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  • 5651.
    Zech, Wolf-Dieter
    et al.
    University of Bern, Switzerland.
    Schwendener, Nicole
    University of Bern, Switzerland.
    Persson, Anders
    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. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Warntjes, Marcel Jan Bertus
    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).
    Riva, Fabiano
    University of Bern, Switzerland.
    Schuster, Frederick
    University of Bern, Switzerland; Hospital and University of Bern, Switzerland.
    Jackowski, Christian
    University of Bern, Switzerland.
    Postmortem quantitative 1.5-T MRI for the differentiation and characterization of serous fluids, blood, CSF, and putrefied CSF2015In: International journal of legal medicine (Print), ISSN 0937-9827, E-ISSN 1437-1596, Vol. 129, no 5, p. 1127-1136Article in journal (Refereed)
    Abstract [en]

    The purpose of the present study was to investigate whether serous fluids, blood, cerebrospinal fluid (CSF), and putrefied CSF can be characterized and differentiated in synthetically calculated magnetic resonance (MR) images based on their quantitative T (1), T (2), and proton density (PD) values. Images from 55 postmortem short axis cardiac and 31 axial brain 1.5-T MR examinations were quantified using a quantification sequence. Serous fluids, fluid blood, sedimented blood, blood clots, CSF, and putrefied CSF were analyzed for their mean T (1), T (2), and PD values. Body core temperature was measured during the MRI scans. The fluid-specific quantitative values were related to the body core temperature. Equations to correct for temperature differences were generated. In a 3D plot as well as in statistical analysis, the quantitative T (1), T (2) and PD values of serous fluids, fluid blood, sedimented blood, blood clots, CSF, and putrefied CSF could be well differentiated from each other. The quantitative T (1) and T (2) values were temperature-dependent. Correction of quantitative values to a temperature of 37 A degrees C resulted in significantly better discrimination between all investigated fluid mediums. We conclude that postmortem 1.5-T MR quantification is feasible to discriminate between blood, serous fluids, CSF, and putrefied CSF. This finding provides a basis for the computer-aided diagnosis and detection of fluids and hemorrhages.

  • 5652.
    Zeidan, Youssef H.
    et al.
    Amer Univ Beirut, Lebanon.
    Habib, Joyce G.
    Fouad Khoury and Makassed Gen Hosp, Lebanon; Univ Libre Bruxelles, Belgium.
    Ameye, Lieveke
    Universite´Libre de Bruxelles, Brussels, Belgium.
    Paesmans, Marianne
    Universite´Libre de Bruxelles, Brussels, Belgium.
    de Azambuja, Evandro
    Univ Libre Bruxelles, Belgium.
    Gelber, Richard D.
    Harvard Med Sch, MA USA; Frontier Sci and Technol Res Fdn Inc, MA USA.
    Campbell, Ian
    Univ Auckland, New Zealand.
    Nordenskjöld, Bo
    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 Oncology.
    Gutierez, Jorge
    Clin Los Condes, Chile.
    Anderson, Michael
    Copenhagen Univ Hosp, Denmark; Danish Breast Canc Cooperat Grp, Denmark.
    Lluch, Ana
    Univ Valencia, Spain.
    Gnant, Michael
    Med Univ Vienna, Austria; Austrian Breast and Colorectal Canc Study Grp, Austria.
    Goldhirsch, Aron
    European Inst Oncol, Italy; Int Breast Canc Study Grp, Switzerland.
    Di Leo, Angelo
    Hosp Prato, Italy.
    Joseph, David J.
    Univ Western Australia, Australia; Edith Cowan Univ, Australia; Breast Canc Trials Australia and New Zealand, Australia.
    Crown, John
    St Vincents Univ Hosp, Ireland.
    Piccart-Gebhart, Martine
    Univ Libre Bruxelles, Belgium.
    Francis, Prudence A.
    Int Breast Canc Study Grp, Switzerland; Peter MacCallum Canc Ctr, Australia; Univ Melbourne, Australia; Univ Newcastle, Australia.
    Postmastectomy Radiation Therapy in Women with T1-T2 Tumors and 1 to 3 Positive Lymph Nodes: Analysis of the Breast International Group 02-98 Trial2018In: International Journal of Radiation Oncology, Biology, Physics, ISSN 0360-3016, E-ISSN 1879-355X, Vol. 101, no 2, p. 316-324Article in journal (Refereed)
    Abstract [en]

    Purpose: To analyze the impact of postmastectomy radiation therapy (PMRT) for patients with T1-T2 tumors and 1 to 3 positive lymph nodes enrolled on the Breast International Group (BIG) 02-98 trial. Methods and Materials: The BIG 02-98 trial randomized patients to receive adjuvant anthracycline with or without taxane chemotherapy. Delivery of PMRT was nonrandomized and performed according to institutional preferences. The present analysis was performed on participants with T1-T2 breast cancer and 1 to 3 positive lymph nodes who had undergone mastectomy and axillary nodal dissection. The primary objective of the present study was to examine the effect of PMRT on risk of locoregional recurrence (LRR), breast cancer-specific survival, and overall survival. Results: We identified 684 patients who met the inclusion criteria and were included in the analysis, of whom 337 (49%) had received PMRT. At 10 years, LRR risk was 2.5% in the PMRT group and 6.5% in the no-PMRT group (hazard ratio 0.29, 95% confidence interval 0.12-0.73; P=.005). Lower LRR after PMRT was noted for patients randomized to receive adjuvant chemotherapy with no taxane (10-year LRR: 3.4% vs 9.1%; P=.02). No significant differences in breast cancer-specific survival (84.3% vs 83.9%) or overall survival (81.7% vs 78.3%) were observed according to receipt of PMRT. Conclusion: Our analysis of the BIG02-98 trial shows excellent outcomes in women with T1-T2 tumors and 1 to 3 positive lymph nodes found in axillary dissection. Although PMRT improved LRR in this cohort, the number of events remained low at 10 years. In all groups, 10-year rates of LRR were relatively low compared with historical studies. As such, the use of PMRT in women with 1 to 3 positive nodes should be tailored to individual patient risks. (C) 2018 Elsevier Inc. All rights reserved.

