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  • 51.
    Arbman, Gunnar
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Norrköping.
    Påhlman, Lars
    Uppsala University, Sweden.
    Glimelius, Bengt
    Uppsala University, Sweden / Karolinska Institutet, Stockholm, Sweden.
    The rise and fall of a longed for clinical trial in patients with generalized colorectal cancer2013In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 52, no 8, 1779-1782 p.Article in journal (Other academic)
  • 52.
    Arbman, Helena
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Familjerelationer i förändring? En studie av FFT-behandling avseende Frågor om Familjemedlemmar och Familjeklimat.2014Independent thesis Advanced level (professional degree), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    The paper is an evaluation of Functional Family Therapy (FFT). The aim was to investigate whether a FFT treatment meant a change for a youth and his parents regarding their description of family climate and dyads within the family. The target group consisted of 29 families that during 2011-2013 completed the FFT treatment at Ungdomscentrum (Youth Centre), in Uppsala community. The families had completed the self-assessment forms Issues of Family members and Family climate before and after the treatment. The results showed several significant differences that were consistent with previous research of the model, both internationally and nationally. Criticism and blame had been reduced between family members and the parents considered themselves less over-involved in their youth after the treatment. Current Family climate, it turned out that the adolescents, mothers and fathers experienced more closeness and less distance within the family in the end of treatment. The evaluation confirmed that the FFT- model provides some effect for families with a teenager with behavior problems. The strong emphasis on changing family patterns of communication to a more supportive one, is crucial for the family to complete their treatment and for the result of the treatment.

  • 53.
    Ardern, Clare
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Physiotherapy. Linköping University, Faculty of Health Sciences.
    Österberg, Annika
    Linköping University, Department of Medical and Health Sciences, Division of Physiotherapy. Linköping University, Faculty of Health Sciences. Uppsala Univ, Ctr Clin Res Sormland, Eskilstuna, Sweden.
    Tagesson (Sonesson), Sofi
    Linköping University, Department of Medical and Health Sciences, Division of Physiotherapy. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Gauffin, Håkan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Webster, Kate E.
    La Trobe University, Australia.
    Kvist, Joanna
    Linköping University, Department of Medical and Health Sciences, Division of Physiotherapy. Linköping University, Faculty of Health Sciences.
    The impact of psychological readiness to return to sport and recreational activities after anterior cruciate ligament reconstruction2014In: British Journal of Sports Medicine, ISSN 0306-3674, E-ISSN 1473-0480, Vol. 48, no 22, 1613-U50 p.Article in journal (Refereed)
    Abstract [en]

    Background This cross-sectional study aimed to examine whether appraisal of knee function, psychological and demographic factors were related to returning to the preinjury sport and recreational activity following anterior cruciate ligament (ACL) reconstruction. Method 164 participants completed a questionnaire battery at 1-7 years after primary ACL reconstruction. The battery included questionnaires evaluating knee self-efficacy, health locus of control, psychological readiness to return to sport and recreational activity, and fear of reinjury; and self-reported knee function in sport-specific tasks, knee-related quality of life and satisfaction with knee function. The primary outcome was returning to the preinjury sport or recreational activity. Results At follow-up, 40% (66/164) had returned to their preinjury activity. Those who returned had more positive psychological responses, reported better knee function in sport and recreational activities, perceived a higher knee-related quality of life and were more satisfied with their current knee function. The main reasons for not returning were not trusting the knee (28%), fear of a new injury (24%) and poor knee function (22%). Psychological readiness to return to sport and recreational activity, measured with the ACL-Return to Sport after Injury scale (was most strongly associated with returning to the preinjury activity). Age, sex and preinjury activity level were not related. Conclusions Less than 50% returned to their preinjury sport or recreational activity after ACL reconstruction. Psychological readiness to return to sport and recreation was the factor most strongly associated with returning to the preinjury activity. Including interventions aimed at improving this in postoperative rehabilitation programmes could be warranted to improve the rate of return to sport and recreational activities.

  • 54.
    Arnesen, Thomas
    et al.
    Haukeland Hospital, Norway .
    Glomnes, Nina
    University of Bergen, Norway .
    Stromsoy, Siri
    University of Bergen, Norway .
    Knappskog, Stian
    University of Bergen, Norway .
    Heie, Anette
    Haukeland Hospital, Norway .
    Akslen, Lars A.
    University of Bergen, Norway .
    Grytaas, Marianne
    Haukeland Hospital, Norway .
    Varhaug, Jan Erik
    Haukeland Hospital, Norway .
    Gimm, Oliver
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Brauckhoff, Michael
    Haukeland Hospital, Norway .
    Outcome after surgery for primary hyperaldosteronism may depend on KCNJ5 tumor mutation status: a population-based study from Western Norway2013In: Langenbeck's archives of surgery (Print), ISSN 1435-2443, E-ISSN 1435-2451, Vol. 398, no 6, 869-874 p.Article in journal (Refereed)
    Abstract [en]

    Primary aldosteronism (PA) is a frequent cause (about 10 %) of hypertension. Some cases of PA were recently found to be caused by mutations in the potassium channel KCNJ5. Our objective was to determine the mutation status of KCNJ5 and seven additional candidate genes for tumorigenesis: YY1, FZD4, ARHGAP9, ZFP37, KDM5C, LRP1B, and PDE9A and, furthermore, the surgical outcome of PA patients who underwent surgery in Western Norway. less thanbrgreater than less thanbrgreater thanTwenty-eight consecutive patients with aldosterone-producing adrenal tumors (20 patients with single adenoma, 8 patients with unilateral multiple adenomas or hyperplasia) who underwent surgery were included in this study. All patients were operated on by uncomplicated laparoscopic total adrenalectomy. Genomic DNA was isolated from tumor and non-tumor adrenocortical tissue, and DNA sequencing revealed the mutation status. less thanbrgreater than less thanbrgreater thanTen out of 28 (36 %) patients with PA displayed tumor mutations in KCNJ5 (p. G151R and L168R) while none were found in the corresponding non-tumor samples. No mutations were found in the other seven candidate genes screened. The presence of KCNJ5 mutations was associated with lower blood pressure and a higher chance for cure by surgery when compared to patients harboring the KCNJ5 wild type. less thanbrgreater than less thanbrgreater thanKCNJ5 mutations are associated with a better surgical outcome. Preoperative identification of the mutation status might have impact on surgical strategy (total vs. subtotal adrenalectomy).

  • 55.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Atypical fractures, a biased perspective2016In: Injury, ISSN 0020-1383, E-ISSN 1879-0267, Vol. 47, no 1, S28-S30 p.Article in journal (Refereed)
    Abstract [en]

    When stress fractures started to show up in the femurs of elderly ladies, it was soon evident that bisphosphonate use lay behind, and the absolute risk increase due to bisphosphonate use was reasonably well estimated already in 2008. Thereafter followed a period of confusion: the term atypical fracture was introduced, with a definition so vague that the true stress fractures tended to disappear in a cloud of ambiguity. This cast doubt on the association with bisphosphonates. The association was then re-established by large epidemiological studies based on radiographic adjudication. Atypical fractures are largely caused by bisphosphonates. With a correct indication, bisphosphonates prevent many more fractures than they cause, at least during the first years of use. With an incorrect indication they are likely to cause more harm than good. (C) 2016 Elsevier Ltd. All rights reserved.

  • 56.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Bone: Silk, metal and bone: why take implants out?2014In: Nature Reviews Rheumatology, ISSN 1759-4790, Vol. 10, no 7, 386-387 p.Article in journal (Other academic)
    Abstract [en]

    Degradable screws and plates for bone surgery have been produced from silk protein. The idea is to eliminate the need to take the implant out when the bone has healed. Will they provide sufficient strength, and will they degrade without causing inflammation? And why take implants out in the first place?

  • 57.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Editorial Material: ACADEMIC AUTHORSHIP How I was nearly duped into "authoring" a fake paper in BMJ-BRITISH MEDICAL JOURNAL, vol 351, issue h6605, pp2015In: BMJ-BRITISH MEDICAL JOURNAL, ISSN 1756-1833, Vol. 351, no h6605Article in journal (Other academic)
    Abstract [en]

    n/a

  • 58.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Editorial Material: Why do we operate proximal humeral fractures?2015In: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 86, no 3, 279-279 p.Article in journal (Other academic)
  • 59.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Mythbusting in Orthopedics challenges our desire for meaning2014In: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 85, no 6, 547-547 p.Article in journal (Other academic)
  • 60.
    Aspenberg, Per
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Malouf, Jorge
    Hospital San Pablo, Spain.
    Tarantino, Umberto
    University of Roma Tor Vergata, Italy.
    Garcia-Hernandez, Pedro A.
    University Hospital, Mexico.
    Corradini, Costantino
    University of Milan, Italy.
    Overgaard, Soren
    Odense University Hospital, Denmark; University of Southern Denmark, Denmark.
    Stepan, Jan J.
    Charles University of Prague, Czech Republic; Charles University of Prague, Czech Republic.
    Borris, Lars
    University Hospital, Denmark.
    Lespessailles, Eric
    CHR Orleans, France; University of Orleans, France.
    Frihagen, Frede
    Oslo University Hospital, Norway.
    Papavasiliou, Kyriakos
    Aristotle University of Thessaloniki, Greece.
    Petto, Helmut
    Eli Lilly, Austria.
    Ramon Caeiro, Jose
    University of Santiago de Compostela, Spain.
    Marin, Fernando
    Eli Lilly Research Centre, England.
    Effects of Teriparatide Compared with Risedronate on Recovery After Pertrochanteric Hip Fracture Results of a Randomized, Active-Controlled, Double-Blind Clinical Trial at 26 Weeks2016In: Journal of Bone and Joint Surgery. American volume, ISSN 0021-9355, E-ISSN 1535-1386, Vol. 98, no 22Article in journal (Refereed)
    Abstract [en]

    Background: Osteoporosis drugs might affect fracture-healing. We therefore studied the effects of teriparatide in comparison with risedronate on recovery after pertrochanteric hip fractures. Methods: The study was a randomized, multicenter, active-controlled, 78-week trial comparing teriparatide (20 mg/day) with risedronate (35 mg/week) initiated within 2 weeks after fixation of a low-trauma pertrochanteric hip fracture (AO/OTA 31-A1 or 31-A2). The main inclusion criteria were a bone mineral density T-score of amp;lt;=-22.0 and 25-OH-vitamin D of amp;gt;= 9.2 ng/mL. During the first 26 weeks, patients received study medication with oral or injectable placebo plus calcium and vitamin D in a double-blinded fashion. Secondary (Timed Up-and-Go [TUG] test, hip pain, Short Form [SF]-36 health status, and safety) and exploratory (radiographic outcomes and ability to walk) 26-week end points are reported. Results: Of the 224 patients who were randomized, 171 (86 teriparatide, 85 risedronate) were included in the analysis. The mean age was 77 +/- 8 years, 77% were female, and 26% had a prior history of low-trauma fracture. The teriparatide group completed the TUG test in a shorter time at 6, 12, 18, and 26 weeks (differences of 25.7, -4.4, -3.1, and -3.1 seconds, respectively; p = 0.021 for the overall difference). They also reported less pain on a visual analog scale immediately after the TUG test at 12 and 18 weeks (adjusted absolute differences of 10.6 and 11.9 mm, respectively; p amp;lt; 0.05). There were no significant between-group differences in the SF-36 score, Charnley hip pain score, ability to walk, or use of walking aids during follow-up. Radiographic healing at 6, 12, and 26 weeks, mechanical failure of the implant (teriparatide, 7; risedronate, 8), loss of reduction (teriparatide, 2; risedronate, 4), and nonunion (0 cases) were not significantly different. Mild hypercalcemia and hyperuricemia were more frequent with teriparatide. Conclusions: Teriparatide was associated with less pain and a shorter time to complete the TUG test between 6 and 26 weeks compared with risedronate. Other fracture-recovery outcomes were similar. The results should be interpreted with caution as these were secondary end points.

