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  • 251.
    Alvaeus, Julia
    et al.
    Umea Univ, Sweden.
    Rosenblatt, Robert
    Umea Univ, Sweden; Stockholm South Gen Hosp, Sweden.
    Johansson, Markus
    Umea Univ, Sweden; Sundsvall Hosp, Sweden.
    Alamdari, Farhood
    Vastmanland Hosp, Sweden.
    Jakubczyk, Tomasz
    Lanssjukhuset Ryhov, Sweden.
    Holmstrom, Benny
    Uppsala Univ, Sweden.
    Hemdan, Tammer
    Uppsala Univ, Sweden.
    Huge, Ylva
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland.
    Abdul-Sattar Aljabery, Firas
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland.
    Gabrielsson, Susanne
    Karolinska Inst, Sweden.
    Riklund, Katrine
    Umea Univ, Sweden.
    Winqvist, Ola
    Karolinska Univ Hosp, Sweden.
    Sherif, Amir
    Umea Univ, Sweden.
    Fewer tumour draining sentinel nodes in patients with progressing muscle invasive bladder cancer, after neoadjuvant chemotherapy and radical cystectomy2019In: World journal of urology, ISSN 0724-4983, E-ISSN 1433-8726Article in journal (Refereed)
    Abstract [en]

    Purpose To examine the relationship between the number of tumour draining sentinel nodes (SNs) and pathoanatomical outcomes, in muscle-invasive bladder cancer (MIBC), in patients undergoing neoadjuvant chemotherapy (NAC) and radical cystectomy (RC). Materials and Methods In an ongoing prospective multicenter study, we included 230 patients with suspected urothelial MIBC from ten Swedish urological centers. All underwent TURb and clinical staging. From the cohort, 116 patients with urothelial MIBC; cT2-cT4aN0M0, underwent radical cystectomy (RC) and lymphadenectomy with SN-detection (SNd). 83 patients received cisplatin-based NAC and 33 were NAC-naive. The number and locations of detected SNs and non-SNs were recorded for each patient. The NAC treated patients were categorized by pathoanatomical outcomes post-RC into three groups: complete responders (CR), stable disease (SD) and progressive disease (PD). Selected covariates with possible impact on SN-yield were tested in uni -and multivariate analyses for NAC-treated patients only. Results In NAC treated patients, the mean number of SNs was significantly higher in CR patients (3.3) and SD patients (3.6) compared with PD patients (1.4) (p = 0.034). In a linear multivariate regression model, the number of harvested nodes was the only independent variable that affected the number of SNs (p = 0.0004). Conclusions The number of tumor-draining SNs in NAC-treated patients was significantly lower in patients with progressive disease.

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  • 252.
    Alvarez-Rodriguez, Manuel
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Univ Autonoma Barcelona, Spain.
    Alvarez, M.
    Univ Leon, Spain.
    Anel-Lopez, L.
    Univ Leon, Spain.
    Guerra, C.
    Univ Leon, Spain.
    Chamorro, C. A.
    Univ Leon, Spain.
    Anel, L.
    Univ Leon, Spain.
    de Paz, P.
    Univ Leon, Spain.
    Martinez-Pastor, F.
    Univ Leon, Spain.
    Effect of length of time post-mortem on quality and freezing capacity of Cantabric chamois (Rupicapra pyrenaica parva) epididymal spermatozoa2018In: Animal Reproduction Science, ISSN 0378-4320, E-ISSN 1873-2232, Vol. 198, p. 184-192Article in journal (Refereed)
    Abstract [en]

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

  • 253.
    Alvarez-Rodriguez, Manuel
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Alvarez, M.
    University of Leon, Spain.
    Anel-Lopez, L.
    SaBio IREC CSIC UCLM JCCM, Spain.
    Lopez-Uruena, E.
    University of Leon, Spain.
    Manrique, P.
    University of Leon, Spain.
    Borragan, S.
    Cabarceno Pk, Spain.
    Morrell, J. M.
    Swedish University of Agriculture Science SLU, Sweden.
    de Paz, P.
    University of Leon, Spain.
    Anel, L.
    University of Leon, Spain.
    Effect of colloid (Androcoll-Bear, Percoll, and PureSperm) selection on the freezability of brown bear (Ursus arctos) sperm2016In: Theriogenology, ISSN 0093-691X, E-ISSN 1879-3231, Vol. 85, no 6, p. 1097-1105Article in journal (Refereed)
    Abstract [en]

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

  • 254.
    Alvarez-Rodriguez, Manuel
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Atikuzzaman, Mohammad
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Department of Surgery and Theriogenology, Faculty of Veterinary Animal and Biomedical Sciences, Sylhet Agricultural University, Sylhet, Bangladesh.
    Venhoranta, Heli
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. University of Helsinki, Department of Production Animal Medicine, Faculty of Veterinary Medicine, Saari, Finland.
    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.
    Expression of Immune Regulatory Genes in the Porcine Internal Genital Tract Is Differentially Triggered by Spermatozoa and Seminal Plasma2019In: International Journal of Molecular Sciences, ISSN 1422-0067, E-ISSN 1422-0067, Vol. 20, no 3, article id 513Article in journal (Refereed)
    Abstract [en]

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

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  • 255.
    Alvarez-Rodriguez, Manuel
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Ljunggren, Stefan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    Karlsson, Helen
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    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.
    Exosomes in specific fractions of the boar ejaculate contain CD44: A marker for epididymosomes?2019In: Theriogenology, ISSN 0093-691X, E-ISSN 1879-3231, Vol. 140, p. 143-152Article in journal (Refereed)
    Abstract [en]

    Seminal plasma (SP) is a complex fluid containing proteins, peptides, enzymes, hormones as well as extracellular vesicles (EVs). The SP interacts with spermatozoa and the inner cell lining of the female genital tract, adsorbing proteins and exosomes that modulate sperm functions and female immune responsiveness. In the present study, boar sperm-free SP was studied using flow cytometry (FC) after membrane tetraspanins (CD9, CD63 and CD81) and membrane receptor CD44 marking of non-enriched (whole SP) or gradient fractions enriched through two-step discontinuous KBr-density-gradient ultracentrifugation, in whole ejaculate or in selected ejaculate fractions. The results, evaluated by transmission electron microscopy, confirmed the presence of exosomes in all fractions of the pig SP. Noteworthy, these pig SP-exosomes were CD44-bearing when analysed by FC, with bands detected by western blotting (WB) at the expected 85 kD size. The two-step discontinuous KBr-density-gradient ultracentrifugation enriched the population of exosomes in two specific gradient fractions, indicating exosomes (either prostasomes or epididymosomes) could be separated from low-density lipoprotein (LDL) but they co-sediment with the high-density lipoprotein (HDL)-bearing fraction. The findings pave for the selective isolation of exosomes in functional studies of their function when interacting with spermatozoa, the oocyte and/or the female genitalia, including hyaluronan-CD44 interplay. (C) 2019 Elsevier Inc. All rights reserved.

    The full text will be freely available from 2020-08-21 10:23
  • 256.
    Alvarez-Rodriguez, Manuel
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Univ Autonoma Barcelona, Spain.
    Lopez-Bejar, Manel
    Univ Autonoma Barcelona, 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.
    The risk of using monoclonal or polyclonal commercial antibodies: controversial results on porcine sperm CD44 receptor identification2019In: Reproduction in domestic animals, ISSN 0936-6768, E-ISSN 1439-0531, Vol. 54, no 4, p. 733-737Article in journal (Refereed)
    Abstract [en]

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

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  • 257.
    Alvarez-Rodriguez, Manuel
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences.
    Martinez-Serrano, Cristina
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences.
    Wright, Dominic
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Barranco, Isabel
    Univ Girona, Spain.
    Roca, Jordi
    Univ Murcia, Spain.
    Rodriguez-Martinez, Heriberto
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences.
    The Transcriptome of Pig Spermatozoa, and Its Role in Fertility2020In: International Journal of Molecular Sciences, ISSN 1422-0067, E-ISSN 1422-0067, INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, Vol. 21, no 5, article id 1572Article in journal (Refereed)
    Abstract [en]

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

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  • 258.
    Alvarez-Rodriguez, Manuel
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences.
    Ntzouni, Maria
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Wright, Dominic
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Khan, Kabirul Islam
    Chattogram Vet and Anim Sci Univ, Bangladesh.
    Lopez-Bejar, Manel
    Univ Autonoma Barcelona, Spain.
    Martinez-Serrano, Cristina
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences.
    Rodriguez-Martinez, Heriberto
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences.
    Chicken seminal fluid lacks CD9-and CD44-bearing extracellular vesicles2020In: Reproduction in domestic animals, ISSN 0936-6768, E-ISSN 1439-0531Article in journal (Refereed)
    Abstract [en]

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

  • 259.
    Alvarez-Rodriguez, Manuel
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Vicente Carrillo, Alejandro
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Evidensia Valla Djursjukhus Linkoping, Linkoping, Sweden.
    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.
    Hyaluronan improves neither the long-term storage nor the cryosurvival of liquid-stored CD44-bearing Al boar spermatozoa2018In: Journal of reproduction and development, ISSN 0916-8818, E-ISSN 1348-4400, Vol. 64, no 4, p. 351-360Article in journal (Refereed)
    Abstract [en]

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

  • 260.
    Alvarez-Rodriguez, Manuel
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Vicente-Carrillo, Alejandro
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    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.
    Exogenous Individual Lecithin-Phospholipids (Phosphatidylcholine and Phosphatidylglycerol) Cannot Prevent the Oxidative Stress Imposed by Cryopreservation of Boar Sperm.2017In: Journal of veterinary medicine and surgery, ISSN 2574-2868, Vol. 1, no 1Article in journal (Refereed)
    Abstract [en]