  • 5653.
    Zeitooni, Mehrnaz
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Mäki-Torkko, Elina
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Stenfelt, Stefan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Binaural Hearing Ability With Bilateral Bone Conduction Stimulation in Subjects With Normal Hearing: Implications for Bone Conduction Hearing Aids.2016In: Ear and Hearing, ISSN 0196-0202, E-ISSN 1538-4667, Vol. 37, no 6, p. 690-702Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: The purpose of this study is to evaluate binaural hearing ability in adults with normal hearing when bone conduction (BC) stimulation is bilaterally applied at the bone conduction hearing aid (BCHA) implant position as well as at the audiometric position on the mastoid. The results with BC stimulation are compared with bilateral air conduction (AC) stimulation through earphones.

    DESIGN: Binaural hearing ability is investigated with tests of spatial release from masking and binaural intelligibility level difference using sentence material, binaural masking level difference with tonal chirp stimulation, and precedence effect using noise stimulus.

    RESULTS: In all tests, results with bilateral BC stimulation at the BCHA position illustrate an ability to extract binaural cues similar to BC stimulation at the mastoid position. The binaural benefit is overall greater with AC stimulation than BC stimulation at both positions. The binaural benefit for BC stimulation at the mastoid and BCHA position is approximately half in terms of decibels compared with AC stimulation in the speech based tests (spatial release from masking and binaural intelligibility level difference). For binaural masking level difference, the binaural benefit for the two BC positions with chirp signal phase inversion is approximately twice the benefit with inverted phase of the noise. The precedence effect results with BC stimulation at the mastoid and BCHA position are similar for low frequency noise stimulation but differ with high-frequency noise stimulation.

    CONCLUSIONS: The results confirm that binaural hearing processing with bilateral BC stimulation at the mastoid position is also present at the BCHA implant position. This indicates the ability for binaural hearing in patients with good cochlear function when using bilateral BCHAs.

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  • 5654.
    Zeka, Bleranda
    et al.
    Department of Neuroimmunology, Center for Brain Research, Medical University Vienna, Spitalgasse 4, A-1090, Vienna, Austria.
    Hastermann, Maria
    Department of Neuroimmunology, Center for Brain Research, Medical University Vienna, Spitalgasse 4, A-1090, Vienna, Austria.
    Kaufmann, Nathalie
    Department of Neuroimmunology, Center for Brain Research, Medical University Vienna, Spitalgasse 4, A-1090, Vienna, Austria.
    Schanda, Kathrin
    Clinical Department of Neurology, Innsbruck Medical University, Innsbruck, Austria.
    Pende, Marko
    Medical University Vienna, Section for Bioelectronics, Center for Brain Research, Vienna, Austria.
    Misu, Tatsuro
    Department of Neurology, Tohoku University Graduate School of Medicine, Sendai, Japan.
    Rommer, Paulus
    Department of Neurology, Medical University Vienna, Wien, Austria.
    Fujihara, Kazuo
    Department of Neurology, Tohoku University Graduate School of Medicine, Sendai, Japan.
    Nakashima, Ichiro
    Department of Neurology, Tohoku University Graduate School of Medicine, Sendai, Japan.
    Dahle, Charlotte
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Leutmezer, Fritz
    Department of Neurology, Medical University Vienna, Wien, Austria.
    Reindl, Markus
    Clinical Department of Neurology, Innsbruck Medical University, Innsbruck, Austria.
    Lassmann, Hans
    Department of Neuroimmunology, Center for Brain Research, Medical University Vienna, Spitalgasse 4, A-1090, Vienna, Austria.
    Bradl, Monika
    Department of Neuroimmunology, Center for Brain Research, Medical University Vienna, Spitalgasse 4, A-1090, Vienna, Austria.
    Aquaporin 4-specific T cells and NMO-IgG cause primary retinal damage in experimental NMO/SD.2016In: Acta neuropathologica communications, E-ISSN 2051-5960, Vol. 4, no 1, article id 82Article in journal (Refereed)
    Abstract [en]

    Neuromyelitis optica/spectrum disorder (NMO/SD) is a severe, inflammatory disease of the central nervous system (CNS). In the majority of patients, it is associated with the presence of pathogenic serum autoantibodies (the so-called NMO-IgGs) directed against the water channel aquaporin 4 (AQP4), and with the formation of large, astrocyte-destructive lesions in spinal cord and optic nerves. A large number of recent studies using optical coherence tomography (OCT) demonstrated that damage to optic nerves in NMO/SD is also associated with retinal injury, as evidenced by retinal nerve fiber layer (RNFL) thinning and microcystic inner nuclear layer abnormalities. These studies concluded that retinal injury in NMO/SD patients results from secondary neurodegeneration triggered by optic neuritis.However, the eye also contains cells expressing AQP4, i.e., Müller cells and astrocytes in the retina, epithelial cells of the ciliary body, and epithelial cells of the iris, which raised the question whether the eye can also be a primary target in NMO/SD. Here, we addressed this point in experimental NMO/SD (ENMO) induced in Lewis rat by transfer of AQP4268-285-specific T cells and NMO-IgG.We show that these animals show retinitis and subsequent dysfunction/damage of retinal axons and neurons, and that this pathology occurs independently of the action of NMO-IgG. We further show that in the retinae of ENMO animals Müller cell side branches lose AQP4 reactivity, while retinal astrocytes and Müller cell processes in the RNFL/ganglionic cell layers are spared. These changes only occur in the presence of both AQP4268-285-specific T cells and NMO-IgG.Cumulatively, our data show that damage to retinal cells can be a primary event in NMO/SD.