  • 61.
    Aspenberg, Per
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Schepull, Torsten
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Substantial creep in healing human Achilles tendons: A pilot study2015In: MLTJ Muscles, Ligaments and Tendons Journal, ISSN 2240-4554, Vol. 5, no 3, 151-155 p.Article in journal (Other academic)
    Abstract [en]

    Background: healing after rupture of the Achilles tendon can be described in terms of mechanical properties of the new-formed tissue, constituting the tendon callus. In previous human studies, the elastic modulus and the density remained almost constant during 3 months after mobilization started, and then improved up to one year. So far, time-dependent deformation of the healing human tendon has not been reported.

    Methods: in a series of 16 patients, operated with Achilles tendon suture, we implanted tantalum beads into the tendon and measured the distance between them repeatedly during 3 min of constant loading, using an ordinary image intensifier. The patients unloaded their leg for 30 min before the test. To avoid bias, all images were investigated in a randomized and blinded order.

    Results: total strain during 3 min of constant loading at 7 weeks post injury amounted to 5%, and at 19 weeks to 3%. About half of the strain, after the loading was applied, occurred during the second and third min. Considerable strain also occurred just before loading, when the patient was told that a load would be applied, but before this was actually done.

    Conclusion: the measurements were crude, and this study should be seen as a pilot. Still, viscoelastic properties seem to dominate the mechanical behavior the healing Achilles tendon from start of mobilization to 19 weeks, at least when tested after 30 min rest. This deserves further studies with more precise methods.

  • 62.
    Aspenberg, Per
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Schilcher, Jörg
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Atypical femoral fractures, bisphosphonates, and mechanical stress2014In: Current osteoporosis reports, ISSN 1544-1873, Vol. 12, no 2, 189-193 p.Article in journal (Refereed)
    Abstract [en]

    Atypical fractures are stress fractures occurring in the femoral shaft and closely related to bisphosphonate use. We here discuss their radiographic definition and different putative etiologies, apart from mechanical stress. Long time reduction of skeletal remodeling because of bisphosphonate use is thought to allow time for the bone to deteriorate mechanically, resulting in reduced toughness. However, the risk of atypical fracture diminishes rapidly after cessation of treatment, which suggests more acute effects of bisphosphonate use. Microdamage normally accumulates at areas of high stress. Possibly, ongoing bisphosphonate use reduces the ability to resorb and replace areas of microdamage by targeted remodeling. This could lead to crack propagation beyond a point of no return, ending in macroscopic stress fracture.

  • 63.
    Aspenberg, Per
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Schilcher, Jörg
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Stressfrakturer: hjulaxlar och idrottskarriärer brister2014In: Läkartidningen, ISSN 0023-7205, Vol. 111, no 36, 1436-1439 p.Article in journal (Refereed)
    Abstract [en]

    Stress fractures are caused by material fatigue. Microcracks appear normally in bone, and are dealt with by remodeling, specifically targeting areas of microdamage. Inhibition of targeted remodeling can allow microcracks to grow and form fractures. Intensive athletic training can lead to an increased microcrack formation rate, which exceeds what can be balanced by remodeling. Stress fractures often heal poorly, possibly because they are so thin: normal deformation of the bone during loading has been shown to lead to strains within thin cracks that are incompatible with cell survival. If the patient can't reduce loading sufficiently to allow healing, surgical stabilization will therefore be required. If the crack is transformed into a larger defect, e.g. by drilling a hole, strains will be reduced and healing facilitated by a simple procedure.

  • 64.
    Aspén-Franzén, Annika
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Föräldrars upplevelse av insatsen föräldrakoordinator.2014Independent thesis Advanced level (professional degree), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Parenting Coordination is a child-focused alternative dispute resolution approach practiced in Sweden since 2009. In this interview study separated parents experience of being supported in their parental cooperation by a parenting coordinator have been examined. Interviews have been conducted with seven parents who have had a Parenting Coordinator for at least six months. All participating parents have had several years of experience in an intractable conflict with the other parent, and has previously tried other forms of dispute solving measures. The results show that most parents have experienced that the method has been helpful when it comes to improving co-parenting skills, reducing conflict and improving the well-being of their children. The interviewed parents state that it has been most helpful to get support in structuring the communication with the other parent. Some say that having access to more information regarding common children improves parenting as well as the parent-child relationship. Not having to sit together in shared dialogue, getting help to make written agreements and the Parenting Coordinator having a clear child-focus in meetings are also addressed as helpful. Parents describe that in order to achieve said results it is important that the parenting-coordinator can remain neutral in the conflict.

  • 65.
    Atikuzzaman, Mohammad
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Seminal Influence on the Oviduct: Mating and/or semen components induce gene expression changes in the pre-ovulatory functional sperm reservoir in poultry and pigs2016Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Internal fertilization occurs in birds and eutherian mammals. Foetal development, however, is either extra- respectively intra-corpore (egg vs uterus). In these animal classes, the female genital tract stores ejaculated spermatozoa into a restricted oviductal segment; the functional pre-ovulatory sperm reservoir, where they survive until ovulation/s occur. Paradoxically, this immunologically foreign sperm suspension in seminal fluid/plasma, often microbiologically contaminated, ought to be promptly eliminated by the female local immune defence which, instead, tolerates its presence. The female immune tolerance is presumably signalled via a biochemical interplay of spermatozoa, as well as the peptides and proteins of the extracellular seminal fluid, with female epithelial and immune cells. Such interplay can result in gene expression shifts in the sperm reservoir in relation to variations in fertility. To further aid our understanding of the underlying mechanisms, this thesis studied the proteome of the seminal fluid (using 2D SDS-PAGE and mass spectrometry) including cytokine content (using Luminex and/or ELISA) of healthy, sexually mature and fertile boars and cocks. As well, gene expression changes (using cDNA microarray) in the oviductal sperm reservoirs of sexually-mature females, mated or artificially infused with homologous sperm-free seminal fluid/plasma were studied. Pigs were of commercial, fertility-selected modern breeds (Landrace), while chicken belonged to the ancestor Red Junglefowl (RJF, low egg laying-capacity), a selected egg-layer White Leghorn (WL) and of their Advanced Intercross Line (AIL). Ejaculates were manually collected as single sample in cocks or as the sperm-rich fraction [SRF] and the post- SRF fraction in boars to harvest seminal fluid/plasma for proteome/cytokine and infusion-studies. Oviducts were retrieved for gene-expression analyses via microarray immediately post-mortem (chicken) or at surgery (pig), 24 h after mating or genital infusion. In pigs, the protein-rich seminal plasma showed the highest amounts of cytokines [interferon-γ, interferon gamma-induced protein 10 (IP-10/CXCL10), macrophage derived chemokine (MDC/CCL22), growth-regulated oncogene (GRO/CXCL1), granulocyte-macrophage colony-stimulating factor (GM-CSF), monocyte chemo-attractant protein-1 (MCP-1/ CCL2), interleukin (IL)-6, IL-8/CXCL8, IL-10, IL-15, IL-17 and transforming growth factor (TGF)-β1-3) in the larger, protein-rich and sperm-poor post-SRF, indicating its main immune signalling influence. Chicken showed also a plethora of seminal fluid proteins with serum albumin and ovotransferrin being conserved through selection/evolution. However, they showed fewer cytokines than pigs, as the anti-inflammatory/immune-modulatory TGF-β2 or the pro-inflammatory CXCL10. The RJF contained fewer immune system process proteins and lacked TGF-β2 compared to WL and AIL, suggesting selection for increased fertility could be associated with higher expression of immune-regulating peptides/proteins. The oviductal sperm reservoir reacted in vivo to semen exposure. In chicken, mating significantly changed the expression of immune-modulatory and pH-regulatory genes in AIL. Moreover, modern fertile pigs (Landrace) and chicken (WL), albeit being taxonomically distant, shared gene functions for preservation of viable sperm in the oviduct. Mating or SP/SF-infusion were able to change the expression of comparable genes involved in pH-regulation (SLC16A2, SLC4A9, SLC13A1, SLC35F1, ATP8B3, ATP13A3) or immune-modulation (IFIT5, IFI16, MMP27, ADAMTS3, MMP3, MMP12). The results of the thesis demonstrate that both mating and components of the sperm-free seminal fluid/plasma elicit gene expression changes in the pre-ovulatory female sperm reservoir of chickens and pigs, some conserved over domestication and fertility-selection.

  • 66.
    Atikuzzaman, Mohammad
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Alvarez-Rodriguez, Manuel
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Carrillo, Alejandro Vicente
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Johnsson, Martin
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Wright, Dominic
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Rodriguez-Martinez, Heriberto
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Conserved gene expression in sperm reservoirs between birds and mammals in response to mating.2017In: BMC Genomics, ISSN 1471-2164, E-ISSN 1471-2164, Vol. 18, no 1Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Spermatozoa are stored in the oviductal functional sperm reservoir in animals with internal fertilization, including zoologically distant classes such as pigs or poultry. They are held fertile in the reservoir for times ranging from a couple of days (in pigs), to several weeks (in chickens), before they are gradually released to fertilize the newly ovulated eggs. It is currently unknown whether females from these species share conserved mechanisms to tolerate such a lengthy presence of immunologically-foreign spermatozoa. Therefore, global gene expression was assessed using cDNA microarrays on tissue collected from the avian utero-vaginal junction (UVJ), and the porcine utero-tubal junction (UTJ) to determine expression changes after mating (entire semen deposition) or in vivo cloacal/cervical infusion of sperm-free seminal fluid (SF)/seminal plasma (SP).

    RESULTS: In chickens, mating changed the expression of 303 genes and SF-infusion changed the expression of 931 genes, as compared to controls, with 68 genes being common to both treatments. In pigs, mating or SP-infusion changed the expressions of 1,722 and 1,148 genes, respectively, as compared to controls, while 592 genes were common to both treatments. The differentially expressed genes were significantly enriched for GO categories related to immune system functions (35.72-fold enrichment). The top 200 differentially expressed genes of each treatment in each animal class were analysed for gene ontology. In both pig and chicken, an excess of genes affecting local immune defence were activated, though frequently these were down-regulated. Similar genes were found in both the chicken and pig, either involved in pH-regulation (SLC16A2, SLC4A9, SLC13A1, SLC35F1, ATP8B3, ATP13A3) or immune-modulation (IFIT5, IFI16, MMP27, ADAMTS3, MMP3, MMP12).

    CONCLUSION: Despite being phylogenetically distant, chicken and pig appear to share some gene functions for the preservation of viable spermatozoa in the female reservoirs.

