastle University, England; Maastricht University, Netherlands.
    Coulton, Simon
    University of Kent, England.
    Kaner, Eileen
    Newcastle University, England.
    Bendtsen, Preben
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för samhällsmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Närsjukvården i västra Östergötland, Medicinska specialistkliniken.
    Kloda, Karolina
    Pomeranian Medical University, Poland.
    Reynolds, Jillian
    Hospital Clin Barcelona, Spain.
    Segura, Lidia
    Govt Catalonia, Spain.
    Wojnar, Marcin
    Medical University of Warsaw, Poland.
    Mierzecki, Artur
    Pomeranian Medical University, Poland.
    Deluca, Paolo
    Kings Coll London, England.
    Newbury-Birch, Dorothy
    University of Teesside, England.
    Parkinson, Kathryn
    Newcastle University, England.
    Okulicz-Kozaryn, Katarzyna
    State Agency Prevent Alcohol Related Problems, Poland.
    Drummond, Colin
    Kings Coll London, England; South London and Maudsley NHS Fdn Trust, England.
    Gual, Antoni
    Hospital Clin Barcelona, Spain.
    Delivery of Brief Interventions for Heavy Drinking in Primary Care: Outcomes of the ODHIN 5-Country Cluster Randomized Trial2017Ingår i: Annals of family medicine (online), ISSN 1544-1709, E-ISSN 1544-1717, Vol. 15, nr 4, s. 335-340Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    PURPOSE We aimed to test whether 3 strategies-training and support, financial reimbursement, and an option to direct screen-positive patients to an Internet-based method of giving brief advice-have a longer-term effect on primary care clinicians delivery of screening and advice to heavy drinkers operationalized with the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) tool. METHODS We undertook a cluster randomized factorial trial with a 12-week implementation period in 120 primary health care units throughout Catalonia, England, Netherlands, Poland, and Sweden. Units were randomized to 8 groups: care as usual (control); training and support alone; financial reimbursement alone; electronic brief advice alone; paired combinations of these conditions; and all 3 combined. The primary outcome was the proportion of consulting adult patients (aged 18 years and older) receiving intervention-screening and, if screen-positive, advice-at 9 months. RESULTS Based on the factorial design, the ratio of the log of the proportion of patients given intervention at the 9-month follow-up was 1.39 (95% CI, 1.03-1.88) in units that received training and support as compared with units that did not. Neither financial reimbursement nor directing screen-positive patients to electronic brief advice led to a higher proportion of patients receiving intervention. CONCLUSIONS Training and support of primary health care units has a lasting, albeit small, impact on the proportion of adult patients given an alcohol intervention at 9 months.

  • 246.
    Anderson, Peter
    et al.
    Newcastle University, England; Maastricht University, Netherlands.
    Kaner, Eileen
    Newcastle University, England.
    Keurhorst, Myrna
    Radboud University of Nijmegen, Netherlands; Saxion University of Appl Science, Netherlands.
    Bendtsen, Preben
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för samhällsmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Närsjukvården i västra Östergötland, Medicinska specialistkliniken.
    van Steenkiste, Ben
    Maastricht University, Netherlands.
    Reynolds, Jillian
    IDIBAPS, Spain.
    Segura, Lidia
    Govt Catalonia, Spain.
    Wojnar, Marcin
    Medical University of Warsaw, Poland.
    Kloda, Karolina
    Pomeranian Medical University, Poland.
    Parkinson, Kathryn
    Newcastle University, England.
    Drummond, Colin
    Kings Coll London, England; Maudsley NHS Fdn Trust, England.
    Okulicz-Kozaryn, Katarzyna
    State Agency Prevent Alcohol Related Problems, Poland.
    Mierzecki, Artur
    Pomeranian Medical University, Poland.
    Laurant, Miranda
    Radboud University of Nijmegen, Netherlands; HAN University of Appl Science, Netherlands.
    Newbury-Birch, Dorothy
    University of Teesside, England.
    Gual, Antoni
    IDIBAPS, Spain.
    Attitudes and Learning through Practice Are Key to Delivering Brief Interventions for Heavy Drinking in Primary Health Care: Analyses from the ODHIN Five Country Cluster Randomized Factorial Trial2017Ingår i: International Journal of Environmental Research and Public Health, ISSN 1661-7827, E-ISSN 1660-4601, Vol. 14, nr 2, artikel-id 121Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    In this paper, we test path models that study the interrelations between primary health care provider attitudes towards working with drinkers, their screening and brief advice activity, and their receipt of training and support and financial reimbursement. Study participants were 756 primary health care providers from 120 primary health care units (PHCUs) in different locations throughout Catalonia, England, The Netherlands, Poland, and Sweden. Our interventions were training and support and financial reimbursement to providers. Our design was a randomized factorial trial with baseline measurement period, 12-week implementation period, and 9-month follow-up measurement period. Our outcome measures were: attitudes of individual providers in working with drinkers as measured by the Short Alcohol and Alcohol Problems Perception Questionnaire; and the proportion of consulting adult patients (age 18+ years) who screened positive and were given advice to reduce their alcohol consumption (intervention activity). We found that more positive attitudes were associated with higher intervention activity, and higher intervention activity was then associated with more positive attitudes. Training and support was associated with both positive changes in attitudes and higher intervention activity. Financial reimbursement was associated with more positive attitudes through its impact on higher intervention activity. We conclude that improving primary health care providers screening and brief advice activity for heavy drinking requires a combination of training and support and on-the-job experience of actually delivering screening and brief advice activity.