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

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

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

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

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

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  • 261.
    Alvarsson, Michael
    et al.
    Institutionen för molekylär medicin och kirurgi, Karolinska institutet - PO Endokrinologi och njurmedicin Stockholm, Sweden Institutionen för molekylär medicin och kirurgi, Karolinska institutet - PO Endokrinologi och njurmedicin Stockholm, Sweden.
    Östgren, Carl Johan
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Primary Care Center, Primary Health Care Center Ödeshög.
    Ny era inom terapin för typ 2-diabetes – men vad är nytt?: Metformin fortfarande förstahandsval, men därefter rekommenderas att behandlingen individualiseras2018In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 115Article in journal (Refereed)
    Abstract [en]

    n/a

  • 262.
    Alwin, Jenny
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Health Care Analysis. Linköping University, Faculty of Medicine and Health Sciences.
    Karlson, Bjorn W.
    Univ Gothenburg, Sweden; NU NAL Uddevalla Hosp Grp, Sweden.
    Husberg, Magnus
    Linköping University, Department of Medical and Health Sciences, Division of Health Care Analysis. Linköping University, Faculty of Medicine and Health Sciences.
    Carlsson, Per
    Linköping University, Department of Medical and Health Sciences, Division of Health Care Analysis. Linköping University, Faculty of Medicine and Health Sciences.
    Ekerstad, Niklas
    NU NAL Uddevalla Hosp Grp, Sweden.
    Societal costs of informal care of community-dwelling frail elderly people2020In: Scandinavian Journal of Public Health, ISSN 1403-4948, E-ISSN 1651-1905, article id UNSP 1403494819844354Article in journal (Refereed)
    Abstract [en]

    Aims: The aims of this study are to describe informal care activities and to estimate the societal cost of informal care of community-dwelling frail elderly people in Sweden. Methods: This study was performed within the frame of the TREEE project that included 408 frail elderly patients. At index hospitalisation (baseline), primary informal caregivers of the patients were provided with a questionnaire on informal care during a period of three months. Questions concerning other (secondary) informal caregivers were also included. A rough estimate of the total cost of informal care of frail elderly people in Sweden was obtained by combining data from this study with published data and official statistics. Results: In total, 176 informal caregivers responded, and 89% had provided informal care. The informal caregivers (primary and secondary) provided care for an average of 245 hours over three months. Taking care of the home was the dominating activity. In total, the mean cost of informal care was estimated to approximately 18,000 SEK (euro1878) over three months, corresponding to an annual cost of approximately 72,000 SEK (euro7477) per frail elderly person. The total annual societal costs of informal care of community dwelling frail elderly people aged 75 years and older in Sweden was estimated to be approximately 11,000 million SEK (euro1150 million). Conclusions: The care of frail elderly people provided by informal caregivers is extensive and represents a great economic value. Although our calculations are associated with uncertainty, the size indicates that supporting informal caregivers should be a priority for society.

  • 263.
    Alwin, Jenny
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Health Care Analysis. Linköping University, Faculty of Health Sciences.
    Lundqvist, Martina
    Linköping University, Department of Medical and Health Sciences, Division of Health Care Analysis. Linköping University, Faculty of Health Sciences.
    Lundqvist, Martina
    Linköping University, Department of Medical and Health Sciences, Division of Health Care Analysis. Linköping University, Faculty of Health Sciences.
    Husberg, Magnus
    Linköping University, Department of Medical and Health Sciences, Division of Health Care Analysis. Linköping University, Faculty of Health Sciences.
    Levin, Lars-Åke
    Linköping University, Department of Medical and Health Sciences, Division of Health Care Analysis. Linköping University, Faculty of Health Sciences.
    Utvärdering av försöksverksamhet med service- och signalhundar2014Report (Other academic)
    Abstract [sv]

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

      Resultat och slutsatser

    • Service- och signalhundar minskar i genomsnitt förarnas behov av offentliga stödinsatser med 197 000 kronor (6 procent) under en tioårsperiod.
    • Livskvaliteten för personer med behov av service- och signalhundar är låg jämfört med den allmänna populationen i Sverige. Studien visar på en förbättring i livskvaliteten och välbefinnandet för förare med en certifierad hund.
    • Förarnas grad av fysisk aktivitet ökade med en certifierad hund och majoriteten av dem angav att de ökat sin tid utanför hemmet samt att de även ökat sin tid för att delta i sociala aktiviteter tack vare hunden.
    • Förarnas negativa emotionella upplevelser minskar med en certifierad hund.
    • Förarna beskriver själva den certifierade hunden som ett viktigt verktyg för ökad självständighet och trygghet.
    • Den hälsoekonomiska modellen som analyserar kostnadseffektiviteten visar att ett innehav av en certifierad hund är ett dominant alternativ jämfört med att inte ha en certifierad hund. Detta innebär att kostnaderna ur ett samhällsperspektiv under en tioårsperiod är lägre (-103 000 kronor) samtidigt som effekterna i form av vunna QALY (kvalitetsjusterade levnadsår) är högre (+0,15).
    • Finansieringsanalysen visar att förare som har certifierade hundar sparar resurser åt alla aktörer (stat, kommun och landsting) men får själva ökade utgifter på grund av hunden.
    • Studien baseras på ett lågt antal observationer (56 ekipage). Det i kombination med att det är en stor spridning i resursförbrukningen mellan ekipagen medför att det finns en statistisk osäkerhet i resultaten. Slutsatserna bedöms dock som rimliga eftersom de är samstämmiga.
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  • 264.
    Aman, Malin
    et al.
    Swedish Sch Sport and Hlth Sci, Sweden.
    Larsen, Karin
    Swedish Sch Sport and Hlth Sci, Sweden; Umea Univ, Sweden.
    Forssblad, Magnus
    Swedish Sch Sport and Hlth Sci, Sweden; Karolinska Inst, Sweden.
    Näsmark, Annica
    Swedish Sch Sport and Hlth Sci, Sweden; Capio Artro Clin, Sweden.
    Waldén, Markus
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Swedish Sch Sport and Hlth Sci, Sweden.
    Hägglund, Martin
    Linköping University, Department of Medical and Health Sciences, Division of Physiotherapy. Linköping University, Faculty of Medicine and Health Sciences. Swedish Sch Sport and Hlth Sci, Sweden.
    A Nationwide Follow-up Survey on the Effectiveness of an Implemented Neuromuscular Training Program to Reduce Acute Knee Injuries in Soccer Players2018In: The Orthopaedic Journal of Sports Medicine, ISSN 2325-9671, Vol. 6, no 12, article id 2325967118813841Article in journal (Refereed)
    Abstract [en]

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

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  • 265. Order onlineBuy this publication >>
    Amirhosseini, Mehdi
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Aseptic Loosening of Orthopedic Implants: Osteoclastogenesis Regulation and Potential Therapeutics2019Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

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

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

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

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

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

    List of papers
    1. Mechanical instability and titanium particles induce similar transcriptomic changes in a rat model for periprosthetic osteolysis and aseptic loosening
    Open this publication in new window or tab >>Mechanical instability and titanium particles induce similar transcriptomic changes in a rat model for periprosthetic osteolysis and aseptic loosening
    2017 (English)In: Bone Reports, ISSN 2352-1872, Vol. 7, p. 17-25Article in journal (Refereed) Published
    Abstract [en]

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

    Place, publisher, year, edition, pages
    Elsevier, 2017
    Keywords
    Aseptic loosening; Implant; Instability; Microarray; Wear debris
    National Category
    Cell and Molecular Biology Orthopaedics
    Identifiers
    urn:nbn:se:liu:diva-146297 (URN)10.1016/j.bonr.2017.07.003 (DOI)28795083 (PubMedID)
    Available from: 2018-04-07 Created: 2018-04-07 Last updated: 2019-03-08
    2. GSK-3 beta inhibition suppresses instability-induced osteolysis by a dual action on osteoblast and osteoclast differentiation
    Open this publication in new window or tab >>GSK-3 beta inhibition suppresses instability-induced osteolysis by a dual action on osteoblast and osteoclast differentiation
    Show others...
    2018 (English)In: Journal of Cellular Physiology, ISSN 0021-9541, E-ISSN 1097-4652, Vol. 233, no 3, p. 2398-2408Article in journal (Refereed) Published
    Abstract [en]

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

    Place, publisher, year, edition, pages
    WILEY, 2018
    Keywords
    bone implant; GSK-3 beta; mechanical instability; osteolysis; Wnt signaling
    National Category
    Pharmacology and Toxicology
    Identifiers
    urn:nbn:se:liu:diva-148660 (URN)10.1002/jcp.26111 (DOI)000433519300056 ()28731198 (PubMedID)
    Note

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

    Available from: 2018-06-18 Created: 2018-06-18 Last updated: 2019-04-08
    3. Cyclin-dependent kinase 8/19 inhibition suppresses osteoclastogenesis by downregulating RANK and promotes osteoblast mineralization and cancellous bone healing.
    Open this publication in new window or tab >>Cyclin-dependent kinase 8/19 inhibition suppresses osteoclastogenesis by downregulating RANK and promotes osteoblast mineralization and cancellous bone healing.
    Show others...
    2019 (English)In: Journal of Cellular Physiology, ISSN 0021-9541, E-ISSN 1097-4652, Vol. 234, no 9, p. 16503-16516Article in journal (Refereed) Published
    Abstract [en]

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

    Keywords
    CDK8, RANK, osteoblasts, osteoclasts
    National Category
    Cell and Molecular Biology Medicinal Chemistry
    Identifiers
    urn:nbn:se:liu:diva-154927 (URN)10.1002/jcp.28321 (DOI)000470174200186 ()30793301 (PubMedID)
    Note

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

    Available from: 2019-03-05 Created: 2019-03-05 Last updated: 2019-07-03
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    Aseptic Loosening of Orthopedic Implants: Osteoclastogenesis Regulation and Potential Therapeutics
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  • 266.
    Amirhosseini, Mehdi
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Andersson, Göran
    Division of Pathology, Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital, Huddinge, Sweden.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Fahlgren, Anna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Mechanical instability and titanium particles induce similar transcriptomic changes in a rat model for periprosthetic osteolysis and aseptic loosening2017In: Bone Reports, ISSN 2352-1872, Vol. 7, p. 17-25Article in journal (Refereed)
    Abstract [en]