  • 67.
    Atikuzzaman, Mohammad
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Alvarez-Rodriguez, Manuel
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Vicente Carrillo, Alejandro
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Johnsson, Martin
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Wright, Dominic
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Rodriguez-Martinez, Heriberto
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Correction: Conserved gene expression in sperm reservoirs between birds and mammals in response to mating (vol 18, 98, 2017)2017In: BMC Genomics, ISSN 1471-2164, E-ISSN 1471-2164, Vol. 18, 563Article in journal (Refereed)
    Abstract [en]

    n/a

  • 68.
    Atikuzzaman, Mohammad
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Bhai Mehta, Ratnesh
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science.
    Fogelholm, Jesper
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Wright, Dominic
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Rodriguez-Martinez, Heriberto
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Mating induces the expression of immune- and pH-regulatory genes in the utero-vaginal junction containing mucosal sperm-storage tubuli of hens2015In: Reproduction, Vol. 150, no 6, 473-483 p.Article in journal (Refereed)
    Abstract [en]

    The female chicken, as with other species with internal fertilization, can tolerate the presence of spermatozoa within specialized sperm-storage tubuli (SST) located in the mucosa of the utero-vaginal junction (UVJ) for days or weeks, without eliciting an immune response. To determine if the oviduct alters its gene expression in response to sperm entry, segments from the oviduct (UVJ, uterus, isthmus, magnum and infundibulum) of mated and unmated (control) hens, derived from an advanced inter-cross line between Red Junglefowl and White Leghorn, were explored 24 h after mating using cDNA microarray analysis. Mating shifted the expression of fifteen genes in the UVJ (53.33% immune-modulatory and 20.00% pH-regulatory) and seven genes in the uterus, none of the genes in the latter segment overlapping the former (with the differentially expressed genes themselves being less related to immune-modulatory function). The other oviductal segments did not show any significant changes. These findings suggest sperm deposition causes a shift in expression in the UVJ (containing mucosal SST) and the uterus for genes involved in immune-modulatory and pH-regulatory functions, both relevant for sperm survival in the hen's oviduct.

  • 69.
    Atikuzzaman, Mohammad
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Sanz, Libia
    Instituto de Biomedicina de Valencia, CSIC, Valencia, Spain.
    Pla, Davinia
    Instituto de Biomedicina de Valencia, CSIC, Valencia, Spain.
    Alvarez-Rodriguez, Manuel
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Rubér, Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Wright, Dominic
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Calvete, Juan J.
    Instituto de Biomedicina de Valencia, CSIC, Valencia, Spain.
    Rodriguez-Martinez, Heriberto
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Selection for higher fertility reflects in the seminal fluid proteome of modern domestic chicken2017In: Comparative Biochemistry and Physiology - Part D: Genomics and Proteomics, ISSN 1744-117X, E-ISSN 1878-0407, Vol. 21, 27-40 p.Article in journal (Refereed)
    Abstract [en]

    The high egg-laying capacity of the modern domestic chicken (i.e. White Leghorn, WL) has arisen from the low egg-laying ancestor Red Junglefowl (RJF) via continuous trait selection and breeding. To investigate whether this long-term selection impacted the seminal fluid (SF)-proteome, 2DE electrophoresis-based proteomic analyses and immunoassays were conducted to map SF-proteins/cytokines in RJF, WL and a 9th generation Advanced Intercross Line (AIL) of RJF/WL-L13, including individual SF (n = 4, from each RJF, WL and AIL groups) and pools of the SF from 15 males of each group, analyzed by 2DE to determine their degree of intra-group (AIL, WL, and RJF) variability using Principal Component Analysis (PCA); respectively an inter-breed comparative analysis of intergroup fold change of specific SF protein spots intensity between breeds. The PCA clearly highlighted a clear intra-group similarity among individual roosters as well as a clear inter-group variability (e.g. between RJF, WL and AIL) validating the use of pools to minimize confounding individual variation. Protein expression varied considerably for processes related to sperm motility, nutrition, transport and survival in the female, including signaling towards immunomodulation. The major conserved SF-proteins were serum albumin and ovotransferrin. Aspartate aminotransferase, annexin A5, arginosuccinate synthase, glutathione S-transferase 2 and l-lactate dehydrogenase-A were RJF-specific. Glyceraldehyde-3-phosphate dehydrogenase appeared specific to the WL-SF while angiotensin-converting enzyme, γ-enolase, coagulation factor IX, fibrinogen α-chain, hemoglobin subunit α-D, lysozyme C, phosphoglycerate kinase, Src-substrate protein p85, tubulins and thioredoxin were AIL-specific. The RJF-SF contained fewer immune system process proteins and lower amounts of the anti-inflammatory/immunomodulatory TGF-β2 compared to WL and AIL, which had low levels- or lacked pro-inflammatory CXCL10 compared to RJF. The seminal fluid proteome differs between ancestor and modern chicken, with a clear enrichment of proteins and peptides related to immune-modulation for sperm survival in the female and fertility.

    The full text will be freely available from 2017-11-03 13:41
  • 70.
    Auffray, Charles
    et al.
    European Institute Syst Biol and Med, France; University of Lyon, France.
    Balling, Rudi
    University of Luxembourg, Luxembourg.
    Barroso, Ines
    Wellcome Trust Sanger Institute, England.
    Bencze, Laszlo
    Semmelweis University, Hungary.
    Benson, Mikael
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Allergy Center.
    Bergeron, Jay
    Pfizer Inc, MA 02139 USA.
    Bernal-Delgado, Enrique
    IACS IIS Aragon, Spain.
    Blomberg, Niklas
    EL IXIR, England.
    Bock, Christoph
    Austrian Academic Science, Austria; Medical University of Vienna, Austria; Max Planck Institute Informat, Germany.
    Conesa, Ana
    Principe Felipe Research Centre, Spain; University of Florida, FL 32610 USA.
    Del Signore, Susanna
    Bluecompan Ltd, England.
    Delogne, Christophe
    KPMG Luxembourg, Luxembourg.
    Devilee, Peter
    Leiden University, Netherlands.
    Di Meglio, Alberto
    European Org Nucl Research CERN, Switzerland.
    Eijkemans, Marinus
    University of Utrecht, Netherlands.
    Flicek, Paul
    European Bioinformat Institute EMBL EBI, England.
    Graf, Norbert
    University of Saarland, Germany.
    Grimm, Vera
    Forschungszentrum Julich, Germany.
    Guchelaar, Henk-Jan
    Leiden University, Netherlands.
    Guo, Yi-Ke
    University of London Imperial Coll Science Technology and Med, England.
    Glynne Gut, Ivo
    BIST, Spain.
    Hanbury, Allan
    TU Wien, Austria.
    Hanif, Shahid
    Assoc British Pharmaceut Ind, England.
    Hilgers, Ralf-Dieter
    University of Klinikum Aachen, Germany.
    Honrado, Angel
    SYNAPSE Research Management Partners, Spain.
    Rod Hose, D.
    University of Sheffield, England.
    Houwing-Duistermaat, Jeanine
    University of Leeds, England.
    Hubbard, Tim
    Kings Coll London, England; Genom England, England.
    Helen Janacek, Sophie
    European Bioinformat Institute EMBL EBI, England.
    Karanikas, Haralampos
    University of Athens, Greece.
    Kievits, Tim
    Vitr Healthcare Holding BV, Netherlands.
    Kohler, Manfred
    Fraunhofer Institute Molecular Biol and Appl Ecol ScreeningPor, Germany.
    Kremer, Andreas
    ITTM SA, Luxembourg.
    Lanfear, Jerry
    Pfizer Ltd, England.
    Lengauer, Thomas
    Max Planck Institute for Informatics, Saarbrucken, Germany.
    Maes, Edith
    Health Econ and Outcomes Research, Belgium.
    Meert, Theo
    Janssen Pharmaceut NV, Belgium.
    Mueller, Werner
    University of Manchester, England.
    Nickel, Dorthe
    Institute Curie, France.
    Oledzki, Peter
    Linguamat Ltd, England.
    Pedersen, Bertrand
    PwC Luxembourg, Luxembourg.
    Petkovic, Milan
    Philips, Netherlands.
    Pliakos, Konstantinos
    KU Leuven Kulak, Belgium.
    Rattray, Magnus
    University of Manchester, England.
    Redon i Mas, Josep
    University of Valencia, Spain.
    Schneider, Reinhard
    University of Luxembourg, Luxembourg.
    Sengstag, Thierry
    SIB, Switzerland; University of Basel, Switzerland.
    Serra-Picamal, Xavier
    Agency Health Qual and Assessment Catalonia AQuAS, Spain.
    Spek, Wouter
    EuroBioForum Fdn, Netherlands.
    Vaas, Lea A. I.
    Fraunhofer Institute Molecular Biol and Appl Ecol ScreeningPor, Germany.
    van Batenburg, Okker
    EuroBioForum Fdn, Netherlands.
    Vandelaer, Marc
    Integrated BioBank Luxembourg, Luxembourg.
    Varnai, Peter
    Technopolis Grp, England.
    Villoslada, Pablo
    Hospital Clin Barcelona, Spain.
    Antonio Vizcaino, Juan
    European Bioinformat Institute EMBL EBI, England.
    Peter Mary Wubbe, John
    European Platform Patients Org Science and Ind Epposi, Belgium.
    Zanetti, Gianluigi
    CRS4, Italy; BBMRI ERIC, Austria.
    Making sense of big data in health research: Towards an EU action plan2016In: Genome Medicine, ISSN 1756-994X, E-ISSN 1756-994X, Vol. 8, no 71Article in journal (Refereed)
    Abstract [en]

    Medicine and healthcare are undergoing profound changes. Whole-genome sequencing and high-resolution imaging technologies are key drivers of this rapid and crucial transformation. Technological innovation combined with automation and miniaturization has triggered an explosion in data production that will soon reach exabyte proportions. How are we going to deal with this exponential increase in data production? The potential of "big data" for improving health is enormous but, at the same time, we face a wide range of challenges to overcome urgently. Europe is very proud of its cultural diversity; however, exploitation of the data made available through advances in genomic medicine, imaging, and a wide range of mobile health applications or connected devices is hampered by numerous historical, technical, legal, and political barriers. European health systems and databases are diverse and fragmented. There is a lack of harmonization of data formats, processing, analysis, and data transfer, which leads to incompatibilities and lost opportunities. Legal frameworks for data sharing are evolving. Clinicians, researchers, and citizens need improved methods, tools, and training to generate, analyze, and query data effectively. Addressing these barriers will contribute to creating the European Single Market for health, which will improve health arid healthcare for all Europearis.