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  • 5655.
    Zekveld, Adriana
    et al.
    Linköping University, Department of Behavioural Sciences and Learning. Linköping University, The Swedish Institute for Disability Research. Linköping University, Faculty of Arts and Sciences. Vrije Univ Amsterdam Med Ctr, Netherlands.
    Koelewijn, Thomas
    Vrije Univ Amsterdam Med Ctr, Netherlands.
    Kramer, Sophia E.
    Vrije Univ Amsterdam Med Ctr, Netherlands.
    The Pupil Dilation Response to Auditory Stimuli: Current State of Knowledge2018In: TRENDS IN HEARING, ISSN 2331-2165, Vol. 22, article id 2331216518777174Article, review/survey (Refereed)
    Abstract [en]

    The measurement of cognitive resource allocation during listening, or listening effort, provides valuable insight in the factors influencing auditory processing. In recent years, many studies inside and outside the field of hearing science have measured the pupil response evoked by auditory stimuli. The aim of the current review was to provide an exhaustive overview of these studies. The 146 studies included in this review originated from multiple domains, including hearing science and linguistics, but the review also covers research into motivation, memory, and emotion. The present review provides a unique overview of these studies and is organized according to the components of the Framework for Understanding Effortful Listening. A summary table presents the sample characteristics, an outline of the study design, stimuli, the pupil parameters analyzed, and the main findings of each study. The results indicate that the pupil response is sensitive to various task manipulations as well as interindividual differences. Many of the findings have been replicated. Frequent interactions between the independent factors affecting the pupil response have been reported, which indicates complex processes underlying cognitive resource allocation. This complexity should be taken into account in future studies that should focus more on interindividual differences, also including older participants. This review facilitates the careful design of new studies by indicating the factors that should be controlled for. In conclusion, measuring the pupil dilation response to auditory stimuli has been demonstrated to be sensitive method applicable to numerous research questions. The sensitivity of the measure calls for carefully designed stimuli.

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  • 5656.
    Zeng, Veronica Y.
    et al.
    Ferring Pharmaceut AS, Denmark; AstraZeneca Ltd, Singapore.
    Milligan, Gary
    Adelphi Real World, England.
    Piercy, James
    Adelphi Real World, England.
    Anderson, Peter
    Adelphi Real World, England.
    Andersson, Fredrik L.
    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.
    Impact of nocturia on patients health-related quality of life and healthcare resource utilisation compared with OAB and BPH: Results from an observational survey in European and American patientsIn: International journal of clinical practice (Esher), ISSN 1368-5031, E-ISSN 1742-1241, article id e13408Article in journal (Refereed)
    Abstract [en]

    Objective To evaluate the impact of nocturia on patients quality of life and healthcare resource utilisation (HRU) compared with overactive bladder (OAB) and benign prostatic hyperplasia (BPH). Methods Data were drawn from a multinational (France, Germany, Spain, UK and US) survey of physician and patient-reported outcomes. The patient groups of interests were those diagnosed with only nocturia, with only OAB, and with only BPH. Health-related quality of life (HRQoL) and productivity measures were derived from the EuroQoL-5D, OAB-q and the Work Productivity and Activity Impairment Questionnaire (WPAI). Measures of HRU included lower urinary tract symptoms (LUTS)-relevant surgeries, hospitalisations, current use of pads and related physician visits. Bivariate and multivariate regression analyses were used to evaluate associations between HRQoL/HRU/Productivity and nocturia status. Multivariate analysis was used to address any potential confounding factors among the groups, ie age, gender, body mass index (BMI), ethnicity and comorbidities. Results A total of 3552 patients were identified including 358 nocturia patients, 1415 OAB patients and 1779 BPH patients. The mean age of the nocturia patients was 61.2 years with a mean BMI of 27.3. About 60.6% were women, 87.2% were Caucasian, and their most common comorbidities included depression, hypertension and diabetes. In terms of impact, nocturia patients were significantly worse off than OAB patients in their HRQoL. There was no significant difference regarding HRU and productivity measurement. Nocturia patients also presented with significantly worse HRQoL and lower productivity compared with BPH patients. Nocturia patients also had more physician visits. Conclusions Nocturia should be emphasised as a standalone LUTS disease with substantial patient impact. Compared with OAB and/or BPH, nocturia patients presented with a significant reduction on patients quality of life, reduced work productivity and increased utilisation of healthcare resources.

  • 5657.
    Zetterling, Maria
    et al.
    Uppsala University, Sweden; Uppsala University Hospital, Sweden.
    Roodakker, Kenney R.
    Uppsala University, Sweden.
    Ghaderi Berntsson, Shala
    Uppsala University, Sweden; University of Uppsala Hospital, Sweden.
    Edqvist, Per-Henrik
    Uppsala University, Sweden.
    Latini, Francesco
    Uppsala University, Sweden.
    Landtblom, Anne-Marie
    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 Neurology. Linköping University, Center for Medical Image Science and Visualization (CMIV). Uppsala University, Sweden; University of Uppsala Hospital, Sweden.
    Ponten, Fredrik
    Uppsala University, Sweden.
    Alafuzoff, Irina
    Uppsala University, Sweden; University of Uppsala Hospital, Sweden.
    Larsson, Elna-Marie
    Uppsala University, Sweden; University of Uppsala Hospital, Sweden.
    Smits, Anja
    Uppsala University, Sweden; University of Uppsala Hospital, Sweden; Danish Epilepsy Centre, Denmark.
    Extension of diffuse low-grade gliomas beyond radiological borders as shown by the coregistration of histopathological and magnetic resonance imaging data2016In: Journal of Neurosurgery, ISSN 0022-3085, E-ISSN 1933-0693, Vol. 125, no 5, p. 1155-1166Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE Magnetic resonance imaging tends to underestimate the extent of diffuse low-grade gliomas (DLGGs). With the aim of studying the presence of tumor cells outside the radiological border, the authors developed a method of correlating MRI findings with histological data in patients with suspected DLGGs in whom en bloc resections were performed. METHODS Five patients with suspected DLGG suitable for en bloc resection were recruited from an ongoing prospective study. Sections of the entire tumor were immunostained with antibodies against mutated IDH1 protein (IDH1-R132H). Magnetic resonance images were coregistered with corresponding IDH1 images. The growth pattern of tumor cells in white and gray matter was assessed in comparison with signal changes on corresponding MRI slices. RESULTS Neuropathological assessment revealed DLGG in 4 patients and progression to WHO Grade III glioma in 1 patient. The tumor core consisted of a high density of IDH1-R132H positive tumor cells and was located in both gray and white matter. Tumor cells infiltrated along the peripheral fibers of the white matter tracts. In all cases, tumor cells were found outside the radiological tumor border delineated on T2-FLAIR MRI sequences. CONCLUSIONS The authors present a new method for the coregistration of histological and radiological characteristics of en bloc removed infiltrative brain tumors that discloses tumor invasion at the radiological tumor borders. This technique can be applied to evaluate the sensitivity of alternative imaging methods to detect scattered tumor cells at tumor borders. Accurate methods for detection of infiltrative tumor cells will improve the possibility of performing radical tumor resection. In future studies, the method could also be used for in vivo studies of tumor invasion.