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

    Download full text (pdf)
    fulltext
  • 267.
    Amirhosseini, Mehdi
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Bernhardsson, Magnus
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Lång, Pernilla
    Department of Laboratory Medicine, Division of Pathology, Karolinska Institutet, Karolinska University Hospital, Huddinge, Sweden.
    Andersson, Göran
    Department of Laboratory Medicine, Division of Pathology, Karolinska Institutet, Karolinska University Hospital, Huddinge, Sweden.
    Flygare, Johan
    Department of Molecular Medicine and Gene Therapy, Lund Stem Cell Center, Lund University, Lund, Sweden..
    Fahlgren, Anna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Cyclin-dependent kinase 8/19 inhibition suppresses osteoclastogenesis by downregulating RANK and promotes osteoblast mineralization and cancellous bone healing.2019In: Journal of Cellular Physiology, ISSN 0021-9541, E-ISSN 1097-4652, Vol. 234, no 9, p. 16503-16516Article in journal (Refereed)
    Abstract [en]

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

    Download full text (pdf)
    fulltext
  • 268.
    Amirhosseini, Mehdi
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Madsen, Rune V.
    Hosp Special Surg, NY 10021 USA.
    Escott, K. Jane
    AstraZeneca, England.
    Bostrom, Mathias P.
    Hosp Special Surg, NY 10021 USA.
    Ross, F. Patrick
    Hosp Special Surg, NY 10021 USA.
    Fahlgren, Anna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    GSK-3 beta inhibition suppresses instability-induced osteolysis by a dual action on osteoblast and osteoclast differentiation2018In: Journal of Cellular Physiology, ISSN 0021-9541, E-ISSN 1097-4652, Vol. 233, no 3, p. 2398-2408Article in journal (Refereed)
    Abstract [en]

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

    Download full text (pdf)
    fulltext
  • 269.
    Amiri Arimi, Somayeh
    et al.
    Shahid Beheshti University of Medical Sciences, Physiotherapy Research Center, School of Rehabilitation, Department of Physiotherapy, Tehran, Iran; University of Social Welfare and Rehabilitation Sciences, Department of Physiotherapy, Tehran, Iran.
    Mohseni Bandpei, Mohammad Ali
    Pediatric Neurorehabilitation Research Center, Department of Physiotherapy, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran; University Institute of Physical Therapy, Faculty of Allied Health Sciences, University of Lahore, Lahore, Pakistan.
    Rezasoltani, Asghar
    Shahid Beheshti University of Medical Sciences, Physiotherapy Research Centre, School of Rehabilitation, Tehran, Iran.
    Peolsson, Anneli
    Linköping University, Department of Medical and Health Sciences, Division of Physiotherapy. Linköping University, Faculty of Medicine and Health Sciences.
    Mohammadi, Masumeh
    Shahid Beheshti University of Medical Sciences, Physiotherapy Research Center, School of Rehabilitation, Department of Physiotherapy, Tehran, Iran.
    Multifidus muscle size changes at different directions of head and neck movements in females with unilateral chronic non-specific neck pain and healthy subjects using ultrasonography2018In: Journal of Bodywork & Movement Therapies, ISSN 1360-8592, E-ISSN 1532-9283, Vol. 22, no 3, p. 560-565Article in journal (Refereed)
    Abstract [en]

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

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

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

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

  • 270.
    Amundstuen Reppe, Linda
    et al.
    Nordic University, Norway; Norwegian University of Science and Technology, Norway; St Olays Hospital, Norway.
    Lydersen, Stian
    Norwegian University of Science and Technology, Norway.
    Schjott, Jan
    Haukeland Hospital, Norway; University of Bergen, Norway; Haukeland Hospital, Norway.
    Damkier, Per
    Odense University Hospital, Denmark.
    Rolighed Christensen, Hanne
    Bispebjerg and Frederiksberg University Hospital, Denmark.
    Peter Kampmann, Jens
    Bispebjerg and Frederiksberg University Hospital, Denmark.
    Böttiger, Ylva
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pharmacology.
    Spigset, Olav
    Norwegian University of Science and Technology, Norway; St Olays Hospital, Norway.
    Relationship Between Time Consumption and Quality of Responses to Drug-related Queries: A Study From Seven Drug Information Centers in Scandinavia2016In: Clinical Therapeutics, ISSN 0149-2918, E-ISSN 1879-114X, Vol. 38, no 7, p. 1738-1749Article in journal (Refereed)
    Abstract [en]

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

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  • 271.
    Amundstuen Reppe, Linda
    et al.
    Nordic University, Norway; Norwegian University of Science and Technology, Norway; St Olavs Hospital, Norway.
    Spigset, Olav
    Norwegian University of Science and Technology, Norway; St Olavs Hospital, Norway.
    Kampmann, Jens Peter
    Bispebjerg Hospital, Denmark.
    Damkier, Per
    Odense University Hospital, Denmark.
    Rolighed Christensen, Hanne
    Bispebjerg Hospital, Denmark.
    Böttiger, Ylva
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pharmacology.
    Schjott, Jan
    Haukeland Hospital, Norway; University of Bergen, Norway; Haukeland Hospital, Norway.
    Quality assessment of structure and language elements of written responses given by seven Scandinavian drug information centres2017In: European Journal of Clinical Pharmacology, ISSN 0031-6970, E-ISSN 1432-1041, Vol. 73, no 5, p. 623-631Article in journal (Refereed)
    Abstract [en]

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

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  • 272.
    Anagnostopoulos, Dimitris C.
    et al.
    University of Athens, Greece.
    Heberbrand, Johannes
    University of Duisburg Essen, Germany.
    Eliez, Stephan
    University of Geneva, Switzerland.
    Doyle, Maeve B.
    St Davnets Hospital, Ireland.
    Klasen, Henrikje
    Leiden University, Netherlands.
    Crommen, Sofie
    Flemish Assoc Child and Adolescent Psychiat, Belgium.
    Cetin Cuhadaroglu, Fusun
    Hacettepe University, Turkey.
    Pejovic-Milovancevic, Milica
    University of Belgrade, Serbia.
    Herreros, Oscar
    Hospital University of Virgen de las Nieves, Spain.
    Minderaa, Ruud
    European Soc Child and Adolescent Psychiat, Belgium.
    Karwautz, Andreas
    Medical University of Vienna, Austria.
    Svedin, Carl Göran
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Child and Adolescent Psychiatry in Linköping.
    Raynaud, Jean Philippe
    Centre Hospital University of Toulouse, France.
    Editorial Material: European Society of Child and Adolescent Psychiatry: position statement on mental health of child and adolescent refugees in EUROPEAN CHILD and ADOLESCENT PSYCHIATRY, vol 25, issue 7, pp 673-6762016In: European Child and Adolescent Psychiatry, ISSN 1018-8827, E-ISSN 1435-165X, Vol. 25, no 7, p. 673-676Article in journal (Other academic)
    Abstract [en]

    n/a

  • 273.
    Andelin, M.
    et al.
    Department of Medicine, NU Hospital Group, Uddevalla, Sweden..
    Kropff, J.
    Department of Endocrinology, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands..
    Matuleviciene, V.
    Institute of Medicine, University of Gothenburg, Gothenburg, Sweden..
    Joseph, J.I.
    Department of Anaesthesiology, Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, PA, USA..
    Attvall, S.
    Institute of Medicine, University of Gothenburg, Gothenburg, Sweden..
    Theodorsson, Elvar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Hirsch, I.B.
    University of Washington, Seattle, WA, USA.
    Imberg, H.
    Statistiska Konsultgruppen, Gothenburg, Sweden..
    Dahlqvist, S.
    Department of Medicine, NU Hospital Group, Uddevalla, Sweden.
    Klonoff, D.
    Diabetes Research Institute, Mills-Peninsula Health Services, San Mateo, CA, USA..
    Haraldsson, B.
    Institute of Medicine, University of Gothenburg, Gothenburg, Sweden..
    DeVries, J.H.
    Department of Endocrinology, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands..
    Lind, M.
    Department of Medicine, NU Hospital Group, Uddevalla, Sweden Institute of Medicine, University of Gothenburg, Gothenburg, Sweden lind.marcus@telia.com..
    Assessing the Accuracy of Continuous Glucose Monitoring (CGM) Calibrated With Capillary Values Using Capillary or Venous Glucose Levels as a Reference.2016In: Journal of Diabetes Science and Technology, E-ISSN 1932-2968, Vol. 10, no 4, p. 876-884Article in journal (Refereed)
    Abstract [en]

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

  • 274.
    Andell, Pontus
    et al.
    Lund Univ, Sweden.
    Berntorp, Karolina
    Lund Univ, Sweden.
    Christiansen, Evald H.
    Aarhus Univ Hosp, Denmark.
    Gudmundsdottir, Ingibjorg J.
    Univ Hosp Iceland, Iceland.
    Sandhall, Lennart
    Helsingborg Hosp, Sweden.
    Venetsanos, Dimitrios
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Erlinge, David
    Lund Univ, Sweden.
    Frobert, Ole
    Orebro Univ, Sweden.
    Koul, Sasha
    Lund Univ, Sweden.
    Reitan, Christian
    Lund Univ, Sweden.
    Gotberg, Matthias
    Lund Univ, Sweden.
    Reclassification of Treatment Strategy With Instantaneous Wave-Free Ratio and Fractional Flow Reserve A Substudy From the iFR-SWEDEHEART Trial2018In: JACC: Cardiovascular Interventions, ISSN 1936-8798, E-ISSN 1876-7605, Vol. 11, no 20, p. 2084-2094Article in journal (Refereed)
    Abstract [en]