  • 71.
    Auffray, Charles
    et al.
    European Institute Syst Biol and Med, France; University of Lyon, France.
    Balling, Rudi
    University of Luxembourg, Luxembourg.
    Barroso, Ines
    Wellcome Trust Sanger Institute, England.
    Bencze, Laszlo
    Semmelweis University, Hungary.
    Benson, Mikael
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Allergy Center.
    Bergeron, Jay
    Pfizer Inc, MA 02139 USA.
    Bernal-Delgado, Enrique
    IACS IIS Aragon, Spain.
    Blomberg, Niklas
    ELIXIR, England.
    Bock, Christoph
    Austrian Academic Science, Austria; Austrian Academic Science, Austria; Max Planck Institute Informat, Germany.
    Conesa, Ana
    Principe Felipe Research Centre, Spain; University of Florida, FL 32610 USA.
    Del Signore, Susanna
    Bluecompan Ltd, England.
    Delogne, Christophe
    KPMG Luxembourg, Luxembourg.
    Devilee, Peter
    Leiden University, Netherlands.
    Di Meglio, Alberto
    European Org Nucl Research, Switzerland.
    Eijkemans, Marinus
    University of Medical Centre Utrecht, Netherlands.
    Flicek, Paul
    EMBL EBI, England.
    Graf, Norbert
    University of Saarland, Germany.
    Grimm, Vera
    Forschungszentrum Julich, Germany.
    Guchelaar, Henk-Jan
    Leiden University, Netherlands.
    Guo, Yi-Ke
    Imperial Coll London, England.
    Glynne Gut, Ivo
    BIST, Spain.
    Hanbury, Allan
    TU Wien, Austria.
    Hanif, Shahid
    Assoc British Pharmaceut Ind, England.
    Hilgers, Ralf-Dieter
    Rhein Westfal TH Aachen, Germany.
    Honrado, Angel
    SYNAPSE Research Management Partners, Spain.
    Rod Hose, D.
    University of Sheffield, England.
    Houwing-Duistermaat, Jeanine
    University of Leeds, England.
    Hubbard, Tim
    Kings Coll London, England; Genom England, England.
    Helen Janacek, Sophie
    EMBL EBI, England.
    Karanikas, Haralampos
    University of Athens, Greece.
    Kievits, Tim
    Vitromics Healthcare Holding BV, Netherlands.
    Kohler, Manfred
    Fraunhofer Institute Molecular Biol and Appl Ecol ScreeningPor, Germany.
    Kremer, Andreas
    ITTM SA, Luxembourg.
    Lanfear, Jerry
    Pfizer Ltd, England.
    Lengauer, Thomas
    Max Planck Institute Informat, Germany.
    Maes, Edith
    Deloitte Belgium, Belgium.
    Meert, Theo
    Janssen Pharmaceut NV, Belgium.
    Muller, Werner
    University of Manchester, England.
    Nickel, Dothe
    Institute Curie, France.
    Oledzki, Peter
    Linguamat Ltd, England.
    Pedersen, Bertrand
    PwC Luxembourg, Luxembourg.
    Petkovic, Milan
    Philips, Netherlands.
    Pliakos, Konstantinos
    KU Leuven Kulak, Belgium.
    Rattray, Magnus
    University of Manchester, England.
    Redon i Mas, Josep
    University of Valencia, Spain.
    Schneider, Reinhard
    University of Luxembourg, Luxembourg.
    Sengstag, Thierry
    SIB, Switzerland; University of Basel, Switzerland.
    Serra-Picamal, Xavier
    Agency Health Qual and Assessment Catalonia AQuAS, Spain.
    Spek, Wouter
    EuroBioForum Fdn, Netherlands.
    Vaas, Lea A. I.
    Fraunhofer Institute Molecular Biol and Appl Ecol ScreeningPor, Germany.
    van Batenburg, Okker
    EuroBioForum Fdn, Netherlands.
    Vandelaer, Marc
    Integrated BioBank Luxembourg, Luxembourg.
    Varnai, Peter
    Technopolis Grp, England.
    Villoslada, Pablo
    Hospital Clin Barcelona, Spain.
    Antonio Vizcaino, Juan
    EMBL EBI, England.
    Peter Mary Wubbe, John
    Epposi, Belgium.
    Zanetti, Gianluigi
    CRS4, Italy; BBMRI ERIC, Austria.
    Correction: Making sense of big data in health research: towards an EU action plan (vol 8, pg 71, 2016)2016In: Genome Medicine, ISSN 1756-994X, E-ISSN 1756-994X, Vol. 8, 118Article in journal (Other academic)
    Abstract [en]

    n/a

  • 72.
    Avall Lundqvist, Elisabeth
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Nordström, L
    Sjövall, K
    Eneroth, P
    Evaluation of seven different tumour markers for the establishment of tumour marker panels in gynecologic malignancies.1989In: European journal of gynaecological oncology, ISSN 0392-2936, Vol. 10, no 6, 395-405 p.Article in journal (Refereed)
    Abstract [en]

    Seven tumour markers, i.e. squamous cell carcinoma antigen (SCC), cancer antigen 125 (CA 125), tissue polypeptide antigen (TPA), neopterin, C-reactive protein (CRP), carcinoembryonic antigen (CEA) and deoxythymidine kinase (TK) were analysed in sera from 104 women with benign and 61 women with malignant gynecologic diseases, in order to create tumour marker panels for various gynecologic malignancies, for monitoring and prediction of disease development. The incidence of elevated tumour marker levels, in cervical carcinoma was 78% when SCC, CA 125 and CEA were used. In ovarian carcinoma one of the markers CA 125, TPA and CEA was elevated in 91% and for endometrial carcinoma the best combination of markers was SCC, CA 125 and CEA (57%). No individual marker was superior to the above combinations. However, in patients with a fatal outcome of their malignant gynecologic disease (mean survival time from serum sampling was 16 months), the incidence of death was highest among those who had TPA elevated (91%) followed by neopterin (86%) and CRP (76%). Although intercurrent diseases affected tumour marker levels the markers picked up a majority of patients with a poor prognosis. This demonstrates the importance of interpreting tumour marker results against a background of detailed clinical information.

  • 73.
    Avall-Lundqvist, E H
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Department of Gynecologic Oncology, Karolinska Hospital, Stockholm, Sweden.
    Peterson, C O
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences.
    Serum cholesterol and apolipoprotein B levels may reflect disease activity in ovarian cancer patients.1996In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 35, no 8, 1007-10 p.Article in journal (Refereed)
    Abstract [en]

    Data in the literature demonstrates increased receptor-mediated uptake of low density lipoprotein (LDL) in many types of malignant cells compared with normal cells. In acute leukemia, an inverse correlation has been demonstrated between disease activity and plasma cholesterol. To explore whether this is true also for ovarian cancer a case-control study was performed. We serially collected blood samples and assayed serum cholesterol and apolipoprotein B (the receptor recognizing moiety of LDL) in 10 patients with ovarian cancer. At diagnosis, the patients had lower mean cholesterol levels compared with 6 healthy women. An increase was found after primary surgery and after successful initial chemotherapy. The 5 patients who are in complete remission after a mean follow-up time of 79 months had higher cholesterol and apolipoprotein B levels at their last visit than at diagnosis. In contrast, a reduction of the two analytes was found in the patients who died from their ovarian cancer 15 to 28 months after diagnosis. The results may open a possibility for targetted chemotherapy in ovarian cancer with LDL as a drug carrier.

  • 74.
    Avall-Lundqvist, Elisabeth
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Department of Obstetrics and Gynecology, Karolinska Hospital, Stockholm, Sweden.
    Sjövall, K
    Hansson, L O
    Eneroth, P
    Peri- and postoperative changes in serum levels of four tumor markers and three acute phase reactants in benign and malignant gynecological diseases.1992In: Archives of Gynecology and Obstetrics, ISSN 0932-0067, E-ISSN 1432-0711, Vol. 251, no 2, 69-78 p.Article in journal (Refereed)
    Abstract [en]

    Serum levels of squamous cell carcinoma antigen, carcinoembryonic antigen, CA 125, tissue polypeptide antigen, CRP, alpha 1-antitrypsin and haptoglobin were determined peri- and postoperatively in patients undergoing surgery for benign gynecological disease (n = 18) and postoperatively in women operated for cervical carcinoma (n = 23). The only significant changes seen after premedication, during anesthesia and during surgery were a decrease in serum concentrations of alpha 1-antitrypsin and haptoglobin. We found no postoperative changes in the serum levels of squamous cell carcinoma antigen nor in carcinoembryonic antigen values. However, the latter analyte was influenced by smoking habits. Elevated levels of CA 125 and tissue polypeptide antigen were found in the cancer patients, predominantly within the first 1-3 weeks after surgery. These levels decreased to normal values within 4-6 weeks postoperatively. The median intraindividual coefficients of variation for the tumor markers ranged between 15% and 28% in 30 control women not having surgery. In general, it would seem advisable to wait 6 weeks after surgery before monitoring with CA 125 and TPA is started.

  • 75.
    Axelsson, Daniel
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences. Ryhov County Hospital, Sweden.
    Blomberg, Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Prevalence of postpartum infections: a population-based observational study2014In: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 93, no 10, 1065-1068 p.Article in journal (Refereed)
    Abstract [en]

    We investigated the prevalence of postpartum infections among women giving birth during 1year in a population-based observational/questionnaire study at seven hospitals in the southeast region of Sweden. Of the women greater than99% (n=11124) received a questionnaire to inquire if they had endometritis, mastitis, or wound, urinary tract or any other infection within 2months postpartum and whether they received antibiotics for this. Prevalence rates for infections and antibiotic treatment were estimated. The response rate was 60.1%. At least one infectious episode was reported by 10.3% of the women and 7.5% had received antibiotics. The prevalence for infections with and without antibiotics were, respectively, mastitis 4.7% and 2.9%, urinary tract infection 3.0% and 2.4%, endometritis 2.0% and 1.7%, wound infection 1.8% and 1.2%. There was no inter-county difference in infection prevalence. Clinical postpartum infections in a high-resource setting are relatively common.

  • 76.
    Axelsson, Stina
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Cheramy, Mikael
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Åkerman, Linda
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Pihl, Mikael
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Ludvigsson, Johnny
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Casas, Rosaura
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Cellular and Humoral Immune responses in Type 1 Diabetic patients participating in a Phase III GAD-alum Intervention Trial2013In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 36, no 11, 3418-3424 p.Article in journal (Refereed)
    Abstract [en]

    OBJECTIVEGAD formulated in aluminum hydroxide (GAD-alum) has previously been shown to induce preservation of residual insulin secretion in recent-onset type 1 diabetes, but recent phase II and III GAD-alum trials failed to reach primary outcomes. The European phase III study was therefore closed after 15 months, and only a minority of patients completed the 30 months of follow-up.RESEARCH DESIGN AND METHODSThis study aimed to characterize cellular and humoral responses in the Swedish patients (n = 148) participating in the phase III trial, receiving four (4D) or two (2D) GAD-alum doses or placebo. Serum GAD(65) antibody (GADA) levels, GADA IgG1-4 subclass distribution, cytokine secretion, and proliferative responses in peripheral blood mononuclear cells (PBMCs) were analyzed.RESULTSThe GAD(65)-induced cytokine profile tended to switch toward a predominant Th2-associated profile over time both in the 2D and 4D group. The groups also displayed increased GADA levels and PBMC proliferation compared with placebo, whereas GADA IgG subclass distribution changed in 4D patients.CONCLUSIONSBoth 2D and 4D patients displayed GAD(65)-specifc cellular and humoral effects after GAD-alum treatment, but at different time points and magnitudes. No specific immune markers could be associated with treatment efficacy.