  • 247.
    Anderson, Peter
    et al.
    Newcastle Univ, England; Maastricht Univ, Netherlands.
    Kloda, Karolina
    Pomeranian Med Univ, Poland.
    Kaner, Eileen
    Newcastle Univ, England.
    Reynolds, Jillian
    Hosp Clin Barcelona, Spain.
    Bendtsen, Preben
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för samhällsmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Närsjukvården i västra Östergötland, Medicinska specialistkliniken.
    Pelgrum-Keurhorst, Myrna N.
    Radboud Univ Nijmegen, Netherlands; Saxion Univ Appl Sci, Netherlands.
    Segura, Lidia
    Govt Catalonia, Spain.
    Wojnar, Marcin
    Med Univ Warsaw, Poland.
    Mierzecki, Artur
    Pomeranian Med Univ, Poland.
    Deluca, Paolo
    King’s College London, London, UK.
    Newbury-Birch, Dorothy
    Teesside Univ, England.
    Parkinson, Kathryn
    Newcastle Univ, England; State Agcy Prevent Alcohol Related Problems, Poland.
    Okulicz-Kozaryn, Katarzyna
    State Agency for Prevention of Alcohol-Related Problems, Warsaw, Poland.
    Drummond, Colin
    Kings Coll London, England; South London and Maudsley NHS Fdn Trust, England.
    Laurant, Miranda G. H.
    Radboud Univ Nijmegen, Netherlands; HAN Univ Appl Sci, Netherlands.
    Gual, Antoni
    Neurosciences Institute, Hospital Clinic, IDIBAPS, Barcelona, Spain.
    Impact of practice, provider and patient characteristics on delivering screening and brief advice for heavy drinking in primary healthcare: Secondary analyses of data from the ODHIN five-country cluster randomized factorial trial2017Ingår i: European Journal of General Practice, ISSN 1381-4788, E-ISSN 1751-1402, Vol. 23, nr 1, s. 241-245Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: The implementation of primary healthcare-based screening and advice that is effective in reducing heavy drinking can be enhanced with training. Objectives: Undertaking secondary analysis of the five-country ODHIN study, we test: the extent to which practice, provider and patient characteristics affect the likelihood of patients being screened and advised; the extent to which such characteristics moderate the impact of training in increasing screening and advice; and the extent to which training mitigates any differences due to such characteristics found at baseline. Methods: A cluster randomized factorial trial involving 120 practices, 746 providers and 46 546 screened patients from Catalonia, England, the Netherlands, Poland, and Sweden. Practices were randomized to receive training or not to receive training. The primary outcome measures were the proportion of adult patients screened, and the proportion of screen-positive patients advised. Results: Nurses tended to screen more patients than doctors (OR = 3.1; 95% CI: 1.9, 4.9). Screenpositive patients were more likely to be advised by doctors than by nurses (OR = 2.3; 95% CI: 1.4, 4.1), and more liable to be advised the higher their risk status (OR = 1.9; 95% CI: 1.3, 2.7). Training increased screening and advice giving, with its impact largely unrelated to practice, provider or patient characteristics. Training diminished the differences between doctors and nurses and between patients with low or high-risk status. Conclusions: Training primary healthcare providers diminishes the negative impacts that some practice, provider and patient characteristics have on the likelihood of patients being screened and advised.