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

  • 275.
    Anders Eriksson, Mats
    et al.
    Karolinska Institute, Sweden; Karolinska University Hospital, Sweden; Gothenburg University, Sweden.
    Lieden, Agne
    Karolinska Institute, Sweden; Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
    Westerlund, Joakim
    Stockholm University, Sweden.
    Bremer, Anna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics. Division of Clinical Genetics, University Hospital, Link.
    Wincent, Josephine
    Karolinska Institute, Sweden; Karolinska Institute, Sweden.
    Sahlin, Ellika
    Karolinska Institute, Sweden; Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
    Gillberg, Christopher
    Gothenburg University, Sweden.
    Fernell, Elisabeth
    Gothenburg University, Sweden.
    Anderlid, Britt-Marie
    Karolinska Institute, Sweden; Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
    Rare copy number variants are common in young children with autism spectrum disorder2015In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 104, no 6, p. 610-618Article in journal (Refereed)
    Abstract [en]

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

  • 276.
    Andersen, Pia
    et al.
    Department of Research and Development, Region Kronoberg, Sweden.
    Holmberg, Sara
    Region Kronoberg, Sweden.
    Lendahls, Lena
    Department of Research and Development, Region Kronoberg, Sweden.
    Nilsen, Per
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Kristenson, Margareta
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Physical Activity on Prescription with Counsellor Support: A 4-Year Registry-Based Study in Routine Health Care in Sweden2018In: Healthcare, E-ISSN 2227-9032, Vol. 6, no 2, article id E34Article in journal (Refereed)
    Abstract [en]

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

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

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

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

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  • 277.
    Andersen, Pia
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Reg Kronoberg, Sweden.
    Lendahls, Lena
    Reg Kronoberg, Sweden; Linnaeus Univ, Sweden.
    Holmberg, Sara
    Reg Kronoberg, Sweden; Lund Univ, Sweden.
    Nilsen, Per
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Patients experiences of physical activity on prescription with access to counsellors in routine care: a qualitative study in Sweden2019In: BMC Public Health, ISSN 1471-2458, E-ISSN 1471-2458, Vol. 19, article id 210Article in journal (Refereed)
    Abstract [en]

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

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  • 278.
    Andersen, Åsa
    et al.
    Uppsala University, Sweden.
    Ståhl, Christian
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Anderzen, Ingrid
    Uppsala University, Sweden.
    Kristiansson, Per
    Uppsala University, Sweden.
    Larsson, Kjerstin
    Uppsala University, Sweden.
    Positive experiences of a vocational rehabilitation intervention for individuals on long-term sick leave, the Dirigo project: a qualitative study2017In: BMC Public Health, ISSN 1471-2458, E-ISSN 1471-2458, Vol. 17, article id 790Article in journal (Refereed)
    Abstract [en]

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

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  • 279.
    Anderson, Maria
    et al.
    Karolinska Inst, Sweden; Publ Dent Hlth Serv, Sweden; Ctr Pediat Oral Hlth, Sweden.
    Davidson, Thomas
    Linköping University, Department of Medical and Health Sciences, Division of Health Care Analysis. Linköping University, Faculty of Medicine and Health Sciences.
    Dahllof, Goran
    Karolinska Inst, Sweden; Ctr Pediat Oral Hlth, Sweden.
    Grindefjord, Margaret
    Karolinska Inst, Sweden; Publ Dent Hlth Serv, Sweden; Ctr Pediat Oral Hlth, Sweden.
    Economic evaluation of an expanded caries-preventive program targeting toddlers in high-risk areas in Sweden2019In: Acta Odontologica Scandinavica, ISSN 0001-6357, E-ISSN 1502-3850, Vol. 77, no 4, p. 303-309Article in journal (Refereed)
    Abstract [en]

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

  • 280.
    Anderson, Peter
    et al.
    Newcastle University, England; Maastricht University, Netherlands.
    Bendtsen, Preben
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in West Östergötland, Department of Medical Specialist in Motala.
    Spak, Fredrik
    University of Gothenburg, Sweden.
    Reynolds, Jillian
    Hospital Clin Barcelona, Spain.
    Drummond, Colin
    Kings Coll London, England; South London and Maudsley NHS Fdn Trust, England.
    Segura, Lidia
    Govt Catalonia, Spain.
    Keurhorst, Myrna N.
    Radboud University of Nijmegen, Netherlands.
    Palacio-Vieira, Jorge
    Govt Catalonia, Spain.
    Wojnar, Marcin
    Medical University of Warsaw, Poland.
    Parkinson, Kathryn
    Newcastle University, England.
    Colom, Joan
    Govt Catalonia, Spain.
    Kloda, Karolina
    Pomeranian Medical University, Poland.
    Deluca, Paolo
    Kings Coll London, England.
    Baena, Begona
    Govt Catalonia, Spain.
    Newbury-Birch, Dorothy
    Newcastle University, England.
    Wallace, Paul
    UCL, England.
    Heinen, Maud
    Radboud University of Nijmegen, Netherlands.
    Wolstenholme, Amy
    Kings Coll London, England.
    van Steenkiste, Ben
    Maastricht University, Netherlands.
    Mierzecki, Artur
    Pomeranian Medical University, Poland.
    Okulicz-Kozaryn, Katarzyna
    State Agency Prevent Alcohol Related Problems, Poland.
    Ronda, Gaby
    Maastricht University, Netherlands.
    Kaner, Eileen
    Newcastle University, England.
    Laurant, Miranda G. H.
    Radboud University of Nijmegen, Netherlands; HAN University of Appl Science, Netherlands.
    Coulton, Simon
    University of Kent, England.
    Gual, Toni
    Hospital Clin Barcelona, Spain.
    Improving the delivery of brief interventions for heavy drinking in primary health care: outcome results of the Optimizing Delivery of Health Care Intervention (ODHIN) five-country cluster randomized factorial trial2016In: Addiction, ISSN 0965-2140, E-ISSN 1360-0443, Vol. 111, no 11, p. 1935-1945Article in journal (Refereed)
    Abstract [en]

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

  • 281.
    Anderson, Peter
    et al.
    Newcastle University, England; Maastricht University, Netherlands.
    Coulton, Simon
    University of Kent, England.
    Kaner, Eileen
    Newcastle University, England.
    Bendtsen, Preben
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in West Östergötland, Department of Medical Specialist in Motala.
    Kloda, Karolina
    Pomeranian Medical University, Poland.
    Reynolds, Jillian
    Hospital Clin Barcelona, Spain.
    Segura, Lidia
    Govt Catalonia, Spain.
    Wojnar, Marcin
    Medical University of Warsaw, Poland.
    Mierzecki, Artur
    Pomeranian Medical University, Poland.
    Deluca, Paolo
    Kings Coll London, England.
    Newbury-Birch, Dorothy
    University of Teesside, England.
    Parkinson, Kathryn
    Newcastle University, England.
    Okulicz-Kozaryn, Katarzyna
    State Agency Prevent Alcohol Related Problems, Poland.
    Drummond, Colin
    Kings Coll London, England; South London and Maudsley NHS Fdn Trust, England.
    Gual, Antoni
    Hospital Clin Barcelona, Spain.
    Delivery of Brief Interventions for Heavy Drinking in Primary Care: Outcomes of the ODHIN 5-Country Cluster Randomized Trial2017In: Annals of family medicine (online), ISSN 1544-1709, E-ISSN 1544-1717, Vol. 15, no 4, p. 335-340Article in journal (Refereed)
    Abstract [en]

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

  • 282.
    Anderson, Peter
    et al.
    Newcastle University, England; Maastricht University, Netherlands.
    Kaner, Eileen
    Newcastle University, England.
    Keurhorst, Myrna
    Radboud University of Nijmegen, Netherlands; Saxion University of Appl Science, Netherlands.
    Bendtsen, Preben
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in West Östergötland, Department of Medical Specialist in Motala.
    van Steenkiste, Ben
    Maastricht University, Netherlands.
    Reynolds, Jillian
    IDIBAPS, Spain.
    Segura, Lidia
    Govt Catalonia, Spain.
    Wojnar, Marcin
    Medical University of Warsaw, Poland.
    Kloda, Karolina
    Pomeranian Medical University, Poland.
    Parkinson, Kathryn
    Newcastle University, England.
    Drummond, Colin
    Kings Coll London, England; Maudsley NHS Fdn Trust, England.
    Okulicz-Kozaryn, Katarzyna
    State Agency Prevent Alcohol Related Problems, Poland.
    Mierzecki, Artur
    Pomeranian Medical University, Poland.
    Laurant, Miranda
    Radboud University of Nijmegen, Netherlands; HAN University of Appl Science, Netherlands.
    Newbury-Birch, Dorothy
    University of Teesside, England.
    Gual, Antoni
    IDIBAPS, Spain.
    Attitudes and Learning through Practice Are Key to Delivering Brief Interventions for Heavy Drinking in Primary Health Care: Analyses from the ODHIN Five Country Cluster Randomized Factorial Trial2017In: International Journal of Environmental Research and Public Health, ISSN 1661-7827, E-ISSN 1660-4601, Vol. 14, no 2, article id 121Article in journal (Refereed)
    Abstract [en]