  • 77.
    Ayers, S.
    et al.
    City University of London, England.
    Bond, R.
    University of Sussex, England.
    Bertullies, S.
    City University of London, England.
    Wijma, Klaas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    The aetiology of post-traumatic stress following childbirth: a meta-analysis and theoretical framework2016In: Psychological Medicine, ISSN 0033-2917, E-ISSN 1469-8978, Vol. 46, no 6, 1121-1134 p.Article, review/survey (Refereed)
    Abstract [en]

    There is evidence that 3.17% of women report post-traumatic stress disorder (PTSD) after childbirth. This meta-analysis synthesizes research on vulnerability and risk factors for birth-related PTSD and refines a diathesis-stress model of its aetiology. Systematic searches were carried out on PsycINFO, PubMed, Scopus and Web of Science using PTSD terms crossed with childbirth terms. Studies were included if they reported primary research that examined factors associated with birth-related PTSD measured at least 1 month after birth. In all, 50 studies (n = 21 429) from 15 countries fulfilled inclusion criteria. Pre-birth vulnerability factors most strongly associated with PTSD were depression in pregnancy (r = 0.51), fear of childbirth (r = 0.41), poor health or complications in pregnancy (r = 0.38), and a history of PTSD (r = 0.39) and counselling for pregnancy or birth (r = 0.32). Risk factors in birth most strongly associated with PTSD were negative subjective birth experiences (r = 0.59), having an operative birth (assisted vaginal or caesarean, r = 0.48), lack of support (r = -0.38) and dissociation (r = 0.32). After birth, PTSD was associated with poor coping and stress (r = 0.30), and was highly co-morbid with depression (r = 0.60). Moderator analyses showed that the effect of poor health or complications in pregnancy was more apparent in high-risk samples. The results of this meta-analysis are used to update a diathesis-stress model of the aetiology of postpartum PTSD and can be used to inform screening, prevention and intervention in maternity care.

  • 78.
    Back, Christina
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Child and Adolescent Psychiatry in Linköping.
    Gustafsson, Per A.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Child and Adolescent Psychiatry in Linköping.
    Berterö, Carina
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Health Sciences.
    Parental opinions of their child's experience in the legal process: an interpretative analysis2014In: Journal of Child Sexual Abuse, ISSN 1053-8712, E-ISSN 1547-0679, Vol. 23, no 3, 290-303 p.Article in journal (Refereed)
    Abstract [en]

    The aim of this study is to demonstrate how parents of children who are victims of sexual assault experience the legal process from the children’s and parents’ perspective. Nine parents, identified in the records of three public prosecution offices in three cities in Sweden, were interviewed. The parents described feelings of shame and guilt over what their children had experienced. They felt stigmatized and had difficulty fulfilling their parental role, perceived a lack of information and support from the professionals involved, and experienced a sense of withdrawal from their role as parents, though they felt the professionals who worked with their children were helpful and influential.

  • 79.
    Bajuri, M. N.
    et al.
    University of Oxford, England; University of Teknol Malaysia, Malaysia.
    Isaksson, Hanna
    Lund University, Sweden.
    Eliasson, Pernilla T.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Thompson, Mark S.
    University of Oxford, England.
    A hyperelastic fibre-reinforced continuum model of healing tendons with distributed collagen fibre orientations2016In: Biomechanics and Modeling in Mechanobiology, ISSN 1617-7959, E-ISSN 1617-7940, Vol. 15, no 6, 1457-1466 p.Article in journal (Refereed)
    Abstract [en]

    The healing process of ruptured tendons is problematic due to scar tissue formation and deteriorated material properties, and in some cases, it may take nearly a year to complete. Mechanical loading has been shown to positively influence tendon healing; however, the mechanisms remain unclear. Computational mechanobiology methods employed extensively to model bone healing have achieved high fidelity. This study aimed to investigate whether an established hyperelastic fibre-reinforced continuum model introduced by Gasser, Ogden and Holzapfel (GOH) can be used to capture the mechanical behaviour of the Achilles tendon under loading during discrete timepoints of the healing process and to assess the models sensitivity to its microstructural parameters. Curve fitting of the GOH model against experimental tensile testing data of rat Achilles tendons at four timepoints during the tendon repair was used and achieved excellent fits (0.9903 amp;lt; R-2 amp;lt; 0.9986). A parametric sensitivity study using a three-level central composite design, which is a fractional factorial design method, showed that the collagen-fibre-related parameters in the GOH model-kappa, k(1) and k(2)-had almost equal influence on the fitting. This study demonstrates that the GOH hyperelastic fibre-reinforced model is capable of describing the mechanical behaviour of healing tendons and that further experiments should focus on establishing the structural and material parameters of collagen fibres in the healing tissue.

  • 80.
    Balao da Silva, C. M.
    et al.
    Vet Teaching Hospital, Spain.
    Ortega-Ferrusola, C.
    Vet Teaching Hospital, Spain.
    Morrell, J. M.
    Swedish University of Agriculture Science, Sweden.
    Rodriguez-Martinez, Heriberto
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Pena, F. J.
    Vet Teaching Hospital, Spain.
    Flow Cytometric Chromosomal Sex Sorting of Stallion Spermatozoa Induces Oxidative Stress on Mitochondria and Genomic DNA2016In: Reproduction in domestic animals (1990), ISSN 0936-6768, E-ISSN 1439-0531, Vol. 51, no 1, 18-25 p.Article in journal (Refereed)
    Abstract [en]

    To date, the only repeatable method to select spermatozoa for chromosomal sex is the Beltsville sorting technology using flow cytometry. Improvement of this technology in the equine species requires increasing awareness of the modifications that the sorting procedure induces on sperm intactness. Oxidative stress is regarded as the major damaging phenomenon, and increasing evidence regards handling of spermatozoa - including sex sorting - as basic ground for oxidative damage. The aim of this study was to disclose whether the flow cytometric sorting procedure increases the production of reactive oxygen species (ROS), and to identify if ROS production relates to DNA damage in sorted spermatozoa using specific flow cytometry-based assays. After sorting, oxidative stress increased from 26% to 33% in pre-and post-incubation controls, to 46% after sex sorting (p < 0.05). Proportions of DNA fragmentation index post-sorting were approximately 10% higher (31.3%); an effect apparently conduced via oxidative DNA damage as revealed by the oxyDNA assay. The probable origin of this increased oxidative stress owes the removal of enough seminal plasma due to the unphysiological sperm extension, alongside a deleterious effect of high pressure on mitochondria during the sorting procedure.

  • 81.
    Banck, M
    et al.
    Hallands Hospital, Halmstad, Sweden.
    Heller, Ute
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Samuelsson, C
    Hallands Hospital, Halmstad, Sweden.
    Wickerts, CJ
    Danderyd Hospital and Karolinska Institutet, Stockholm, Sweden.
    Sjöberg, Folke
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Anaesthesiology and Intensive Care in Linköping.
    Walther, Sten
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Women with out-of-hospital cardiac arrest are less likely to receive therapeutic hypothermia and more likely to die than men: Swedish nationwide cohort study2013Conference paper (Refereed)
  • 82.
    Banck, M
    et al.
    Svenska Intensivvårdsregistret, Karlstad.
    Walther, Sten
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Karlström, G
    Svenska Intensivvårdsregistret, Karlstad.
    Nolin, T
    Svenska Intensivvårdsregistret, Kristianstad.
    Sjöberg, Folke
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Anaesthesiology and Intensive Care in Linköping.
    Samuelsson, C
    Svenska Intensivvårdsregistret, Karlstad.
    Är svensk intensivvård könsjämlik?2013Conference paper (Refereed)
  • 83.
    Banck, Malin
    et al.
    Hallands sjukhus, Halmstad.
    Walther, Sten
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Karlström, Göran
    Centralsjukhuset, Karlstad.
    Sjöberg, Folke
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Anaesthesiology and Intensive Care in Linköping.
    Samuelsson, Carolina
    Hallands sjukhus, Halmstad.
    Män intensivvårdas mer än kvinnor: Med det är ändå oklart om intensivvården i Sverige är könsojämlik2014In: Läkartidningen, ISSN 0023-7205, Vol. 111, no 9-10, 388-390 p.Article in journal (Other academic)
  • 84.
    Bang, Peter
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Polak, Michel
    University of Paris 05, France.
    Woelfle, Joachim
    University of Bonn, Germany.
    Houchard, Aude
    Ipsen Pharma, France.
    Effectiveness and Safety of rhIGF-1 Therapy in Children: The European Increlex (R) Growth Forum Database Experience2015In: Hormone Research in Paediatrics, ISSN 1663-2818, E-ISSN 1663-2826, Vol. 83, no 5, 345-357 p.Article in journal (Refereed)
    Abstract [en]

    Background/Aims: We report data from the EU Increlex (R) Growth Forum Database (IGFD) Registry, an ongoing, open-label, observational study monitoring clinical practice use of recombinant human insulin-like growth factor-1 (rhIGF-1) therapy in children. Methods: Safety and effectiveness data on rhIGF-1 treatment of 195 enrolled children with growth failure were collected from December 2008 to September 2013. Results: Mean +/- SD (95% CI) height velocity during first year of rhIGF-1 treatment was 6.9 +/- 2.2 cm/year (6.5; 7.2) (n = 144); in prepubertal patients naive to treatment, this was 7.3 +/- 2.0 cm/year (6.8; 7.7) (n = 81). Female sex, younger age at start of rhIGF-1 therapy, and lower baseline height SDS predicted first-year change in height SDS. The most frequent targeted treatment-emergent adverse events (% patients) were hypoglycemia (17.6%, predictors: young age, diagnosis of Laron syndrome, but not rhIGF-1 dose), lipohypertrophy (10.6%), tonsillar hypertrophy (7.4%), injection site reactions (6.4%), and headache (5.9%). Sixty-one serious adverse events (37 related to rhIGF-1 therapy) were reported in 31 patients (16.5%). Conclusion: Safety and effectiveness data on use of rhIGF-1 in a real-world setting were similar to those from controlled randomized trials. Severe growth phenotype and early start of rhIGF-1 improved height response and predicted risk of hypoglycemia. (C) 2015 S. Karger AG, Basel

  • 85.
    Bang, Peter
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Thorell, Anders
    Karolinska Institute, Sweden; Ersta Hospital, Sweden.
    Carlsson-Skwirut, Christine
    Karolinska Hospital and Institute, Sweden.
    Ljungqvist, Olle
    Örebro University Hospital, Sweden.
    Brismar, Kerstin
    Karolinska Hospital and Institute, Sweden.
    Nygren, Jonas
    Karolinska Institute, Sweden; Ersta Hospital, Sweden.
    Free dissociable IGF-I: Association with changes in IGFBP-3 proteolysis and insulin sensitivity after surgery2016In: Clinical Nutrition, ISSN 0261-5614, E-ISSN 1532-1983, Vol. 35, no 2, 408-413 p.Article in journal (Refereed)
    Abstract [en]