  • 5658.
    Zetterlund, Eva-Lena
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Green, Henrik
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Oscarsson, Anna
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Anaesthesiology and Intensive Care in Norrköping. Linköping University, Department of Medical and Health Sciences, Division of Drug Research.
    Vikingsson, Svante
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Vrethem, Magnus
    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 Neurology.
    Lindholm, Maj-Lis
    Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Anaesthesiology and Intensive Care in Linköping. Kalmar Hospital, Sweden.
    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.
    Determination of loss of consciousness: a comparison of clinical assessment, bispectral index and electroencephalogram: An observational study2016In: European Journal of Anaesthesiology, ISSN 0265-0215, E-ISSN 1365-2346, Vol. 33, no 12, p. 922-928Article in journal (Refereed)
    Abstract [en]

    BACKGROUNDComputer-processed algorithms of encephalographic signals are widely used to assess the depth of anaesthesia. However, data indicate that the bispectral index (BIS), a processed electroencephalography monitoring system, may not be reliable for assessing the depth of anaesthesia.OBJECTIVEThe aim of this study was to evaluate the ability of the BIS monitoring system to assess changes in the level of unconsciousness, specifically during the transition from consciousness to unconsciousness, in patients undergoing total intravenous anaesthesia with propofol. We compared BIS with the electroencephalogram (EEG), and clinical loss of consciousness (LOC) defined as loss of verbal commands and eyelash reflex.DESIGNThis was an observational cohort study.SETTINGUniversity Hospital Linkoping, University Hospital orebro, Finspang Hospital and Kalmar Hospital, Sweden from October 2011 to April 2013.PATIENTSA total of 35 ASA I patients aged 18 to 49 years were recruited.INTERVENTIONSThe patients underwent total intravenous anaesthesia with propofol and remifentanil for elective day-case surgery. Changes in clinical levels of consciousness were assessed by BIS and compared with assessment of stage 3 neurophysiological activity using the EEG. The plasma concentrations of propofol were measured at clinical LOC and 20 and 30min after LOC.MAIN OUTCOME MEASURESThe primary outcome was measurement of BIS, EEG and clinical LOC.RESULTSThe median BIS value at clinical LOC was 38 (IQR 30 to 43), and the BIS values varied greatly between patients. There was no correlation between BIS values and EEG stages at clinical LOC (r=-0.1, P=0.064). Propofol concentration reached a steady state within 20min.CONCLUSIONThere was no statistically significant correlation between BIS and EEG at clinical LOC. BIS monitoring may not be a reliable method for determining LOC.CLINICAL TRIALS REGISTRYThis trial was not registered because registration was not mandatory at the time of the trial.

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  • 5659.
    Zetterqvist, Ann
    et al.
    University of Gothenburg, Sweden.
    Aronsson, Patrik
    University of Gothenburg, Sweden.
    Hägg, Staffan
    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.
    Kjellgren, Karin
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences.
    Reis, Margareta
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Tobin, Gunnar
    University of Gothenburg, Sweden.
    Booth, Shirley
    University of Gothenburg, Sweden; University of Witwatersrand, South Africa.
    On the pedagogy of pharmacological communication: a study of final semester health science students2015In: BMC Medical Education, ISSN 1472-6920, E-ISSN 1472-6920, Vol. 15Article in journal (Refereed)
    Abstract [en]

    Background: There is a need to improve design in educational programmes for the health sciences in general and in pharmacology specifically. The objective of this study was to investigate and problematize pharmacological communication in educational programmes for the health sciences. Methods: An interview study was carried out where final semester students from programmes for the medical, nursing and specialist nursing in primary health care professions were asked to discuss the pharmacological aspects of two written case descriptions of the kind they would meet in their everyday work. The study focused on the communication they envisaged taking place on the concerns the patients were voicing, in terms of two features: how communication would take place and what would be the content of the communication. A phenomenographic research approach was used. Results: The results are presented as outcome spaces, sets of categories that describe the variation of ways in which the students voiced their understanding of communication in the two case descriptions and showed the qualitatively distinct ways in which the features of communication were experienced. Conclusions: The results offer a base of understanding the students perspectives on communication that they will take with them into their professional lives. We indicate that there is room for strengthening communication skills in the field of pharmacology, integrating them into programmes of education, by more widely implementing a problem-based, a case-oriented or role-playing pedagogy where final year students work across specialisations and there is a deliberate effort to evoke and assess advanced conceptions and skills.

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  • 5660.
    Zetterqvist, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. 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.
    Nonsuicidal Self-Injury in Adolescents: Characterization of the Disorder and the Issue of Distress and Impairment.2017In: Journal of Suicide and Life-threatening Behaviour, ISSN 0363-0234, E-ISSN 1943-278X, Vol. 47, no 3, p. 321-335Article in journal (Refereed)
    Abstract [en]

    Nonsuicidal self-injury disorder (NSSID) is a condition in need of further study to assess the validity of the potential diagnosis and its suggested criteria. This study examined the NSSID diagnosis and investigated the distress/impairment criterion by comparing community adolescents who met all criteria for NSSID (n = 186) to adolescents with five or more nonsuicidal self-injury (NSSI) episodes (n = 314), and to a group of adolescents who met all criteria but negated that their NSSI caused them any distress or impairment, thus failing to meet criterion E (n = 29). The NSSID group delimited from the ≥ 5 NSSI group by reporting significantly more frequent and severe self-injurious thoughts and behaviors, as well as having more experiences of negative life events and higher levels of trauma symptoms. There were also some differences between the NSSID group and adolescents without distress/impairment, which together contribute valuable information on the potential NSSID diagnosis, as well as the discussion of criterion E.