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

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  • 283.
    Anderson, Peter
    et al.
    Newcastle Univ, England; Maastricht Univ, Netherlands.
    Kloda, Karolina
    Pomeranian Med Univ, Poland.
    Kaner, Eileen
    Newcastle Univ, England.
    Reynolds, Jillian
    Hosp Clin Barcelona, Spain.
    Bendtsen, Preben
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in West Östergötland, Department of Medical Specialist in Motala.
    Pelgrum-Keurhorst, Myrna N.
    Radboud Univ Nijmegen, Netherlands; Saxion Univ Appl Sci, Netherlands.
    Segura, Lidia
    Govt Catalonia, Spain.
    Wojnar, Marcin
    Med Univ Warsaw, Poland.
    Mierzecki, Artur
    Pomeranian Med Univ, Poland.
    Deluca, Paolo
    King’s College London, London, UK.
    Newbury-Birch, Dorothy
    Teesside Univ, England.
    Parkinson, Kathryn
    Newcastle Univ, England; State Agcy Prevent Alcohol Related Problems, Poland.
    Okulicz-Kozaryn, Katarzyna
    State Agency for Prevention of Alcohol-Related Problems, Warsaw, Poland.
    Drummond, Colin
    Kings Coll London, England; South London and Maudsley NHS Fdn Trust, England.
    Laurant, Miranda G. H.
    Radboud Univ Nijmegen, Netherlands; HAN Univ Appl Sci, Netherlands.
    Gual, Antoni
    Neurosciences Institute, Hospital Clinic, IDIBAPS, Barcelona, Spain.
    Impact of practice, provider and patient characteristics on delivering screening and brief advice for heavy drinking in primary healthcare: Secondary analyses of data from the ODHIN five-country cluster randomized factorial trial2017In: European Journal of General Practice, ISSN 1381-4788, E-ISSN 1751-1402, Vol. 23, no 1, p. 241-245Article in journal (Refereed)
    Abstract [en]

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

  • 284. Order onlineBuy this publication >>
    Andersson, Anna-Maria
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Mycobacterium tuberculosis and HIV coinfection: Effects on innate immunity and strategies to boost the immune response2019Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

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

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

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

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

    List of papers
    1. Autophagy induction targeting mTORC1 enhances Mycobacterium tuberculosis replication in HIV co-infected human macrophages
    Open this publication in new window or tab >>Autophagy induction targeting mTORC1 enhances Mycobacterium tuberculosis replication in HIV co-infected human macrophages
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    2016 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, no 28171Article in journal (Refereed) Published
    Abstract [en]

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

    Place, publisher, year, edition, pages
    NATURE PUBLISHING GROUP, 2016
    National Category
    Infectious Medicine
    Identifiers
    urn:nbn:se:liu:diva-132355 (URN)10.1038/srep28171 (DOI)000384609100002 ()27302320 (PubMedID)
    Available from: 2016-11-12 Created: 2016-11-01 Last updated: 2019-03-28
    2. HIV Interferes with Mycobacterium tuberculosis Antigen Presentation in Human Dendritic Cells
    Open this publication in new window or tab >>HIV Interferes with Mycobacterium tuberculosis Antigen Presentation in Human Dendritic Cells
    Show others...
    2016 (English)In: American Journal of Pathology, ISSN 0002-9440, E-ISSN 1525-2191, Vol. 186, no 12, p. 3083-3093Article in journal (Refereed) Published
    Abstract [en]

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

    Place, publisher, year, edition, pages
    ELSEVIER SCIENCE INC, 2016
    National Category
    Immunology in the medical area
    Identifiers
    urn:nbn:se:liu:diva-133376 (URN)10.1016/j.ajpath.2016.08.003 (DOI)000389103800003 ()27746182 (PubMedID)
    Note

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

    Available from: 2016-12-27 Created: 2016-12-22 Last updated: 2019-03-28
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  • 285.
    Andersson, Anna-Maria
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Andersson, Blanka
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Lorell, Christoffer
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Raffetseder, Johanna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Larsson, Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Blomgran, Robert
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Autophagy induction targeting mTORC1 enhances Mycobacterium tuberculosis replication in HIV co-infected human macrophages2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, no 28171Article in journal (Refereed)
    Abstract [en]

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

    Download full text (pdf)
    fulltext
  • 286.
    Andersson, Asa
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Vilhelmsson, Mattias
    Reg Hosp Vaxjo, Sweden.
    Fomichov Casaballe, Victoria
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Business support and Development, Regional Cancer Center.
    Lindhoff Larsson, Anna
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Björnsson, Bergthor
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Sandström, Per
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Drott, Jenny
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Nursing Sciences and Reproductive Health. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Patient involvement in surgical care-Healthcare personnel views and behaviour regarding patient involvement2020In: Scandinavian Journal of Caring Sciences, ISSN 0283-9318, E-ISSN 1471-6712Article in journal (Refereed)
    Abstract [en]

    Background All professions in surgical care have a responsibility to include patients in their health care. By Swedish law, all care should be done in dialogue with the patient. The essential part of health care is the meeting between patient and healthcare professional. In the interaction, a decision can be made, and needs can be identified to a safer care. Previous studies on patient participation have focussed on patients perspectives in surgical care, but there is a paucity of studies about the personnels perspective of estimated patient involvement in surgical care. Aim The aim of this study was to identify and describe healthcare personnels view and behaviour regarding patient involvement in surgical care. Method A quantitative study with various professions was conducted. A validated questionnaire was used, remaining questions grouped under following areas: patient involvement, acute phase, hospital time, discharge phase and questions on employment and workplace. Results A total of 140 questionnaires were sent out to a surgical clinic in Sweden, and 102 questionnaires were answered. All professionals stated that clear information is an important part of patient involvement in surgical care. Statistically significant differences existed between the professions in the subscale information. Physicians rated their information higher than the Registered Nurses (p = 0.005) and the practical nurses did (p = 0.001). Hindrances to involving patients were lack of time and other priority tasks. Conclusions Professionals in surgical care graded information to be the most important thing for patient involvement. Participation in important decisions, including the possibility to express personal views and ask questions, is important factors for patient involvement. Barriers against patient involvement are lack of time and prioritisation of other work activities.

    The full text will be freely available from 2021-01-31 15:54
  • 287.
    Andersson, B.
    et al.
    University of Gothenburg, Sweden.
    Swolin-Eide, D.
    University of Gothenburg, Sweden.
    Kristroem, B.
    Umeå University, Sweden.
    Gelander, L.
    University of Gothenburg, Sweden; Angered Hospital, Sweden.
    Magnusson, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry. Linköping University, Faculty of Medicine and Health Sciences.
    Albertsson-Wikland, K.
    University of Gothenburg, Sweden.
    Seasonal variations in vitamin D in relation to growth in short prepubertal children before and during first year growth hormone treatment2015In: Journal of Endocrinological Investigation, ISSN 0391-4097, E-ISSN 1720-8386, Vol. 38, no 12, p. 1309-1317Article in journal (Refereed)
    Abstract [en]

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

  • 288. Order onlineBuy this publication >>
    Andersson, Bengt-Åke
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Department of Laboratory Medicine, Region Jönköping County.
    Circulating Biomarkers in Patients with Head and Neck Cancer and the Influence of Cigarette Smoking2019Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Head and neck cancer (HNC) is a collective name for heterogeneous tumors located in the head and neck regions for which smoking, alcohol and human papillomavirus (HPV) are documented risk factors. The survival of HNC patients has only improved marginally during the last decade. The most important prognostic factors are tumor size, local spread and distant metastases, tumor node metastasis (TNM) staging. Prognostic biomarkers are needed as a complement to TNM staging.

    The aim for this thesis was to investigate rapid and low cost blood based biomarkers which could indicate the risk of HNC, recurrence of the disease or the survival of HNC patients. Furthermore, the aim was to examine how cigarette smoking influences the levels of biomarkers.

    In paper I, a possible role of plasma cytokines or proteins associated with immune response or inflammation, as biomarkers for the survival of HNC patients was investigated. Higher levels of C-reactive protein (CRP) and tumor necrosis factor alpha (TNF-α) were detected in plasma of the patients compared with the levels in the controls. The elevated levels of these two biomarkers detected in patients were associated with decreased survival.

    In paper II, the influence of 45 single nucleotide polymorphisms (SNPs) located in 41 genes associated with cell cycle progression, cell death, DNA repair or immune response on cancer risk, tumor recurrence and survival in HNC patients were investigated. SNPs in immune response genes were associated with risk for HNC, an elevated risk for recurrence and a decreased survival in HNC patients.

    In paper III, the influence of cigarette smoking on levels of inflammatory cells, proteins or cytokines/chemokines, microRNAs (miRNAs) and SNPs was analysed in healthy smokers and non-smokers. Higher levels of total white blood cells (WBCs), neutrophils, monocytes, lymphocytes, neutrophil to lymphocyte ratio (NLR), CRP, monocyte chemoattractant protein- 1 (MCP-1) and interferon gamma (IFN-γ) were detected in smokers compared to non-smokers and indicate an inflammatory response. Also, a lower level of oncomiRNA miR-21was detected in smokers. This alteration, in combination with the elevated levels of IFN-γ in smokers could be a protective response to cigarette smoke. The higher levels of IFN-γ in smokers compared to non-smokers were however only detected in individuals with SNP rs2069705 genotype AG/GG. This indicates a genetic association of the levels of IFN-γ.

    In paper IV, the separate effects of cigarette smoking and HNC on inflammatory or immune biomarkers and the impact of high risk human papillomavirus, age and gender were investigated. Comparisons of circulating levels of WBCs and its subpopulations, plasma proteins or cytokines/chemokines between smoking and non-smoking patients, smoking and non-smoking controls and between the patient and control groups were analysed. Smoking had highest impact on elevated levels of WBCs, IFN-γ and MCP-1, and HNC had highest impact on elevated levels of neutrophils, monocytes, NLR, CRP, macrophage inflammatory protein 1 beta and TNF-α.

    In conclusion, host immune response associated parameters could be suitable as biomarkers for the risk of HNC, risk of recurrence or in predicting survival of HNC patients. This thesis show that HNC are associated with systemic inflammatory response and upregulated CRP and TNF-α is related to shorter survival in HNC patients. Additionally, SNPs in immune response genes such as rs1800629 in the TNF-α gene indicates a risk for HNC or an elevated risk for recurrence and a decreased survival in HNC patients. These rapid and low cost blood based biomarkers could be used in combination or as a supplement to established biomarkers in the clinic for a more personalized treatment modality.