    Background: Patients receiving a carbohydrate drink (CHO) before major abdominal surgery display improved insulin sensitivity postoperatively and increased proteolysis of IGFBP-3 (IGFBP-3-PA) compared to patients undergoing similar surgery after overnight fasting. Aims: We hypothesized that serum IGFBP-3-PA increases bioavailability of circulating IGF-I and preserves insulin sensitivity in patients given CHO. Design: Matched control study. Methods: At Karolinska University Hospital, patients given CHO before major elective abdominal surgery (CHO,n = 8) were compared to patients undergoing similar surgical procedures after overnight fasting (FAST,n = 10). Results from two different techniques for determination of free-dissociable IGF-I (fdIGF-I) were compared with changes in IGFBP-3-PA and insulin sensitivity. Results: Postoperatively, CHO displayed 18% improvement in insulin sensitivity (hyperinsulinemic clamp) and increased IGFBP-3-PA vs. FAST. As determined by IRMA, fdIGF-I increased by 48 +/- 25% in CHO while fdIGF-I decreased by 13 +/- 18% in FAST (p < 0.01 vs. CHO, when corrected for duration of surgery). However, fdIGF-I determined by ultra-filtration decreased similarly in both groups (-22 +/- 8% vs. -25 +/- 8%, p = 0.8) and IGFBP-1 increased similarly in both groups. Patients with less insulin resistance after surgery demonstrated larger increases in fdIGF-I by IRMA (r = 0.58, p < 0.05). Fifty-three % of the variability of the changes in fdIGF-I by IRMA could be explained by changes in IGFBP-3-PA and total IGF-I levels (p < 0.05), while IGFBP-1 did not contribute significantly. Conclusion: During conditions when serum IGF-I bioavailability is regulated by IGFBP-3 proteolysis, measurements of fdIGF-I by IRMA is of physiological relevance as it correlates with the associated changes in insulin sensitivity. (C) 2015 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  • 86.
    Barker, A.
    et al.
    Cambridge Institute Public Heatlh, England .
    Lauria, A.
    University of Campus Biomed, Italy .
    Schloot, N.
    University of Dusseldorf, Germany University of Dusseldorf, Germany .
    Hosszufalusi, N.
    Semmelweis University, Hungary .
    Ludvigsson, Johnny
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Mathieu, C.
    Katholieke University of Leuven, Belgium .
    Mauricio, D.
    Hospital Arnau Vilanova, Spain .
    Nordwall, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Norrköping.
    Van der Schueren, B.
    Katholieke University of Leuven, Belgium .
    Mandrup-Poulsen, T.
    University of Copenhagen, Denmark .
    Scherbaum, W .A.
    University of Dusseldorf, Germany .
    Weets, I.
    Vrije University of Brussel, Belgium Vrije University of Brussel, Belgium Belgian Diabet Registry BDR, Belgium .
    Gorus, F. K.
    Vrije University of Brussel, Belgium Vrije University of Brussel, Belgium Belgian Diabet Registry BDR, Belgium .
    Wareham, N.
    Cambridge Institute Public Heatlh, England .
    Leslie, R. D.
    Queen Mary University of London, England .
    Pozzilli, P.
    University of Campus Biomed, Italy Queen Mary University of London, England .
    Age-dependent decline of beta-cell function in type 1 diabetes after diagnosis: a multi-centre longitudinal study2014In: Diabetes, obesity and metabolism, ISSN 1462-8902, E-ISSN 1463-1326, Vol. 16, no 3, 262-267 p.Article in journal (Refereed)
    Abstract [en]

    AimsC-peptide secretion is currently the only available clinical biomarker to measure residual -cell function in type 1 diabetes. However, the natural history of C-peptide decline after diagnosis can vary considerably dependent upon several variables. We investigated the shape of C-peptide decline over time from type 1 diabetes onset in relation to age at diagnosis, haemoglobin A1c (HbA1c) levels and insulin dose. MethodsWe analysed data from 3929 type 1 diabetes patients recruited from seven European centres representing all age groups at disease onset (childhood, adolescence and adulthood). The influence of the age at onset on -cell function was investigated in a longitudinal analysis at diagnosis and up to 5-years follow-up. ResultsFasting C-peptide (FCP) data at diagnosis were available in 3668 patients stratified according to age at diagnosis in four groups (less than5years, n=344; greater than5yearsless than10years, n=668; greater than10yearsless than18years, n=991; greater than18years, n=1655). FCP levels were positively correlated with age (pless than0.001); the subsequent decline in FCP over time was log-linear with a greater decline rate in younger age groups (pless than0.0001). ConclusionsThis study reveals a positive correlation between age at diagnosis of type 1 diabetes and FCP with a more rapid decline of -cell function in the very young patients. These data can inform the design of clinical trials using C-peptide values as an end-point for the effect of a given treatment.

  • 87.
    Barranco, I.
    et al.
    University of Murcia, Spain.
    Tvarijonaviciute, A.
    University of Murcia, Spain.
    Perez-Patino, C.
    University of Murcia, Spain.
    Alkmin, D. V.
    University of Murcia, Spain.
    Ceron, J. J.
    University of Murcia, Spain.
    Martinez, E. A.
    University of Murcia, Spain.
    Rodriguez-Martinez, Heriberto
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Roca, J.
    University of Murcia, Spain.
    The activity of paraoxonase type 1 (PON-1) in boar seminal plasma and its relationship with sperm quality, functionality, and in vivo fertility2015In: Andrology, ISSN 2047-2919, E-ISSN 2047-2927, Vol. 3, no 2, 315-320 p.Article in journal (Refereed)
    Abstract [en]

    Paraoxonase 1 (PON-1) is a hydrolytic enzyme present in body fluids, capable of protecting cells against oxidative stress. The hypothesis was hereby to test that PON-1, present in seminal plasma (SP), acts protecting boar spermatozoa when showing a reasonable high activity in the ejaculate. SP-PON-1 activity differed (pless than0.001) among boars (from 0.10 to 0.29IU/mL). Intra-boar variability was also observed (pless than0.05), but only in two of the 15 boars. SP-PON-1 activity differed among ejaculate portions, showing the spermatozoa-peak portion of spermatozoa-rich ejaculate fraction the highest levels (0.35 +/- 0.03IU/mL, ranging from 0.12 to 0.69) and the post-sperm ejaculate fraction the lowest levels (0.12 +/- 0.01IU/mL, ranging from 0.03 to 0.21). SP-PON-1 activity was positively correlated with the percentage of spermatozoa with rapid and progressive movement (pless than0.01) and negatively correlated with the generation of intracellular reactive oxygen species (pless than0.01) in semen samples after 72h of liquid storage. SP-PON-1 activity was highest (pless than0.01) in boars with highest farrowing rates. In conclusion, SP-PON-1 activity differed among boars and ejaculate fractions/portions. SP-PON-1 activity was positively correlated with sperm quality and functionality of liquid-stored semen samples and it evidenced a positive association with in vivo fertility.

  • 88.
    Barranco, Isabel
    et al.
    University of Murcia, Murcia, Spain.
    Perez-Patiño, Cristina
    University of Murcia, Murcia, Spain.
    Tvarijonaviciute, Asta
    University of Murcia, Murcia, Spain.
    Parrilla, Inmaculada
    University of Murcia, Murcia, Spain.
    Vicente-Carrillo, Alejandro
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Alvarez-Rodriguez, Manuel
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Ceron, Jose J
    University of Murcia, Murcia, Spain.
    Martinez, Emilio A
    University of Murcia, Murcia, Spain.
    Rodriguez-Martinez, Heriberto
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Roca, Jordi
    University of Murcia, Murcia, Spain.
    Active paraoxonase 1 is synthesised throughout the internal boar genital organs.2017In: Reproduction (Cambridge, England), ISSN 1741-7899, Vol. 154, no 3, 237-243 p.Article in journal (Refereed)
    Abstract [en]

    The paraoxonase type 1 (PON1) is an enzyme with antioxidant properties recently identified in the seminal plasma (SP) of several species, including the porcine. The aims of the present study were to (1) describe the immunohistochemical localisation of PON1 in the genital organs of fertile boars and (2) evaluate the relationship among PON1 activity and high-density lipoprotein cholesterol (HDL-C) concentration in fluids of the boar genital organs. Immunohistochemical analysis demonstrated that PON1 was present in testis (specifically in Leydig cells, blood vessels, spermatogonia and elongated spermatids), epididymis (specifically in the cytoplasm of the principal epithelial cells, luminal secretion and in the surrounding smooth muscle) and the lining epithelia of the accessory sexual glands (cytoplasmic location in the prostate and membranous in the seminal vesicle and bulbourethral glands). The Western blotting analysis confirmed the presence of PON1 in all boar genital organs, showing in all of them a band of 51 kDa and an extra band of 45 kDa only in seminal vesicles. PON1 showed higher activity levels in epididymal fluid than those in SP of the entire ejaculate or of specific ejaculate portions. A highly positive relationship between PON1 activity and HDL-C concentration was found in all genital fluids. In sum, all boar genital organs contributing to sperm-accompanying fluid/s were able to express PON1, whose activity in these genital fluids is highly dependent on the variable HDL-C concentration present.

    The full text will be freely available from 2018-06-12 17:07
  • 89.
    Barranco, Isabel
    et al.
    University of Murcia, Spain.
    Roca, Jordi
    University of Murcia, Spain.
    Tvarijonaviciute, Asta
    University of Murcia, Spain.
    Rubér, Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Vicente Carrillo, Alejandro
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Atikuzzaman, Mohammad
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Ceron, Jose J.
    University of Murcia, Spain.
    Martinez, Emilio A.
    University of Murcia, Spain.
    Rodriguez-Martinez, Heriberto
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Measurement of Activity and Concentration of Paraoxonase 1 (PON-1) in Seminal Plasma and Identification of PON-2 in the Sperm of Boar Ejaculates2015In: Molecular Reproduction and Development, ISSN 1040-452X, E-ISSN 1098-2795, Vol. 82, no 1, 58-65 p.Article in journal (Refereed)
    Abstract [en]

    This study revealed and characterised the presence of the antioxidant enzymes paraoxonase (PON) type 1 (PON-1, extracellular) and type 2 (PON-2, intracellular) in boar semen. To evaluate PON-1, an entire ejaculate from each of ten boars was collected and the seminal plasma was harvested after double centrifugation (1,500g for 10min). Seminal plasma was analysed for concentration as well as enzymatic activity of PON-1 and total cholesterol levels. Seminal-plasma PON-1 concentration ranged from 0.961 to 1.670ng/ml while its enzymatic activity ranged from 0.056 to 0.400 IU/ml, which represent individual variance. Seminal-plasma PON-1 concentration and enzymatic activity were negatively correlated (r=-0.763; Pless than0.01). The activity of seminal-plasma PON-1 negatively correlated with ejaculate volume (r=-0.726, Pless than0.05), but positively correlated with sperm concentration (r=0.654, Pless than0.05). Total seminal-plasma cholesterol concentration positively correlated with PON-1 activity (r=0.773; Pless than0.01), but negatively correlated with PON-1 concentration (r=-0.709; Pless than0.05). The presence of intracellular PON-2 was determined via immunocytochemistry in spermatozoa derived from artificial insemination. PON-2 localised to the post-acrosomal area of the sperm head and principal piece of the tail in membrane-intact spermatozoa. In summary, PON is present in boar semen, with PON-1 at low levels in seminal plasma and PON-2 within the spermatozoa. Further studies are needed to characterise the relationship between antioxidant PONs with sperm and other seminal-plasma parameters. Mol. Reprod. Dev. 82: 58-65, 2015. (c) 2014 Wiley Periodicals, Inc.