  • 248.
    Andersson, Anna-Maria
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    Mycobacterium tuberculosis and HIV coinfection: Effects on innate immunity and strategies to boost the immune response2019Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Tuberculosis (TB) still remains a big threat today, being the leading cause of death by a single infectious agent. The TB epidemic is fueled by HIV along with the increasing drug-resistance which prolongs the already long treatment duration and decreases the success rate for curing TB. In most cases an infection results in latency but HIV patients have a 20-30 times higher risk of developing active TB. There are around 36.9 million people living with HIV globally, with the highest burden in Africa. Although there are effective treatments against the disease, there is no cure for AIDS and the availability of the lifelong treatment is limited in low-income countries were the burden is highest. HIV infection causes an immunodeficiency characterized by the progressive loss of CD4 T cells which increases the risk of opportunistic infections, and infection by Mycobacterium tuberculosis (Mtb), the causative agent of TB. Mtb spreads through aerosols from one person with active tuberculosis to a healthy person. Upon inhalation the bacteria are phagocytosed by alveolar macrophages that secrete cytokines and chemokines to recruit more cells, such as dendritic cells, macrophages and lymphocytes, leading to the formation of a granuloma. During a single TB infection the bacteria are usually contained within the granuloma, but HIV can disrupt the stable granuloma, causing a rupture and dissemination of Mtb. This inflammatory site is also beneficial to HIV since it promotes replication of the virus within infected cells. HIV and Mtb are two successful intracellular pathogens able to avoid immune defense mechanisms both of the innate and adaptive immunity in order to persist and replicate. Their virulence factors can manipulate or inhibit cell signaling, phagosome maturation, autophagy, ROS production, apoptosis and antigen presentation, to promote survival. Boosting of immune defenses with host-directed therapies (HDT) has been proposed as a treatment strategy against TB, either alone or adjunctive to the current regimen.

    In this thesis, ways to boost the innate immune responses in Mtb and HIV coinfected macrophages were investigated, along with studies of the effect of HIV on Mtb antigen presentation in coinfected dendritic cells. The initial hypothesis was that autophagy induction through inhibition of mammalian target of rapamycin (mTOR) could suppress Mtb growth in HIV coinfected macrophages. However, during a low grade infection, autophagy induction increased Mtb replication due to a decreased autophagic flux and acidification of Mtb phagosomes. A general autophagic flux was induced, although not localized to the Mtb phagosomes, thus not inducing a xenophagy (autophagy of intracellular pathogens). Other ways of inducing autophagy or boosting the response in coinfected macrophages might be more beneficial and therefore the effect of efferocytosis was investigated. Uptake of apoptotic neutrophils by coinfected macrophages did not induce autophagy but enhanced the control of Mtb by other means. Upon efferocytosis, the macrophages acquired active myeloperoxidase (MPO) from the neutrophils that suppressed Mtb growth. The coinfected macrophages also produced more ROS after efferocytosis. The inhibition of Mtb growth could thus be mediated by MPO and the increased ROS production either directly or indirectly.

    The possibility to boost the innate immunity could prove to be important during an HIV coinfection, when the adaptive immunity is deficient. In addition to the well-known decline in CD4 T cells during the course of HIV progression, we found that HIV infection of dendritic cells inhibited antigen presentation by suppressing the expression of HLA-DR and co-stimulatory molecules on coinfected dendritic cells. Furthermore, HIV reduced secretion of pro-inflammatory cytokines and suppressed antigen processing through inhibition of autophagy. This impaired antigen presentation in coinfected dendritic cells resulted in a decreased activation and response of Mtb-specific CD4 T cells.

    In conclusion, this thesis shows how HIV can manipulate antigen presentation in Mtb coinfected dendritic cells and subsequently inhibit the adaptive immune response. It also contributes to insights on how efferocytosis of apoptotic neutrophils can boost the innate immune responses during coinfection. Lastly, autophagy induction through mTOR inhibition does not enhance protection against TB. Induction of autophagy should therefore be handled with care, particularly during HIV coinfection. 