    List of papers
    1. Plasma tumor necrosis factor-α and C-reactive protein as biomarker for survival in head and neck squamous cell carcinoma.
    Open this publication in new window or tab >>Plasma tumor necrosis factor-α and C-reactive protein as biomarker for survival in head and neck squamous cell carcinoma.
    Show others...
    2014 (English)In: Journal of Cancer Research and Clinical Oncology, ISSN 0171-5216, E-ISSN 1432-1335, Vol. 140, no 3, p. 515-519Article in journal (Refereed) Published
    Abstract [en]

    PURPOSE: Tumor TNM staging is the main basis for prognosis and treatment decision for head and neck squamous cell carcinoma (HNSCC) despite significant heterogeneity in terms of outcome among patients with the same clinical stage. In this study, a possible role of plasma interleukin-2 (IL-2), interleukin-6 (IL-6), granulocyte-macrophage colony-stimulating factor (GM-CSF), tumor necrosis factor-α (TNF-α) and C-reactive protein (CRP) as biomarkers for survival of HNSCC patients was investigated.

    METHODS: In this prospective study, plasma levels of IL-2, IL-6, GM-CSF, TNF-α and CRP in patients (n = 100) and controls (n = 48) were analyzed.

    RESULTS: Significantly elevated levels of CRP and TNF-α (p < 0.001) were found in the patients. Combination of upregulated CRP and TNF-α in the patient plasma was significantly related to shorter patient survival, independent of clinical stage.

    CONCLUSIONS: Our findings indicate that CRP and TNF-α might be suitable as biomarkers in combination with tumor TNM staging for predicting survival and individualized treatment of HNSCC patients. Plasma CRP and TNF-α analysis are simple, rapid, cost effective and suitable for clinical practice.

    Keywords
    Head and neck squamous cell carcinoma, Biomarkers, Survival, CRP, TNF-α
    National Category
    Cancer and Oncology
    Identifiers
    urn:nbn:se:liu:diva-162092 (URN)10.1007/s00432-014-1592-8 (DOI)24481866 (PubMedID)
    Available from: 2019-11-19 Created: 2019-11-19 Last updated: 2019-11-19Bibliographically approved
    2. Single-Nucleotide Polymorphisms and Cancer Risk, Tumor Recurrence, or Survival of Head and Neck Cancer Patients
    Open this publication in new window or tab >>Single-Nucleotide Polymorphisms and Cancer Risk, Tumor Recurrence, or Survival of Head and Neck Cancer Patients
    Show others...
    2017 (English)In: Oncology, ISSN 0030-2414, E-ISSN 1423-0232, Vol. 92, no 3, p. 161-169Article in journal (Refereed) Published
    Abstract [en]

    Objective: This paper aims at studying the influence of single-nucleotide polymorphisms (SNPs) on cancer risk, tumor recurrence, and survival in head and neck (Hamp;N) cancer patients. Methods: A total of 45 SNPs in 41 genes were investigated. A total of 174 Caucasian Hamp;N cancer patients and 245 healthy blood donors were enrolled in the study. Results: Ten SNPs were associated with Hamp;N cancer risk, but the identified SNPs differed among males and females. Some of the SNPs were related to immune response genes. The immune response gene SNPs were also related to survival. In particular, we noted that the tumor necrosis factor alpha (TNF alpha) rs1800629 could have an influence on cancer risk; tumor recurrence as well as survival. Conclusion: Genetic variation of the TNFa rs1800629 might be useful as a biomarker in clinical decision-making since it was found to be related to cancer risk, tumor recurrence, and survival of Hamp;N cancer patients. (C) 2016 S. Karger AG, Basel

    Place, publisher, year, edition, pages
    KARGER, 2017
    Keywords
    Head and neck cancer; Tumor recurrence; Survival time; Single-nucleotide polymorphisms
    National Category
    Cancer and Oncology
    Identifiers
    urn:nbn:se:liu:diva-136217 (URN)10.1159/000452278 (DOI)000395366800005 ()27997918 (PubMedID)
    Note

    Funding Agencies|Jonkoping Clinical Cancer Research Foundation; Futurum; FORSS; Swedish Laryngeal Foundation

    Available from: 2017-03-31 Created: 2017-03-31 Last updated: 2019-11-19
    3. Cigarette smoking affects microRNAs and inflammatory biomarkers in healthy individuals and an association to single nucleotide polymorphisms is indicated
    Open this publication in new window or tab >>Cigarette smoking affects microRNAs and inflammatory biomarkers in healthy individuals and an association to single nucleotide polymorphisms is indicated
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    2019 (English)In: Biomarkers, ISSN 1354-750X, E-ISSN 1366-5804, Vol. 24, no 2, p. 180-185Article in journal (Refereed) Published
    Abstract [en]

    Background: Cigarette smoke induces inflammation and remodels immune response. Genetic and epigenetic alterations might be involved in the pathogenesis of smoking related diseases. In this study, we investigated the effect of smoking on systemic inflammation biomarkers and epigenetic changes at microRNA (miRNA) expression level. We also examined if the levels of inflammatory biomarkers were associated with selected single nucleotide polymorphisms (SNPs). Method: From 39 smokers and 101 non-smokers, levels of total white blood cells (WBCs) and its subpopulations, plasma cytokines/chemokines/proteins and miRNAs were analysed. For three biomarkers, C-reactive protein (CRP), MCP-1 and IFN-gamma that were affected by smoking, the influence of SNPs was analyzed. Result: Elevated levels of total WBCs, neutrophils, monocytes, lymphocytes, CRP, MCP-1, IFN-gamma and lower levels of miR-21 were detected in smokers. The elevated levels of IFN-gamma in smokers was only statistically significantly associated with rs2069705 AG/GG SNP-genotype. Conclusions: A lower level of oncomir miRNA-21 and a higher level of immune modelling cytokine IFN-gamma detected in smokers could be a protective immune response to cigarette smoke. The higher level of IFN-gamma in smokers with a specific SNP genotype also suggests that a genetic interaction with smoking might predict the pathobiology of smoking related disease.

    Place, publisher, year, edition, pages
    TAYLOR & FRANCIS LTD, 2019
    Keywords
    Immune respons; single nucleotide polymorphism; microRNA; smoking related diseases; cigarette smoking
    National Category
    Rheumatology and Autoimmunity
    Identifiers
    urn:nbn:se:liu:diva-157272 (URN)10.1080/1354750X.2018.1539764 (DOI)000465158700011 ()30375257 (PubMedID)
    Note

    Funding Agencies|Forskningsradet i Sydostra Sverige; Futurum-Academy of HealthCare at Jonkoping County Council [477461, 490031, 669631]; Foundation of Clinical Cancer Research in Jo nkoping [110426-1]; Medical Research Council of Southeast Sweden (FORSS) [567001]

    Available from: 2019-06-12 Created: 2019-06-12 Last updated: 2019-11-19
    4. Impact of Cigarette Smoking and Head and Neck Squamous Cell Carcinoma on Circulating Inflammatory Biomarkers
    Open this publication in new window or tab >>Impact of Cigarette Smoking and Head and Neck Squamous Cell Carcinoma on Circulating Inflammatory Biomarkers
    Show others...
    2020 (English)In: Oncology, ISSN 0030-2414, E-ISSN 1423-0232, Vol. 98, no 1, p. 42-47Article in journal (Refereed) Published
    Abstract [en]

    INTRODUCTION: Smoking induces inflammation and an immune response. A cancer-related inflammatory response has been seen in smoking and nonsmoking head and neck squamous cell carcinoma (HNSCC) patients.

    OBJECTIVES: The aim of this study was to analyze the possible separated effects of smoking or HNSCC on 18 inflammatory or immune regulatory biomarkers.

    METHODS: Fifty-one nonsmoking and 36 smoking pretreated HNSCC patients and 101 nonsmoking and 39 smoking controls were included in this study. The levels of 18 inflammatory or immune regulatory biomarkers were analyzed. A multivariable linear regression model was used to predict the impact of smoking and HNSCC on the levels of the biomarkers.

    RESULTS: Smoking had the highest impact on total WBC, IFN-γ, and MCP-1 levels. The highest impact of HNSCC was found on neutrophils, neutrophil-to-lymphocyte ratio, HsCRP, MIP-1b, and TNF-α levels.

    CONCLUSION: Identifying HNSCC or smoking-related inflammatory biomarkers might contribute to the understanding of the immune response in HNSCC patients. This study could provide information of inflammatory biomarkers in HNSCC patients.

    Place, publisher, year, edition, pages
    S. Karger, 2020
    Keywords
    Biomarkers, Head and neck squamous cell carcinoma, Immune response, Inflammation, Smoking
    National Category
    Cancer and Oncology
    Identifiers
    urn:nbn:se:liu:diva-162093 (URN)10.1159/000502651 (DOI)000522873100007 ()31437849 (PubMedID)
    Note

    Funding agencies: 

    Futurum-Academy of HealthCare at Jonkoping County Council [696261]; Foundation of Clinical Cancer Research in Jonkoping [110426]

    Available from: 2019-11-19 Created: 2019-11-19 Last updated: 2020-04-21Bibliographically approved
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  • 289.
    Andersson, Bengt-Åke
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences. Department of Laboratory Medicine, Region Jönköping County.
    Löfgren, Sture
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences. Department of Laboratory Medicine, Region Jönköping County.
    Lewin, Freddi
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences. Department of Oncology, Region Jönköping County.
    Nilsson, Mats
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences. Futurum, Academy for Health and Care, Jönköping.
    Laytragoon-Lewin, Nongnit
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Department of Laboratory Medicine, Region Jönköping County.
    Impact of Cigarette Smoking and Head and Neck Squamous Cell Carcinoma on Circulating Inflammatory Biomarkers2020In: Oncology, ISSN 0030-2414, E-ISSN 1423-0232, Vol. 98, no 1, p. 42-47Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: Smoking induces inflammation and an immune response. A cancer-related inflammatory response has been seen in smoking and nonsmoking head and neck squamous cell carcinoma (HNSCC) patients.

    OBJECTIVES: The aim of this study was to analyze the possible separated effects of smoking or HNSCC on 18 inflammatory or immune regulatory biomarkers.