  • 90.
    Barranco, Isabel
    et al.
    University of Murcia, Spain.
    Rubér, Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Perez-Patino, Cristina
    University of Murcia, Spain.
    Atikuzzaman, Mohammad
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Martinez, Emilio A.
    University of Murcia, Spain.
    Roca, Jordi
    University of Murcia, Spain.
    Rodriguez-Martinez, Heriberto
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    The Seminal Plasma of the Boar is Rich in Cytokines, with Significant Individual and Intra-Ejaculate Variation2015In: American Journal of Reproductive Immunology, ISSN 1046-7408, E-ISSN 1600-0897, Vol. 74, no 6, 523-532 p.Article in journal (Refereed)
    Abstract [en]

    Problem The boar, as human, sequentially ejaculates sperm-rich and sperm-poor fractions. Seminal plasma (SP) spermadhesins (PSP-I/PSP-II) induce a primary endometrial inflammatory response in female sows, similar to that elicited by semen deposition in other species, including human. However, the SP is also known to mitigate such response, making it transient to allow for embryo entry to a cleansed endometrium. Although cytokine involvement has been claimed, the exploration of cytokines in different SP fractions is scarce. This study determines Th1, Th2, Th17 and Th3 cytokine profiles in specific ejaculate SP fractions from boars of proven fertility. Methods SP samples from the sperm-rich fraction (SRF) and the sperm-poor post-SRF fraction (post-SRF) of manually collected ejaculates from eight boars (four ejaculates per boar) were analysed by commercial multiplex bead assay kits (Milliplex MAP, Millipore, USA) for interferon-gamma, interferon gamma-induced protein 10, macrophage-derived chemokine, growth-regulated oncogene, granulocyte-macrophage colony-stimulating factor, monocyte chemo-attractant protein-1, interleukins (IL)-6, IL-8, IL-10, IL-15, IL-17 and transforming growth factor (TGF)-beta 1-beta 3. Results Cytokine concentrations differed between the ejaculate fractions among boars, being highest in the post-SRF. Conclusion Boar SP is rich in Th1, Th2, Th17 and Th3 cytokines, with lowest concentrations in the sperm-peak-containing fraction, indicating its main immune influence might reside in the larger, protein-rich sperm-poor post-SRF.

  • 91.
    Barranco, Isabel
    et al.
    University of Murcia, Spain.
    Tvarijonaviciute, Asta
    University of Murcia, Spain.
    Perez-Patino, Cristina
    University of Murcia, Spain.
    Parrilla, Inmaculada
    University of Murcia, Spain.
    Ceron, Jose J.
    University of Murcia, Spain.
    Martinez, Emilio A.
    University of Murcia, Spain.
    Rodriguez-Martinez, Heriberto
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Roca, Jordi
    University of Murcia, Spain.
    High total antioxidant capacity of the porcine seminal plasma (SP-TAC) relates to sperm survival and fertility2015In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 5, no 18538Article in journal (Refereed)
    Abstract [en]

    The study attempted to clarify the role of total antioxidant capacity of seminal plasma (SP-TAC) on boar sperm survival and fertility after artificial insemination (AI). SP-TAC differed (P < 0.001) among boars (no = 15) and, to a lesser degree, among ejaculates within male (4 ejaculates/boar). SP-TAC also differed (P < 0.001) among ejaculate fractions (43 ejaculates and 3 fractions per ejaculate), of which the sperm-peak portion of the sperm rich ejaculate fraction (SRF) had the highest SP-TAC. SP-TAC was not correlated with sperm quality (motility and viability) or functionality (intracellular ROS generation and lipid peroxidation) of liquid AI-semen samples stored at 17 degrees C for 72 h (90 AI-samples), but the decline in sperm quality was larger (P < 0.05) in ejaculates with low, compared with high SP-TAC (hierarchically grouped). The SP-TAC differences among ejaculate portions agree with sperm cryosurvival rates (14 ejaculates from 7 boars), showing sperm from sperm-peak portion better (P < 0.01) post-thaw quality and functionality than those from the entire ejaculate (mainly post-SRF). Boars (no = 18) with high SP-TAC (hierarchically grouped) had higher (P < 0.05) fertility outcomes (5,546 AI-sows) than those with low SP-TAC. Measurement of SP-TAC ought to be a discriminative tool to prognosis fertility in breeding boars.

  • 92.
    Barranco, Isabel
    et al.
    University of Murcia, Spain.
    Tvarijonaviciute, Asta
    University of Murcia, Spain.
    Perez-Patino, Cristina
    University of Murcia, Spain.
    Vicente Carrillo, Alejandro
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Parrilla, Inmaculada
    University of Murcia, Spain.
    Ceron, Jose J.
    University of Murcia, Spain.
    Martinez, Emilio A.
    University of Murcia, Spain.
    Rodriguez-Martinez, Heriberto
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Roca, Jordi
    University of Murcia, Spain.
    Glutathione Peroxidase 5 Is Expressed by the Entire Pig Male Genital Tract and Once in the Seminal Plasma Contributes to Sperm Survival and In Vivo Fertility2016In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 9, e0162958Article in journal (Refereed)
    Abstract [en]

    Glutathione peroxidase-5 (GPX5) is an H2O2-scavenging enzyme identified in boar seminal plasma (SP). This study attempted to clarify its origin and role on sperm survival and fertility after artificial insemination (AI). GPX5 was expressed (Western blot and immunocytochemistry using a rabbit primary polyclonal antibody) in testes, epididymis and accessory sex glands (6 boars). SP-GPX5 concentration differed among boars (11 boars, P amp;lt; 0.001), among ejaculates within boar (44 ejaculates, P amp;lt; 0.001) and among portions within ejaculate (15 ejaculates). The first 10 mL of the spermrich fraction (SRF, sperm-peak portion) had a significantly lower concentration (8.87 +/- 0.78 ng/mL) than the rest of the SRF and the post-SRF (11.66 +/- 0.79 and 12.37 +/- 0.79 ng/mL, respectively, P amp;lt; 0.005). Spermmotility of liquid-stored semen AI-doses (n = 44, at 15-17 degrees C during 72h) declined faster in AI-doses with low concentrations of SP-GPX5 compared to those with high-levels. Boars (n = 11) with high SP-GPX5 showed higher farrowing rates and litter sizes than those with low SP-GPX5 (a total of 5,275 inseminated sows). In sum, GPX5 is widely expressed in the boar genital tract and its variable presence in SP shows a positive relationship with sperm quality and fertility outcomes of liquid-stored semen AI-doses.

  • 93.
    Barsegård Gustavsson, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Familjeterapi inom primärvården. Intervjuer med nio remittenter.2014Independent thesis Advanced level (professional degree), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    It is natural for families and couples who have problems to apply to instances other than in primary care, hence the interest to conduct a study in primary care where the purpose was to examine the problems, opportunities, and increase understanding of working with family therapy. The actual study is based on an interview study in which nine individuals with different professions were asked semi-structured questions, where their reflections and assessments, when remitted to family therapy were laying foundation for the study content. The results indicate that it is possible to work with the family system in a health center.

    The conclusion: it is possible to broaden the perspective on various therapies, as well as the opportunities to implement family therapy as a method or expand thinking about the family system when patients with mental illness find their way to a medical center.

  • 94.
    Beam, Craig A.
    et al.
    Western Michigan University, MI 49008 USA.
    MacCallum, Colleen
    Western Michigan University, MI 49008 USA.
    Herold, Kevan C.
    Yale University, CT USA; Yale University, CT USA.
    Wherrett, Diane K.
    Hospital Sick Children, Canada; University of Toronto, Canada.
    Palmer, Jerry
    University of Washington, WA 98195 USA; VA Puget Sound Health Care Syst, WA USA.
    Ludvigsson, Johnny
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    GAD vaccine reduces insulin loss in recently diagnosed type 1 diabetes: findings from a Bayesian meta-analysis2017In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 60, no 1, 43-49 p.Article in journal (Refereed)
    Abstract [en]

    GAD is a major target of the autoimmune response that occurs in type 1 diabetes mellitus. Randomised controlled clinical trials of a GAD + alum vaccine in human participants have so far given conflicting results. In this study, we sought to see whether a clearer answer to the question of whether GAD65 has an effect on C-peptide could be reached by combining individual-level data from the randomised controlled trials using Bayesian meta-analysis to estimate the probability of a positive biological effect (a reduction in C-peptide loss compared with placebo approximately 1 year after the GAD vaccine). We estimate that there is a 98% probability that 20 mu g GAD with alum administered twice yields a positive biological effect. The effect is probably a 15-20% reduction in the loss of C-peptide at approximately 1 year after treatment. This translates to an annual expected loss of between -0.250 and -0.235 pmol/ml in treated patients compared with an expected 2 h AUC loss of -0.294 pmol/ml at 1 year for untreated newly diagnosed patients. The biological effect of this vaccination should be developed further in order to reach clinically desirable reductions in insulin loss in patients recently diagnosed with type 1 diabetes.

  • 95.
    Bengtsson, Kristofer
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Jonson, Carl-Oscar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Disaster Medicine and Traumatology.
    Prytz, Erik G.
    Linköping University, Department of Computer and Information Science, Human-Centered systems. Linköping University, Faculty of Arts and Sciences.
    Framtidens skadeplats: intervjuer med landstingens beredskapssamordnare2016Report (Other academic)
    Abstract [sv]

    Syftet med föreliggande studie var att genom intervjuer med beredskapssamordnare från Sveriges landsting försöka skapa en bild av hur uppfattningen var att skadeplatsen såg ut idag och skulle kunna kommat att förändras på sikt. Vidare önskade intervjustudien söka svar på frågor som rörde komplexiteten på skadeplatsen genom att diskutera ledningsförhållanden, samverkan med andra aktörer, alarmerings- och dirigeringsfunktionernas roll i det svenska sjukvårdsystemet samt hur ett möjligt arbete med ett återtagande av förmågan till ett civilt försvar skulle påverka systemet i sin helhet. Överlag har detta syfte uppnåtts genom ett rikt material kring relevanta frågeställningar som belyst ett flertal kritiska aspekter både i dagens situation men även för framtiden.

    Resultatet ger en relativt entydig bild av hur situationen uppfattas på landstingsnivå idag av personalen som behandlar beredskapsfrågorna. Den bild som målas upp fokuserar kanske främst på en upplevd avsaknad av centrala och nationellt övergripande styrningar vilket menligt påverkar förmågan att lyfta ledningsförmågan från regional till nationell nivå vid en större händelse som överstiger den regionala förmågan. Den svenska modellen för att hantera samhällsstörningar av idag är väl anpassad för att hantera händelser inom ramen för det egna länets geografiska område. Befintliga koncept för samverkan och samordning bedöms fungera bra i vardagen, exempelvis vid de vanligaste fallen av skadeplatser: trafik och brand. Detta innebär dock att systemet fungerar väl under förutsättning att händelsen är begränsad i såväl tid och rum som vad avser antalet drabbade. En större händelse eller flera händelser samtidigt på olika platser, särskilt om det finns försvårande faktorer såsom utsläpp av farliga ämnen eller en högre hotbild, skapar försvårande omständigheter som upplevs svårhanterliga idag. I ett framtida scenario upplevs även risken för dessa händelser och terrorattacker att öka. Avhängigheten av IT samt ett samhälle som i allt högre grad förlitar sig på ”just in time”-leveranser gör att sårbarheten har ökat och upplevs fortsätta göra det även i framtiden. Andra viktiga områden som lyfts är nuvarande och befarad framtida brist på kompetent personal samt att utbildnings- och övningsverksamhet inte kan bedrivas i önskvärd utsträckning, delvis på grund av personalbrist och –omsättning.

    Vidare syns den generella uppfattningen vara att det saknas ett tydligt ledarskap på nationell nivå då det sällan, om alls, utkommer några direkta styrningar rörande vad som skall uppnås och i vilken utsträckning. Detta har också påvisats i avsnittet ovan rörande före-, under- och efterperspektivet där det finns en klart övervägande del synpunkter på de två förstnämnda perspektiven. Nationell styrning är alltså något som uppfattas vara efterfrågat och då inte bara avseende ledning under insats utan även i frågor rörande enhetlig utrustning och metodik samt utbildnings- och övningsfrågor. Få respondenter har tagit upp efterperspektivet i någon större utsträckning men då det har förekommit har det framförallt berört erfarenhetshanteringsfrågor och den brist som upplevs finnas inom detta specifika område idag. Erfarenheter från den egna verksamheten, såväl i vardagen som vid insatser vid allvarliga händelser, behöver tas om hand, följas upp och sedan utgöra grund för ett levande utvecklingsarbete.