    Delarbeten
    1. Autophagy induction targeting mTORC1 enhances Mycobacterium tuberculosis replication in HIV co-infected human macrophages
    Öppna denna publikation i ny flik eller fönster >>Autophagy induction targeting mTORC1 enhances Mycobacterium tuberculosis replication in HIV co-infected human macrophages
    Visa övriga...
    2016 (Engelska)Ingår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, nr 28171Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    To survive and replicate in macrophages Mycobacterium tuberculosis (Mtb) has developed strategies to subvert host defence mechanisms, including autophagy. Autophagy induction has the potential to clear Mtb, but little is known about its effect during controlled tuberculosis and HIV co-infection. Mammalian target of rapamycin complex1 (mTORC1) inhibitors were used to induce autophagy in human macrophages pre-infected with HIV-1(BaL) and infected with a low dose of Mtb (co-infected), or single Mtb infected (single infected). The controlled Mtb infection was disrupted upon mTOR inhibition resulting in increased Mtb replication in a dose-dependent manner which was more pronounced during co-infection. The increased Mtb replication could be explained by the marked reduction in phagosome acidification upon mTOR inhibition. Autophagy stimulation targeting mTORC1 clearly induced a basal autophagy with flux that was unlinked to the subcellular environment of the Mtb vacuoles, which showed a concurrent suppression in acidification and maturation/flux. Overall our findings indicate that mTOR inhibition during Mtb or HIV/Mtb co-infection interferes with phagosomal maturation, thereby supporting mycobacterial growth during low-dose and controlled infection. Therefore pharmacological induction of autophagy through targeting of the canonical mTORC1-pathway should be handled with caution during controlled tuberculosis, since this could have serious consequences for patients with HIV/Mtb co-infection.

    Ort, förlag, år, upplaga, sidor
    NATURE PUBLISHING GROUP, 2016
    Nationell ämneskategori
    Infektionsmedicin
    Identifikatorer
    urn:nbn:se:liu:diva-132355 (URN)10.1038/srep28171 (DOI)000384609100002 ()27302320 (PubMedID)
    Tillgänglig från: 2016-11-12 Skapad: 2016-11-01 Senast uppdaterad: 2019-03-28
    2. HIV Interferes with Mycobacterium tuberculosis Antigen Presentation in Human Dendritic Cells
    Öppna denna publikation i ny flik eller fönster >>HIV Interferes with Mycobacterium tuberculosis Antigen Presentation in Human Dendritic Cells
    Visa övriga...
    2016 (Engelska)Ingår i: American Journal of Pathology, ISSN 0002-9440, E-ISSN 1525-2191, Vol. 186, nr 12, s. 3083-3093Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    HIV coinfection is the most prominent risk factor for progression of Mycobacterium tuberculosis (Mtb) infection into active tuberculosis (TB) disease. The mechanisms behind the increased transition from latent to active TB in coinfected individuals have not been well elucidated at the cellular level. We hypothesized that HIV infection contributes to Mtb pathogenesis by interfering with the dendritic cell (DC) mediated immune control. Mtb-antigen processing and presentation are key events in the immune response against TB. Human immature DCs coinfected with HIV/Mtb had decreased expression of human leukocyte antigen antigen D related and the costimulatory molecules CD40, CD80, and CD86. In addition, Mtb-infected DCs triggered a significant release of the proinflammatory cytokines IL-6, IL-1 beta, and tumor necrosis factor-alpha, whereas coinfected DCs did not. To assess the DC antigen presentation capacity, we measured interferon-gamma from co-cultures of DCs and autologous Mtb antigen-specific CD4(+) T cells. Interferon-gamma release was significantly reduced when purified protein derivative- and Ag85B-specific CD4(+) T cells had been activated with coinfected DCs compared to Mtb-infected DCs, and this effect was attributed to Mtb antigen processing rather than peptide major histocompatibility complex class II loading. Evaluating autophagy as a measure of vesicular processing and maturation further revealed that HIV efficiently blocks initiation of this pathway during coinfection. Overall, our results demonstrate that HIV impairs Mtb antigen presentation in DCs, thereby suppressing an important cell linking innate and adaptive immune response in TB.