    METHODS: Fifty-one nonsmoking and 36 smoking pretreated HNSCC patients and 101 nonsmoking and 39 smoking controls were included in this study. The levels of 18 inflammatory or immune regulatory biomarkers were analyzed. A multivariable linear regression model was used to predict the impact of smoking and HNSCC on the levels of the biomarkers.

    RESULTS: Smoking had the highest impact on total WBC, IFN-γ, and MCP-1 levels. The highest impact of HNSCC was found on neutrophils, neutrophil-to-lymphocyte ratio, HsCRP, MIP-1b, and TNF-α levels.

    CONCLUSION: Identifying HNSCC or smoking-related inflammatory biomarkers might contribute to the understanding of the immune response in HNSCC patients. This study could provide information of inflammatory biomarkers in HNSCC patients.

  • 290.
    Andersson, Bengt-Åke
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Ryhov Cty Hosp, Sweden.
    Sayardoust, Shariel
    Inst Postgrad Dent Educ, Sweden.
    Lofgren, Sture
    Ryhov Cty Hosp, Sweden.
    Rutqvist, Lars Erik
    Swedish Match AB, Sweden.
    Lewin, Nongnit
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Ryhov Cty Hosp, Sweden.
    Cigarette smoking affects microRNAs and inflammatory biomarkers in healthy individuals and an association to single nucleotide polymorphisms is indicated2019In: Biomarkers, ISSN 1354-750X, E-ISSN 1366-5804, Vol. 24, no 2, p. 180-185Article in journal (Refereed)
    Abstract [en]

    Background: Cigarette smoke induces inflammation and remodels immune response. Genetic and epigenetic alterations might be involved in the pathogenesis of smoking related diseases. In this study, we investigated the effect of smoking on systemic inflammation biomarkers and epigenetic changes at microRNA (miRNA) expression level. We also examined if the levels of inflammatory biomarkers were associated with selected single nucleotide polymorphisms (SNPs). Method: From 39 smokers and 101 non-smokers, levels of total white blood cells (WBCs) and its subpopulations, plasma cytokines/chemokines/proteins and miRNAs were analysed. For three biomarkers, C-reactive protein (CRP), MCP-1 and IFN-gamma that were affected by smoking, the influence of SNPs was analyzed. Result: Elevated levels of total WBCs, neutrophils, monocytes, lymphocytes, CRP, MCP-1, IFN-gamma and lower levels of miR-21 were detected in smokers. The elevated levels of IFN-gamma in smokers was only statistically significantly associated with rs2069705 AG/GG SNP-genotype. Conclusions: A lower level of oncomir miRNA-21 and a higher level of immune modelling cytokine IFN-gamma detected in smokers could be a protective immune response to cigarette smoke. The higher level of IFN-gamma in smokers with a specific SNP genotype also suggests that a genetic interaction with smoking might predict the pathobiology of smoking related disease.

  • 291.
    Andersson, Bjorn
    et al.
    University of Gothenburg, Sweden.
    Swolin-Eide, Diana
    University of Gothenburg, Sweden.
    Magnusson, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Albertsson-Wikland, Kerstin
    University of Gothenburg, Sweden.
    Short-term changes in bone formation markers following growth hormone (GH) treatment in short prepubertal children with a broad range of GH secretion2015In: Clinical Endocrinology, ISSN 0300-0664, E-ISSN 1365-2265, Vol. 82, no 1, p. 91-99Article in journal (Refereed)
    Abstract [en]

    ObjectivesGrowth hormone (GH) promotes longitudinal growth and bone modelling/remodelling. This study investigated the relationship between levels of bone formation markers and growth during GH treatment in prepubertal children with widely ranging GH secretion levels. MethodsThe study group comprised 113 short prepubertal children (mean ageSD, 937213years; 99 boys) on GH treatment (330 +/- 006g/kg/day) for 1year. Blood samples were taken at baseline and 1 and 2weeks, 1 and 3months, and 1year after treatment start. Intact amino-terminal propeptide of type I procollagen (PINP), bone-specific alkaline phosphatase (BALP) and osteocalcin were measured using an automated IDS-iSYS immunoassay system. ResultsIntact amino-terminal propeptide of type I procollagen (PINP), BALP and osteocalcin, increased in the short-term during GH treatment. PINP after 1week (P=000077), and BALP and osteocalcin after 1month (Pless than00001 and P=00043, respectively). PINP levels at 1 and 3months correlated positively, and osteocalcin levels at 1week and percentage change after 1month correlated negatively, with first year growth response. No significant correlations were found between BALP and first year growth. Multiple regression analysis showed that bone marker levels together with auxological data and insulin-like growth factor binding protein-3 explained the variation in first year growth response to 36% at start, 32% after 2weeks and 48% at 3months. ConclusionShort-term increases in levels of the bone formation markers PINP, BALP and osteocalcin showed different temporal patterns, but all correlated with first year growth response during GH treatment. These markers may be a useful addition to existing prediction models for growth response.

  • 292.
    Andersson, Björn
    et al.
    Institution of Clinical Sciences/Pediatrics, Umeå University, Umeå, Sweden.
    Swolin-Eide, Diana
    Göteborg Pediatric Growth Research Center (GP-GRC), Department of Pediatrics, Institute of Clinical Sciences, The Sahlgrenska Academy at the University of Gothenburg, Göteborg, Sweden.
    Magnusson, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Albertsson-Wikland, Kerstin
    Department of Physiology/Division of Endocrinology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Göteborg, Sweden.
    Vitamin D status in children over three decades – do children get enough vitamin D?2016In: Bone Reports, ISSN 2352-1872, Vol. 5, p. 150-152Article in journal (Refereed)
    Abstract [en]

    Vitamin D is a key player in the endocrine regulation of calcium and phosphate metabolism and plays a pivotal role in the acquisition of bone mass during childhood. This study investigated long-term data of vitamin D levels in children and adolescents between 1 and 18 years of age. Serum 25-hydroxyvitamin D (25(OH)D) was analyzed between 1982 and 2013 in 2048 Swedish Caucasian children (mean age ± SD, 8.59 ± 3.68 years; 1197 boys). Overall, 704 (34%) children had below recommended levels of 50 nmol/L; however, only 63 (3%) had levels below 25 nmol/L, i.e., vitamin D deficiency. No trend for decreased vitamin D levels over time was found in this population, with median 25(OH)D levels of 58.4 nmol/L, minimum–maximum 5.0–159.3 nmol/L. Younger children, independent of gender, had significantly higher levels 25(OH)D.

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    Vitamin D status in children over three decades – do children get enough vitamin D?
  • 293.
    Andersson, Charlotta
    et al.
    Region Östergötland, Center for Diagnostics, Department of Clinical Physiology in Norrköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Kihlberg, Johan
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping.
    Ebbers, Tino
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Lindström, Lena
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Carlhäll, Carljohan
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Engvall, Jan
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Phase-contrast MRI volume flow - a comparison of breath held and navigator based acquisitions2016In: BMC Medical Imaging, ISSN 1471-2342, E-ISSN 1471-2342, Vol. 16, no 26Article in journal (Refereed)
    Abstract [en]

    Background: Magnetic Resonance Imaging (MRI) 2D phase-contrast flow measurement has been regarded as the gold standard in blood flow measurements and can be performed with free breathing or breath held techniques. We hypothesized that the accuracy of flow measurements obtained with segmented phase-contrast during breath holding, and in particular higher number of k-space segments, would be non-inferior compared to navigator phase-contrast. Volumes obtained from anatomic segmentation of cine MRI and Doppler echocardiography were used for additional reference. Methods: Forty patients, five women and 35 men, mean age 65 years (range 53-80), were randomly selected and consented to the study. All underwent EKG-gated cardiac MRI including breath hold cine, navigator based free-breathing phase-contrast MRI and breath hold phase-contrast MRI using k-space segmentation factors 3 and 5, as well as transthoracic echocardiography within 2 days. Results: In navigator based free-breathing phase-contrast flow, mean stroke volume and cardiac output were 79.7 +/- 17.1 ml and 5071 +/- 1192 ml/min, respectively. The duration of the acquisition was 50 +/- 6 s. With k-space segmentation factor 3, the corresponding values were 77.7 ml +/- 17.5 ml and 4979 +/- 1211 ml/min (p = 0.15 vs navigator). The duration of the breath hold was 17 +/- 2 s. K-space segmentation factor 5 gave mean stroke volume 77.9 +/- 16.4 ml, cardiac output 5142 +/- 1197 ml/min (p = 0.33 vs navigator), and breath hold time 11 +/- 1 s. Anatomical segmentation of cine gave mean stroke volume and cardiac output 91.2 +/- 20.8 ml and 5963 +/- 1452 ml/min, respectively. Echocardiography was reliable in 20 of the 40 patients. The mean diameter of the left ventricular outflow tract was 20.7 +/- 1.5 mm, stroke volume 78.3 ml +/- 15.2 ml and cardiac output 5164 +/- 1249 ml/min. Conclusions: In forty consecutive patients with coronary heart disease, breath holding and segmented k-space sampling techniques for phase-contrast flow produced stroke volumes and cardiac outputs similar to those obtained with free-breathing navigator based phase-contrast MRI, using less time. The values obtained agreed fairly well with Doppler echocardiography while there was a larger difference when compared with anatomical volume determinations using SSFP (steady state free precession) cine MRI.