  • 96.
    Benson, Mikael
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Allergy Center.
    Clinical implications of omics and systems medicine: focus on predictive and individualized treatment2016In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 279, no 3, 229-240 p.Article, review/survey (Refereed)
    Abstract [en]

    Many patients with common diseases do not respond to treatment. This is a key challenge to modern health care, which causes both suffering and enormous costs. One important reason for the lack of treatment response is that common diseases are associated with altered interactions between thousands of genes, in combinations that differ between subgroups of patients who do or do not respond to a given treatment. Such subgroups, or even distinct disease entities, have been described recently in asthma, diabetes, autoimmune diseases and cancer. High-throughput techniques (omics) allow identification and characterization of such subgroups or entities. This may have important clinical implications, such as identification of diagnostic markers for individualized medicine, as well as new therapeutic targets for patients who do not respond to existing drugs. For example, whole-genome sequencing may be applied to more accurately guide treatment of neurodevelopmental diseases, or to identify drugs specifically targeting mutated genes in cancer. A study published in 2015 showed that 28% of hepatocellular carcinomas contained mutated genes that potentially could be targeted by drugs already approved by the US Food and Drug Administration. A translational study, which is described in detail, showed how combined omics, computational, functional and clinical studies could identify and validate a novel diagnostic and therapeutic candidate gene in allergy. Another important clinical implication is the identification of potential diagnostic markers and therapeutic targets for predictive and preventative medicine. By combining computational and experimental methods, early disease regulators may be identified and potentially used to predict and treat disease before it becomes symptomatic. Systems medicine is an emerging discipline, which may contribute to such developments through combining omics with computational, functional and clinical studies. The aims of this review are to provide a brief introduction to systems medicine and discuss how it may contribute to the clinical implementation of individualized treatment, using clinically relevant examples.

  • 97.
    Beraki, Å
    et al.
    Linköping University.
    Magnuson, A.
    Örebro University Hospital, Sweden .
    Särnblad, S.
    Örebro University Hospital, Sweden; Örebro University, Sweden.
    Åman, J.
    Örebro University Hospital, Sweden; Örebro University, Sweden.
    Samuelsson, Ulf
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Increase in physical activity is associated with lower HbA1c levels in children and adolescents with type 1 diabetes: results from a cross-sectional study based on the Swedish pediatric diabetes quality registry (SWEDIABKIDS)2014In: Diabetes Research and Clinical Practice, ISSN 0168-8227, E-ISSN 1872-8227, Vol. 105, no 1, 119-125 p.Article in journal (Refereed)
    Abstract [en]

    AIMS:

    To evaluate the associations between physical activity (PA) and metabolic control, measured by glycated hemoglobin (HbA1c), in a large group of children and adolescents with type 1 diabetes.

    METHODS:

    Cross-sectional analysis of data from 4655 patients, comparing HbA1c values with levels of physical activity. The data for the children and adolescents were obtained from the Swedish pediatric diabetes quality registry, SWEDIABKIDS. The patients were 7-18 years of age, had type 1 diabetes and were not in remission. Patients were grouped into five groups by frequency of PA.

    RESULTS:

    Mean HbA1c level was higher in the least physically active groups (PA0: 8.8% ± 1.5 (72 ± 16 mmol/mol)) than in the most physically active groups (PA4: 7.7% ± 1.0 (60 ± 11 mmol/mol)) (p<0.001). An inverse dose-response association was found between PA and HbA1c (β: -0.30, 95% CI: -0.34 to -0.26, p<0.001). This association was found in both sexes and all age groups, apart from girls aged 7-10 years. Multiple regression analysis revealed that the relationship remained significant (β: -0.21, 95% CI: -0.25 to -0.18, p<0.001) when adjusted for possible confounding factors.

    CONCLUSIONS:

    Physical activity seems to influence HbA1c levels in children and adolescents with type 1 diabetes. In clinical practice these patients should be recommended daily physical activity as a part of their treatment.

  • 98.
    Bergfelt, Emma
    et al.
    Uppsala University, Sweden.
    Kozlowski, Piotr
    University of Örebro, Sweden.
    Ahlberg, Lucia
    Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Haematology. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences.
    Hulegardh, Erik
    Sahlgrens University Hospital, Sweden.
    Hagglund, Hans
    Karolinska Institute, Sweden.
    Karlsson, Karin
    Skåne University Hospital, Sweden.
    Markuszewska-Kuczymska, Alicja
    University of Umeå Hospital, Sweden.
    Tomaszewska-Toporska, Beata
    Skåne University Hospital, Sweden.
    Smedmyr, Bengt
    Uppsala University, Sweden.
    Astrom, Maria
    University of Örebro, Sweden.
    Amini, Rose-Marie
    Uppsala University, Sweden.
    Hallbook, Helene
    Uppsala University, Sweden.
    Satisfactory outcome after intensive chemotherapy with pragmatic use of minimal residual disease (MRD) monitoring in older patients with Philadelphia-negative B cell precursor acute lymphoblastic leukaemia: a Swedish registry-based study2015In: Medical Oncology, ISSN 1357-0560, E-ISSN 1559-131X, Vol. 32, no 4, 135- p.Article in journal (Refereed)
    Abstract [en]

    The introduction of minimal residual disease (MRD) monitoring, in the Swedish national guidelines for acute lymphoblastic leukaemia, was evaluated in 35 patients aged 46-79 years (median 61), who were diagnosed from 2007 to 2011 and treated with high-intensity, block-based chemotherapy (ABCDV/VABA induction). Both a high complete remission rate (91 %) and acceptable overall survival (OS) rate (47 %) at 5 years were achieved. MRD by flow cytometry was measured in 73 % of the patients reaching complete remission after the first course, but was omitted by the clinicians for eight patients who were either over 70 years of age or already met conventional high-risk criteria. Factors negatively influencing OS were age over 65 years and WHO status greater than= 2. MRD less than 0.1 % after induction had positive impact on continuous complete remission but not on OS. Only five patients were allocated to allogeneic haematopoietic stem cell transplantation in first remission, mainly due to conventional high risk factors. Thus, use of intensive remission induction therapy is effective in a selection of older patients. In a population for whom the possibilities of treatment escalation are limited, the optimal role of MRD monitoring remains to be determined.

  • 99.
    Bergfors, Elisabet
    et al.
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in West Östergötland, Research & Development Unit in Local Health Care. University of Gothenburg, Sweden.
    Hermansson, Göran
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Nyström Kronander, Ulla
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Allergy Center.
    Falk, Lars
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in West Östergötland, Research & Development Unit in Local Health Care. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Dermatology and Venerology.
    Valter, Lars
    Östergötlands Läns Landsting, Local Health Care Services in West Östergötland, Research & Development Unit in Local Health Care.
    Trollfors, Birger
    Sahlgrenska University Hospital-East, Gothenburg, Sweden .
    How common are long-lasting, intensely itching vaccination granulomas and contact allergy to aluminium induced by currently used pediatric vaccines? A prospective cohort study2014In: European Journal of Pediatrics, ISSN 0340-6199, E-ISSN 1432-1076, Vol. 173, no 10, 1297-1307 p.Article in journal (Refereed)
    Abstract [en]

    The frequency of long-lasting, intensely itching subcutaneous nodules at the injection site for aluminium (Al)-adsorbed vaccines (vaccination granulomas) was investigated in a prospective cohort study comprising 4,758 children who received either a diphtheria-tetanus-pertussis-polio-Haemophilus influenzae type b vaccine (Infanrix®, Pentavac®) alone or concomitant with a pneumococcal conjugate (Prevenar). Both vaccines were adsorbed to an Al adjuvant. Altogether 38 children (0.83 %) with itching granulomas were identified, epicutaneously tested for Al sensitisation and followed yearly. Contact allergy to Al was verified in 85 %. The median duration of symptoms was 22 months in those hitherto recovered. The frequency of granulomas induced by Infanrix® was >0.66 % and by Prevenar >0.35 %. The risk for granulomas increased from 0.63 to 1.18 % when a second Al-adsorbed vaccine was added to the schedule. Conclusion: Long-lasting itching vaccination granulomas are poorly understood but more frequent than previously known after infant vaccination with commonly used diphtheria-tetanus-pertussis-polio-Haemophilus influenzae type b and pneumococcal conjugate vaccines. The risk increases with the number of vaccines given. Most children with itching granulomas become contact allergic to aluminium. Itching vaccination granulomas are benign but may be troublesome and should be recognised early in primary health care to avoid unnecessary investigations, anxiety and mistrust.

  • 100.
    Bergh, Ann-Charlotte
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences.
    Evaldsson, Chamilly
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Chemistry.
    Pedersen, Lone Bredo
    Rigshospitalet Copenhagen, Denmark.
    Geisler, Christian
    Rigshospitalet Copenhagen, Denmark.
    Stamatopoulos, Kostas
    G. Papanicolaou Hospital, Greece.
    Rosenquist, Richard
    Rudbeck Laboratory, Uppsala University, Sweden .
    Rosén, Anders
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences.
    Silenced B-cell receptor response to autoantigen in a poor-prognostic subset of chronic lymphocytic leukemia2014In: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 99, no 11, 1722-1730 p.Article in journal (Refereed)
    Abstract [en]

    Chronic lymphocytic leukemia B-cells express auto/xeno-antigen-reactive antibodies that bind to self-epitopes and resemble natural IgM antibodies in their repertoire. One of the antigenic structures recognized is oxidation-induced malonedialdehyde present on low-density lipoprotein, apoptotic blebs, and on certain microbes. The poor-prognostic stereotyped subset #1 (Clan I IGHV genes-IGKV1(D)-39) express IgM B-cell receptors that bind oxidized low-density lipoprotein. In this study, we have used for the first time this authentic cognate antigen, since it is more faithful to B-cell physiology than anti-IgM, for analysis of downstream B-cell receptor-signal transduction events. Multivalent oxidized low-density lipoprotein showed specific binding to subset #1 IgM/IgD B-cell receptors, whereas native low-density lipoprotein did not. The antigen-binding induced prompt receptor-clustering, followed by internalization. However, the receptor-signal transduction was silenced, revealing no Ca2+ mobilization or cell-cycle entry, while phosphorylated extracellular-regulated kinase1/2 basal levels were high and could not be elevated further by oxidized low-density lipoprotein. Interestingly, B-cell receptor responsiveness was recovered after 48 hours culture in the absence of antigen in half of the cases. Toll-like receptor 9-ligand was found to breach the B-cell receptor-signaling incompetence in 5 of 12 cases pointing to intra-subset heterogeneity. Altogether, this study supports B-cell receptor-unresponsiveness to cognate self-antigen on its own in poor-prognostic subset #1 chronic lymphocytic leukemia indicating that these cells proliferate by other mechanisms that may override B-cell receptor-silencing brought about in a context of self-tolerance/anergy. These novel findings have implications for the understanding of chronic lymphocytic leukemia pathobiology and therapy.

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