  • 5661.
    Zetterqvist, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Child and Adolescent Psychiatry in Linköping. RÖ.
    The DSM-5 diagnosis of nonsuicidal self-injury disorder: A review of the empirical literature2015In: Child and Adolescent Psychiatry and Mental Health, ISSN 1753-2000, E-ISSN 1753-2000, Vol. 9, no 31, p. 1-13Article, review/survey (Refereed)
    Abstract [en]

    With the presentation of nonsuicidal self-injury disorder (NSSID) criteria in the fifth version of the Statistical and Diagnostic Manual of Mental Disorders (DSM-5), empirical studies have emerged where the criteria have been operationalized on samples of children, adolescents and young adults. Since NSSID is a condition in need of further study, empirical data are crucial at this stage in order to gather information on the suggested criteria concerning prevalence rates, characteristics, clinical correlates and potential independence of the disorder. A review was conducted based on published peer-reviewed empirical studies of the DSM-5 NSSID criteria up to May 16, 2015. When the DSM-5 criteria were operationalized on both clinical and community samples, a sample of individuals was identified that had more general psychopathology and impairment than clinical controls as well as those with NSSI not meeting criteria for NSSID. Across all studies interpersonal difficulties or negative state preceding NSSI was highly endorsed by participants, while the distress or impairment criterion tended to have a lower endorsement. Results showed preliminary support for a distinct and independent NSSID diagnosis, but additional empirical data are needed with direct and structured assessment of the final DSM-5 criteria in order to reliably assess and validate a potential diagnosis of NSSID.

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  • 5662.
    Zetterqvist, Maria
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. 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.
    Hanell, H. Erneroth
    Stockholm City Council, Sweden.
    Wadsby, Marie
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Cocozza, Madeleine
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Gustafsson, Per
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. 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.
    Validation of the Systemic Clinical Outcome and Routine Evaluation (SCORE-15) self-report questionnaire: index of family functioning and change in Swedish families2020In: Journal of Family Therapy, ISSN 0163-4445, E-ISSN 1467-6427, Vol. 42, no 1, p. 129-148Article in journal (Refereed)
    Abstract [en]

    Instruments for evaluating the progress and outcome of systemic therapeutic treatments in clinical practice need to be easily administered and have sound psychometric properties. The Systemic Clinical Outcome and Routine Evaluation, 15-item version (SCORE-15), is a self-report instrument that measures aspects of family functioning. This study investigates the psychometric qualities of a Swedish version of SCORE-15. Seventy Swedish families with healthy children and 159 families with children with psychiatric or behavioural problems were included in the study, resulting in a total of 397 individuals. Results showed that SCORE-15 differentiated clinical from non-clinical families with acceptable psychometric properties for test-retest, internal consistency, convergent and construct validity, as well as sensitivity to change for the clinical sample. The three-factor solution of strengths, difficulties and communication was tested. Results imply preliminary psychometric support for the use of the Swedish version of SCORE-15 to evaluate progress and outcome in clinical practice. Practitioner points SCORE-15 is an easily administered questionnaire suitable for use in clinical practice to evaluate systemic therapeutic progress and outcome The Swedish version of SCORE-15 has acceptable psychometric properties

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  • 5663.
    Zetterqvist, Maria
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Child and Adolescent Psychiatry. Linköping University, Faculty of Health Sciences.
    Lundh, Lars-Gunnar
    Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Child and Adolescent Psychiatry in Linköping.
    Dahlström, Örjan
    Linköping University, Department of Behavioural Sciences and Learning, Disability Research. Linköping University, Faculty of Arts and Sciences.
    Svedin, Carl Göran
    Linköping University, Department of Clinical and Experimental Medicine, Child and Adolescent Psychiatry. Linköping University, Faculty of Health Sciences.
    Prevalence and Function of Non-Suicidal Self-Injury (NSSI) in a Community Sample of Adolescents, Using Suggested DSM-5 Criteria for a Potential NSSI Disorder2013In: Journal of Abnormal Child Psychology, ISSN 0091-0627, E-ISSN 1573-2835, Vol. 41, no 5, p. 759-773Article in journal (Refereed)
    Abstract [en]

    Previous prevalence rates of non-suicidal self-injury (NSSI) in adolescents have varied considerably. In the present cross-sectional study, prevalence rates, characteristics and functions of NSSI were assessed in a large randomized community sample consisting of 3,060 (50.5 % female) Swedish adolescents aged 15-17 years. The suggested criteria for NSSI disorder in the Diagnostic and Statistical Manual of Mental Disorders, 5th edition, (DSM-5) were used to assess prevalence rates with the aim of arriving at a more precise estimate. Out of the whole sample, 1,088 (35.6 %) adolescents (56.2 % female) reported at least one episode of NSSI during the last year, of which 205 (6.7 %) met suggested DSM-5 criteria for a potential NSSI disorder diagnosis. The NSSI disorder diagnosis was significantly more common in girls (11.1 % vs. 2.3 %, χ (2) (1, N = 3046) = 94.08, p < 0.001, cOR = 5.43, 95 % CI [3.73, 7.90]). The NSSI disorder group consisted of significantly more smokers and drug users compared to adolescents with NSSI that did not meet DSM-5 criteria for NSSI disorder, and also differed concerning demographic variables. A confirmatory factor analysis (CFA) was conducted on reported functions of NSSI, with the aim of validating Nock and Prinstein's (Journal of Consulting and Clinical Psychology 72:885-890, 2004, Journal of Abnormal Psychology 114:140-146, 2005) four-factor model on a Swedish community sample, resulting in a close to acceptable fit. A two-factor model (social and automatic reinforcement) resulted in a slightly better fit. The most frequently reported factors were positive and negative automatic reinforcement. A majority of functions were significantly more often reported by girls than boys. The implications of the suggested DSM-5 criteria and reported functions are discussed.

  • 5664.
    Zetterqvist, Maria
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Child and Adolescent Psychiatry in Linköping.
    Lundh, Lars-Gunnar
    Department of Psychology, Lund University, Sweden.
    Svedin, Carl Göran
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Child and Adolescent Psychiatry in Linköping.
    A cross-sectional study of adolescent non-suicidal self-injury: support for a specific distress-function relationship2014In: Child and Adolescent Psychiatry and Mental Health, ISSN 1753-2000, E-ISSN 1753-2000, Vol. 8, no 23Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: This study has investigated the specific relationship between childhood adversities, individual trauma symptoms and the functions of non-suicidal self-injury (NSSI). The aim was to examine whether different self-reported adverse experiences and trauma symptoms predict the need to engage in NSSI, either to regulate emotions or to communicate with and influence others.