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  • 294.
    Andersson, Christer
    et al.
    Region Östergötland, Operations management Region Östergötland, Övrig enhet.
    Magnusson, Martin
    Region Östergötland, Operations management Region Östergötland, Övrig enhet.
    Sjödahl, Rune
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Mortalitet bland sjukhusvårdade tycktes inte öka under sommaren [Mortality among hospitalized patients did not appear to increase during the summer]2019In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 116Article in journal (Refereed)
    Abstract [en]

    A retrospective review of medical records (2017-2018) at Linköping University Hospital compared hospital mortality for the 2-month period of summer vacations (group A) with two months of regular activity (group B). The mortality was 163 patients in group A and 216 in group B. Emergency admittance dominated (95%) in both groups. Comorbidity was found in 81%, and at admittance the risk for death during the hospital stay was estimated to more than 50% in three out of four patients. There was no difference between the groups regarding demography, hospital stay, or diagnosis. Due to a 30% reduction of hospital beds during the summer some patients were relocated to other specialties. No relocated patient died in group A but six in group B. Eight deaths were judged as probably preventable, but none definitely preventable. The similarity between the groups regarding mortality does not allow estimations of differences in adverse events in general. Low mortality among relocated patients is probably due to identification of high-risk patients not suitable for relocation.

  • 295.
    Andersson, Christoffer R.
    et al.
    Örebro University, Sweden.
    Bergquist, Jonas
    Uppsala University, Sweden.
    Theodorsson, Elvar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Ström, Jakob
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry. Örebro University, Sweden.
    Comparisons between commercial salivary testosterone enzyme-linked immunosorbent assay kits2017In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 77, no 8, p. 582-586Article in journal (Refereed)
    Abstract [en]

    Introduction: Measuring testosterone concentrations is of interest both in clinical situations and for research, the latter expanding rapidly during recent years. An increased demand for convenient methods has prompted a number of companies to develop enzyme-linked immunosorbent assay (ELISA) kits to measure testosterone concentrations in saliva. However, the inter-comparability of kits from different manufacturers have yet to be determined. Aim of study: The aim of this study was to compare commercially available ELISA kits from four different manufacturers (Salimetrics, IBL, DRG and Demeditec). Methods: Saliva was collected from 50 participants (25 men and 25 women). Each sample was analysed by the four ELISA kits. Results: The correlations between the ELISA kits from Demeditec, DRG and Salimetrics were moderate to high with r-values amp;gt;.77; however, proportional errors between the methods calls for caution. The ELISA kit from IBL malfunctioned and no results from this kit was obtained. Conclusions: Results from studies using the ELISA kits from Demeditec, DRG and Salimetrics are generally comparable; however, translation using the formulae presented in the current study could increase the accuracy of these comparisons.

  • 296.
    Andersson, Ellen
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Norrköping.
    Albertsson, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Holmqvist, Annica
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    GRACE: Geriatric patients tReated with Avastin in CRC multiple linEs2017In: Clinical Practice, ISSN 2044-9038, E-ISSN 2044-9046, Vol. 14, no 3, p. 175-182Article in journal (Refereed)
    Abstract [en]

    Continuous treatment with bevacizumab in elderly patients with mCRC: A phase IV prospective, open-label, single-arm trial to evaluate outcomes and safety with continuous bevacizumab treatment in combination with chemotherapy over disease progression.

  • 297.
    Andersson, Fredrik
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Health Care Analysis. Linköping University, Faculty of Medicine and Health Sciences. Ferring Pharmaceut AS, Denmark.
    Anderson, Peter
    Adelphi Real World, England.
    Holm-Larsen, Tove
    Pharma Evidence, Denmark.
    Piercy, James
    Adelphi Real World, England.
    Everaert, Karel
    Ghent University Hospital, Belgium.
    Holbrook, Tim
    Adelphi Real World, England.
    Assessing the impact of nocturia on health-related quality-of-life and utility: results of an observational survey in adults2016In: JOURNAL OF MEDICAL ECONOMICS, ISSN 1369-6998, Vol. 19, no 12, p. 1200-1206Article in journal (Refereed)
    Abstract [en]

    Background and aim: The impact of nocturia (getting up at night to void) on health-related quality-of-life (HRQoL) is often under-estimated. This study investigated the relative burden in terms of HRQoL and utilities of nocturia in a real-world setting. Methods: Patient data were collected from two surveys: a nocturia-specific, cross-sectional survey of physicians and their patients (DSP), and a general UK population health survey (HSFE). Utilities (EQ-5D-5L), productivity (Work Productivity and Activity Index), and the impact of nocturia symptoms (Nocturia Impact Diary and Overactive Bladder Questionnaires) were assessed against the number of voids. A robust linear regression model with propensity score weights was used to control for confounding factors in estimating utilities. Results: Physician-recorded data were available from 8,738 patients across the US, Germany, Spain, France, and the UK; of these, 5,335 (61%) included patient-reported outcomes. In total, 6,302 controls were drawn from the two surveys and compared to 1,104 nocturia patients. Deterioration of HRQoL was associated with increasing number of night-time voids (pamp;lt;0.0001). In particular, significant differences were observed between 0-1 and 2 voids (pamp;lt;0.001). The regression model demonstrated that nocturia (amp;gt;= 2 per night) is associated with a modest but significant deterioration in utility of 0.0134 (pamp;lt;0.05). Limitations: The cause of nocturia is multifactorial and the mostly elderly patients may have several concomitant diseases. The authors tried to adjust for the most common ones, but there may be diseases or unknown relationships not included. Conclusions: Nocturia negatively affected HRQoL and patient utility. A clear effect is seen already at two voids per night. Every effort should, therefore, be made to reduce nocturia below the bother threshold of two voids per night.

  • 298.
    Andersson, Frieda
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences.
    Hjelm, Katarina
    Linköping University, Department of Social and Welfare Studies, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences.
    Patient safety in nursing homes in Sweden: nurses´views on safety and their role2017In: Journal of Health Services Research and Policy, ISSN 1355-8196, E-ISSN 1758-1060, Vol. 22, no 4, p. 204-210Article in journal (Refereed)
    Abstract [en]

    Objective: Knowledge about patient safety in nursing homes is limited. The aim of this study was to describe what patient safety means to nurses working in nursing homes for the elderly and how these nurses address patient safety. Method: Qualitative study of semi-structured interviews with 15 nurses aged 27-62 years. Qualitative content analysis was applied. Results: Nurses describe the meaning of patient safety in terms of proper care and treatment, and a sense of security. Based on nurses' description of patient safety, several factors were identified as prerequisites to achieve safe health care: competence; clear information transfer between health care organizations; continuity of care and appropriate environment. Barriers to patient safety were described as lack of sufficient resources; lack of communication and negative attitudes to incident reporting. To a great extent, nurses' work for patient safety consists of efforts to compensate for defects and ensure good health care in their daily work, since work with patient safety is not a management priority. Conclusion: Patient safety needs to be clarified and prioritized in nursing homes, and there is a need to understand nurses' role among other care givers and the need for shared routines among care givers

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  • 299.
    Andersson Hagiwara, Magnus
    et al.
    University of Boras, Sweden.
    Nilsson, Lena
    Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Anaesthesiology and Intensive Care in Norrköping. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Medical and Health Sciences, Division of Drug Research.
    Stromsoe, Anneli
    Malardalens Hogskola, Sweden.
    Axelsson, Christer
    University of Boras, Sweden.
    Kangstrom, Anna
    University of Boras, Sweden.
    Herlitz, Johan
    University of Boras, Sweden.
    Patient safety and patient assessment in pre-hospital care: a study protocol2016In: Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine, ISSN 1757-7241, E-ISSN 1757-7241, Vol. 24, no 14Article in journal (Refereed)
    Abstract [en]

    Background: Patient safety issues in pre-hospital care are poorly investigated. The aim of the planned study is to survey patient safety problems in pre-hospital care in Sweden. Methods/Design: The study is a retro-perspective structured medical record review based on the use of 11 screening criteria. Two instruments for structured medical record review are used: a trigger tool instrument designed for pre-hospital care and a newly development instrument designed to compare the pre-hospital assessment with the final hospital assessment. Three different ambulance organisations are participating in the study. Every month, one rater in each organisation randomly collects 30 medical records for review. With guidance from the review instrument, he/she independently reviews the record. Every month, the review team meet for a discussion of problematic reviews. The results will be analysed with descriptive statistics and logistic regression. Discussion: The findings will make an important contribution to knowledge about patient safety issues in prehospital care.

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  • 300.
    Andersson, Henrik
    et al.
    Linköping University, Faculty of Medicine and Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Anaesthesiology and Intensive Care in Linköping. Linköping University, Department of Medical and Health Sciences, Division of Drug Research.
    Björnström-Karlsson, Karin
    Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Anaesthesiology and Intensive Care in Linköping. Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Eintrei, Christina
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Anaesthesiology and Intensive Care in Linköping.
    Sundqvist, Tommy
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Orexin A Phosphorylates the gamma-Aminobutyric Acid Type A Receptor beta(2) Subunit on a Serine Residue and Changes the Surface Expression of the Receptor in SH-SY5Y Cells Exposed to Propofol2015In: Journal of Neuroscience Research, ISSN 0360-4012, E-ISSN 1097-4547, Vol. 93, no 11, p. 1748-1755Article in journal (Refereed)
    Abstract [en]

    Propofol activates the gamma-aminobutyric acid type A receptor (GABA(A)R) and causes a reversible neurite retraction, leaving a thin, thread-like structure behind; it also reverses the transport of vesicles in rat cortical neurons. The awakening peptide orexin A (OA) inhibits this retraction via phospholipase D (PLD) and protein kinase CE (PKCE). The human SH-SY5Y cells express both GABA(A)Rs and orexin 1 and 2 receptors. These cells are used to examine the interaction between OA and the GABAAR. The effects of OA are studied with flow cytometry and immunoblotting. This study shows that OA stimulates phosphorylation on the serine residues of the GABA(A)R beta(2) subunit and that the phosphorylation is caused by the activation of PLD and PKCE. OA administration followed by propofol reduces the cell surface expression of the GABA(A)R, whereas propofol stimulation before OA increases the surface expression. The GABA(A)R beta(2) subunit is important for receptor recirculation, and the effect of OA on propofol-stimulated cells may be due to a disturbed recirculation of the GABA(A)R. (C) 2015 Wiley Periodicals, Inc.

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