    Ort, förlag, år, upplaga, sidor
    ELSEVIER SCIENCE INC, 2016
    Nationell ämneskategori
    Immunologi inom det medicinska området
    Identifikatorer
    urn:nbn:se:liu:diva-133376 (URN)10.1016/j.ajpath.2016.08.003 (DOI)000389103800003 ()27746182 (PubMedID)
    Anmärkning

    Funding Agencies|Swedish Research Council [521-2012-1807, 348-2013-6588]; Swedish Heart-Lung Foundation [2014-0578]

    Tillgänglig från: 2016-12-27 Skapad: 2016-12-22 Senast uppdaterad: 2019-03-28
  • 249.
    Andersson, Anna-Maria
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    Andersson, Blanka
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    Lorell, Christoffer
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    Raffetseder, Johanna
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    Larsson, Marie
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    Blomgran, Robert
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    Autophagy induction targeting mTORC1 enhances Mycobacterium tuberculosis replication in HIV co-infected human macrophages2016Ingår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, nr 28171Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    To survive and replicate in macrophages Mycobacterium tuberculosis (Mtb) has developed strategies to subvert host defence mechanisms, including autophagy. Autophagy induction has the potential to clear Mtb, but little is known about its effect during controlled tuberculosis and HIV co-infection. Mammalian target of rapamycin complex1 (mTORC1) inhibitors were used to induce autophagy in human macrophages pre-infected with HIV-1(BaL) and infected with a low dose of Mtb (co-infected), or single Mtb infected (single infected). The controlled Mtb infection was disrupted upon mTOR inhibition resulting in increased Mtb replication in a dose-dependent manner which was more pronounced during co-infection. The increased Mtb replication could be explained by the marked reduction in phagosome acidification upon mTOR inhibition. Autophagy stimulation targeting mTORC1 clearly induced a basal autophagy with flux that was unlinked to the subcellular environment of the Mtb vacuoles, which showed a concurrent suppression in acidification and maturation/flux. Overall our findings indicate that mTOR inhibition during Mtb or HIV/Mtb co-infection interferes with phagosomal maturation, thereby supporting mycobacterial growth during low-dose and controlled infection. Therefore pharmacological induction of autophagy through targeting of the canonical mTORC1-pathway should be handled with caution during controlled tuberculosis, since this could have serious consequences for patients with HIV/Mtb co-infection.

  • 250.
    Andersson, B.
    et al.
    University of Gothenburg, Sweden.
    Swolin-Eide, D.
    University of Gothenburg, Sweden.
    Kristroem, B.
    Umeå University, Sweden.
    Gelander, L.
    University of Gothenburg, Sweden; Angered Hospital, Sweden.
    Magnusson, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Region Östergötland, Diagnostikcentrum, Klinisk kemi. Linköpings universitet, Medicinska fakulteten.
    Albertsson-Wikland, K.
    University of Gothenburg, Sweden.
    Seasonal variations in vitamin D in relation to growth in short prepubertal children before and during first year growth hormone treatment2015Ingår i: Journal of Endocrinological Investigation, ISSN 0391-4097, E-ISSN 1720-8386, Vol. 38, nr 12, s. 1309-1317Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose This study investigated the relationship between seasonal variations in 25-hydroxyvitamin D (25(OH) D) levels and growth in prepubertal children during both the pretreatment year and the first year of GH treatment. Methods The study included 249 short prepubertal children with a broad range of GH secretion, GH(max) during a 24 h profile median 23; range 1-127 mU/L, 191 boys (mean age +/- SD, 8.6 +/- 2.6 years), 58 girls (7.5 +/- 1.9 years) receiving GH treatment (mean 43 mu g/kg/day; range 17-99 mu g/kg/day). Serum 25(OH) D was measured using an automated IDS-iSYS immunoassay. Results 25(OH) D levels showed seasonal variation, and decreased significantly during GH treatment. 25(OH) D levels at start and first year reduction in 25(OH) D, correlated (-) with the first year growth response during treatment. The degree of GH secretion capacity within our study population of mainly non-GH deficient children and 25(OH) D sufficient (67 +/- 29 nmol/L) had no influence on 25(OH) D levels. Growth during GH treatment were independent of seasonal variations in 25(OH) D. Multiple regression analysis showed that 25(OH) D levels at treatment start, together with auxological data and IGF-binding protein-3(SDS), explained 61 % of the variation in first year gain in height(SDS). Conclusion 25(OH) D levels were associated with first year growth response to GH and may be a useful contribution to future growth prediction models.

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