    METHOD: The participants were a community sample of 816 adolescents aged 15-17 years with NSSI. Hierarchical multiple regression was used, controlling for NSSI frequency and gender. The dependent variables were the automatic and social functions of NSSI, respectively. The predictors entered in the model were several different maltreatment and adversity experiences as well as individual trauma symptoms. Mediation analyses were also performed using the bootstrapping method with bias-corrected confidence estimates.

    RESULTS: Frequency of NSSI, gender (female), emotional abuse, prolonged illness or handicap during upbringing and symptoms of depression uniquely predicted the automatic functions of NSSI in the final regression model, but not the social functions. Symptoms of anxiety uniquely predicted social but not automatic functions. Having experienced physical abuse, having made a suicide attempt and symptoms of dissociation were significant predictors in both final models. The model for automatic functions explained more of the variance (62%) than the social model (28%). The relationship between childhood emotional, physical and sexual abuse and performing NSSI for automatic reasons was mediated by symptoms of depression and dissociation. The relationship between physical abuse and the social functions of NSSI was mediated by symptoms of anxiety and dissociation.

    CONCLUSIONS: It is important to understand the specific context in which NSSI has developed and is maintained. Experiences of emotional abuse and symptoms of depression could guide clinical work in the direction of emotion regulation skills since in this study these variables were uniquely associated with the need to engage in NSSI to regulate emotions, to self-punish or to generate feelings. The presence of physical abuse, a suicide attempt and symptoms of dissociation could alert clinicians to a broad treatment approach since they were associated with performing NSSI to regulate both social and automatic experiences.

  • 5665.
    Zetterqvist, Maria
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. 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.
    Perini, Irene
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Mayo, Leah
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Gustafsson, Per
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. 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.
    Nonsuicidal Self-Injury Disorder in Adolescents: Clinical Utility of the Diagnosis Using the Clinical Assessment of Nonsuicidal Self-Injury Disorder Index2020In: Frontiers in Psychiatry, ISSN 1664-0640, E-ISSN 1664-0640, Vol. 11, article id 8Article in journal (Refereed)
    Abstract [en]

    Nonsuicidal self-injury disorder (NSSID) is a condition in need of further study, especially in adolescent and clinical populations where it is particularly prevalent and studies are limited. Twenty-nine clinical self-injuring adolescents were included in the study. The Clinical Assessment of Nonsuicidal Self-Injury Disorder Index (CANDI) was used to assess prevalence of NSSID. The NSSID diagnosis criteria were met by 62.1% of adolescents. The impairment or distress criterion was least often met. Criteria B and C (assessing reasons for NSSI and cognitions/emotions prior to NSSI) were confirmed by 96-100% of all participants. Adolescents with NSSI in this clinical sample had several comorbidities and high levels of psychopathology. NSSID occurred both in combination with and independently of borderline personality disorder traits as well as suicide plans and attempts. Those with NSSID had a significantly higher cutting frequency than those not meeting full NSSID criteria. Other NSSI characteristics, comorbidity, psychopathology, and trauma experiences did not differ between groups. CANDI was a feasible tool to assess NSSID in adolescents. It is important to use structured measures to assess the validity of the NSSID diagnosis across development in both community and clinical samples. The clinical utility of the NSSID diagnosis is discussed.

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  • 5666.
    Zetterqvist, Maria
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. 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.
    Svedin, Carl Göran
    Linköping University, Department of Clinical and Experimental Medicine, Barnafrid. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Child and Adolescent Psychiatry in Linköping.
    Fredlund, Cecilia
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Psychiatry.
    Priebe, Gisela
    Linköping University, Department of Clinical and Experimental Medicine, Barnafrid. Linköping University, Faculty of Medicine and Health Sciences. Lund Univ, Sweden.
    Wadsby, Marie
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Jonsson, Linda
    Linköping University, Department of Clinical and Experimental Medicine, Barnafrid. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Child and Adolescent Psychiatry in Linköping.
    Self-reported nonsuicidal self-injury (NSSI) and sex as self-injury (SASI): Relationship to abuse, risk behaviors, trauma symptoms, self-esteem and attachment2018In: Psychiatry Research, ISSN 0165-1781, E-ISSN 1872-7123, Vol. 265, p. 309-316Article in journal (Refereed)
    Abstract [en]

    This study focuses on a conceptually unexplored behavior among adolescents who report deliberately using sex as a means of self-injury. In a large high school-based sample (n = 5743), adolescents who engaged in sex as self injury (SASI, n = 43) were compared to adolescents who reported direct nonsuicidal self-injury (NSSI, n = 933) and those who reported both NSSI and SASI (n = 82). Re.sults showed that significantly more adolescents with SASI had experience of penetrating sexual abuse, as well as more sexual partners compared to those with NSSI. The SASI group also had higher levels of self-reported trauma symptoms, such as dissociation, posttraumatic stress and sexual concerns compared to those with NSSI, suggesting a distinct relationship between sexual abuse, trauma symptoms and engaging in sex as self-injury. There was no difference between the SASI and NSSI groups regarding experiences of emotional and physical abuse, self-esteem, parental care or overprotection or symptoms of depression, anxiety and anger. Adolescents who engaged in both NSSI + SASI stood out as a more severe and burdened group, with more experience of abuse, risk behaviors and impaired psychosocial health. Adolescents with traumatic experiences such as sexual abuse need to be assessed for SASI and vice versa.

  • 5667.
    Zetterqvist, Vendela
    et al.
    Linköping University, The Swedish Institute for Disability Research. Linköping University, Department of Behavioural Sciences and Learning, Disability Research. Linköping University, Faculty of Educational Sciences.
    Andersson, Gerhard
    Linköping University, Department of Behavioural Sciences and Learning, Psychology. Linköping University, Faculty of Arts and Sciences.
    Kaldo, Viktor
    Karolinska Institutet, Stockholm.
    Leva med tinnitus2013 (ed. 1)Book (Other (popular science, discussion, etc.))
    Abstract [sv]

    Har du ett klingande, ringande, tjutande, brusande, surrande, visslande ljud i huvudet eller öronen som påverkar ditt dagliga liv? Ett stort antal personer i Sverige upplever att tinnitus inverkar på deras mående, sömn, koncentrationsförmåga och livskvalitet.Ljudet kan uppfattas störande i ett flertal situationer och ljudmiljöer såsom i tystnad, vid restaurangbesök eller vid samtal. Vissa upplever inte längre samma glädje i aktiviteter som de tidigare uppskattade. Andra känner en oro och frågar sig om deras tinnitus kommer att bli värre, eller om den är tecken på något allvarligt fel.Leva med tinnitus är en självhjälpsbok som bygger på material som arbetats fram och prövats med goda resultat under flera år av forskning och som tillvaratar den senaste utvecklingen inom tinnitusbehandling. Metoderna i boken är hämtade från kognitiv beteendeterapi (KBT) och acceptance and commitment therapy (ACT). Läsaren får arbeta med olika beprövade tekniker och tillägnar sig nya förhållningssätt. Syftet är att tinnitus inte längre ska behöva ta lika stor plats i den enskildes liv.

  • 5668.
    Zhang, Hong
    et al.
    University of Örebro, Sweden.
    Zhu, Zhen-Long
    Hebei Medical University, Peoples R China.
    Wang, Da-Wei
    Hebei Medical University, Peoples R China.
    Yang, Yan-Hong
    Hebei Medical University, Peoples R China.
    Wang, Hao
    Hebei Medical University, Peoples R China.
    Sun, Xiao-Feng
    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.
    Upregulation of nucleoporin 88 is associated with nodal metastasis and poor differentiation in oral squamous cell carcinoma2016In: International Journal of Clinical and Experimental Medicine, ISSN 1940-5901, E-ISSN 1940-5901, Vol. 9, no 5, p. 8399-8404Article in journal (Refereed)
    Abstract [en]

    Nucleoporin 88 (Nup 88) is a component of the nuclear pore complexes (NPCs) that mediates nucleocytoplasmic trafficking of macromolecules, Nup 88 has been reported to be up-regulated in a wide variety of malignancies. Studies show that overexpression of this antigen is associated with the development, agressiveness, differentiation and prognosis in some tumours. Since no study has been carried out in the relationship between the Nup 88 expression and clinicopathological features in the patients with oral squamous cell carcinoma (OSCC), this study aimed to determine Nup 88 expression in OSCC and its clinicopathological significance. Nup 88 expression was examined by immunohistochemistry in 20 normal oral mucosa specimens and 83 OSCC tissues. The frequency of positive Nup 88 expression was gradually increased from normal oral mucosa (10%) to primary OSCC (40%, P=0.012). The Nup 88 positive rate in OSCC patient with nodal metastasis was significantly higher than those without nodal metastasis (64% vs. 21%, P=0.000085). The frequency of positive Nup 88 expression was significantly different between worse and better differentiation (80 vs. 27%, P=0.000024). Nup 88 expression was not related to the patients gender, age, location and tumour size (Pamp;gt;0.05). In conclusion, Nup 88 may play an important role in tumorigenesis in oral squamous cell carcinoma. Upregulation of Nup 88 is associated with nodal metastasis and poor differentiation in oral squamous cell carcinoma.

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  • 5669.
    Zhang, Huan
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Gustafsson, Mika
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Nestor, Colm E
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Chung, Kian Fan
    Experimental Studies, National Heart and Lung Institute, Imperial College London, London, UK / NIHR Respiratory Biomedical Research Unit at the Royal Brompton NHS Foundation Trust and Imperial College London, London, UK; Royal Brompton NHS Fdn Trust, NIHR Resp Biomed Res Unit, London, England.
    Benson, Mikael
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Allergy Center. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Targeted omics and systems medicine: personalising care2014In: The Lancet Respiratory Medicine, ISSN 2213-2600, E-ISSN 2213-2619, Vol. 2, no 10, p. 785-787Article in journal (Other academic)
  • 5670.
    Zhang, Huan
    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. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Klareskog, Lars
    Karolinska Inst, Sweden.
    Matussek, Andreas
    Karolinska Univ Hosp Lab, Sweden.
    Pfister, Stefan M.
    Hopp Childrens Canc Ctr Heidelberg KiTZ, Germany; German Canc Res Ctr, Germany; German Canc Consortium DKTK, Germany; Heidelberg Univ Hosp, Germany.
    Benson, Mikael
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Editorial Material: Translating genomic medicine to the clinic: challenges and opportunities in GENOME MEDICINE, vol 11, issue , pp2019In: Genome Medicine, ISSN 1756-994X, E-ISSN 1756-994X, Vol. 11, article id 9Article in journal (Other academic)
    Abstract [en]

    Editorial summaryGenomic medicine has considerable potential to provide novel diagnostic and therapeutic solutions for patients who have molecularly complex diseases and who are not responding to existing therapies. To bridge the gap between genomic medicine and clinical practice, integration of various data types, resources, and joint international initiatives will be required.

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  • 5671.
    Zhang, Jiao
    et al.
    West China Hospital, Sichuan University, Chengdu, China.
    Zhou, Bin
    IWest China Hospital, Sichuan University, Chengdu, China.
    Liu, Yinghua
    DWest China Hospital, Sichuan University, Chengdu, China.
    Chen, Keling
    West China Hospital, Sichuan University, Chengdu, China.
    Bao, Pingqian
    West China Hospital, Sichuan University, Chengdu, China.
    Wang, Yi
    West China Hospital, Sichuan University, Chengdu, China.
    Wang, Jiaxiang
    First Affiliated Hospital of Zhengzhou University, Henan, China.
    Zhou, Zongguang
    West China Hospital, Sichuan University, Chengdu, China.
    Sun, Xiao-Feng
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology. nstitute of Digestive Surgery, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
    Li, Yuan
    West China Hospital, Sichuan University, Chengdu, China.
    Wnt inhibitory factor-1 functions as a tumor suppressor through modulating Wnt/β-catenin signaling in neuroblastoma2014In: Cancer Letters, ISSN 0304-3835, E-ISSN 1872-7980, Vol. 348, no 1–2, p. 12-19Article in journal (Refereed)
    Abstract [en]

    Neuroblastoma is the most common extracranial solid tumor in childhood and is associated with serious morbidity and mortality. The effective treatment of neuroblastoma remains one of the major challenges in pediatric oncology. The Wnt signaling pathway has been shown to play a significant role in the pathogenesis of adult and pediatric tumors. WIF-1 has been identified as an important Wnt antagonist which inhibits Wnt/β-catenin signaling by directly binding to Wnt proteins. However, the expression and function of WIF-1 in neuroblastoma remains unknown. The present study showed that WIF-1 was downregulated with high level promoter methylation in neuroblastoma cells, and was significantly upregulated after exposure to demethylating agent. This finding suggests that downregulation of WIF-1 was associated with its promoter methylation in neuroblastoma. To further study the potential function of WIF-1 in neuroblastoma, we constructed a plasmid that over-expressed WIF-1 and transfected the plasmid into one neuroblastoma cell line SK-N-SH. We found that restoration of WIF-1 inhibited the growth and proliferation of neuroblastoma cells in vitro. Morever, Wnt/β-catenin signaling activity and target genes expression were reduced by WIF-1 restoration. These results provide support that WIF-1 is downregulated and functions as a tumor suppressor by antagonizing Wnt/β-catenin signaling in neuroblastoma, suggesting a potential role as a therapeutic target in neuroblastoma.

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  • 5672.
    Zhang, Ming-Ran
    et al.
    Sichuan University, Peoples R China; Sichuan University, Peoples R China; Sichuan University, Peoples R China.
    Xie, Tian-Hang
    Sichuan University, Peoples R China.
    Chi, Jun-Lin
    Sichuan University, Peoples R China.
    Li, Yuan
    Sichuan University, Peoples R China.
    Yang, Lie
    Sichuan University, Peoples R China.
    Yu, Yong-Yang
    Sichuan University, Peoples R China.
    Sun, Xiao-Feng
    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. Sichuan University, Peoples R China.
    Zhou, Zong-Guang
    Sichuan University, Peoples R China.
    Prognostic role of the lymph node ratio in node positive colorectal cancer: a meta-analysis2016In: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 7, no 45, p. 72898-72907Article in journal (Refereed)
    Abstract [en]

    The lymph node ratio (LNR) (i. e. the number of metastatic lymph nodes divided by the number of totally resected lymph nodes) has recently emerged as an important prognostic factor in colorectal cancer (CRC). However, the tumor node metastasis (TNM) staging system for colorectal cancer does not consider it as a prognostic parameter. Therefore, we conducted a meta-analysis to evaluate the prognostic role of the LNR in node positive CRC. A systematic search was performed in PubMed, Embase and the Cochrane Library for relevant studies up to November 2015. As a result, a total of 75,838 node positive patients in 33 studies were included in this meta-analysis. Higher LNR was significantly associated with shorter overall survival (OS) (HR = 1.91; 95% CI 1.71-2.14; P = 0.0000) and disease free survival (DFS) (HR = 2.75; 95% CI: 2.14-3.53; P = 0.0000). Subgroup analysis showed similar results. Based on these results, LNR was an independent predictor of survival in colorectal cancer patients and should be considered as a parameter in future oncologic staging systems.

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  • 5673.
    Zhang, Xiaonan
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Karolinska Institute, Sweden.
    de Milito, Angelo
    Karolinska Institute, Sweden.
    Hagg Olofsson, Maria
    Karolinska Institute, Sweden.
    Gullbo, Joachim
    Uppsala University, Sweden.
    D´arcy, Padraig
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Karolinska Institute, Sweden.
    Linder, Stig
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Karolinska Institute, Sweden.
    Targeting Mitochondrial Function to Treat Quiescent Tumor Cells in Solid Tumors2015In: International Journal of Molecular Sciences, ISSN 1422-0067, E-ISSN 1422-0067, Vol. 16, no 11, p. 27313-27326Article, review/survey (Refereed)
    Abstract [en]

    The disorganized nature of tumor vasculature results in the generation of microenvironments characterized by nutrient starvation, hypoxia and accumulation of acidic metabolites. Tumor cell populations in such areas are often slowly proliferating and thus refractory to chemotherapeutical drugs that are dependent on an active cell cycle. There is an urgent need for alternative therapeutic interventions that circumvent growth dependency. The screening of drug libraries using multicellular tumor spheroids (MCTS) or glucose-starved tumor cells has led to the identification of several compounds with promising therapeutic potential and that display activity on quiescent tumor cells. Interestingly, a common theme of these drug screens is the recurrent identification of agents that affect mitochondrial function. Such data suggest that, contrary to the classical Warburg view, tumor cells in nutritionally-compromised microenvironments are dependent on mitochondrial function for energy metabolism and survival. These findings suggest that mitochondria may represent an Achilles heel for the survival of slowly-proliferating tumor cells and suggest strategies for the development of therapy to target these cell populations.

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  • 5674.
    Zhang, Xueli
    et al.
    Orebro Univ, Sweden; Soochow Univ, Peoples R China.
    Sun, Xiao-Feng
    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 Oncology.
    Shen, Bairong
    Soochow Univ, Peoples R China.
    Zhang, Hong
    Orebro Univ, Sweden.
    Potential Applications of DNA, RNA and Protein Biomarkers in Diagnosis, Therapy and Prognosis for Colorectal Cancer: A Study from Databases to AI-Assisted Verification2019In: Cancers, ISSN 2072-6694, Vol. 11, no 2, article id 172Article in journal (Refereed)
    Abstract [en]

    In order to find out the most valuable biomarkers and pathways for diagnosis, therapy and prognosis in colorectal cancer (CRC) we have collected the published CRC biomarkers and established a CRC biomarker database (CBD: http://sysbio.suda.edu.cn/CBD/index.html). In this study, we analysed the single and multiple DNA, RNA and protein biomarkers as well as their positions in cancer related pathways and protein-protein interaction (PPI) networks to describe their potential applications in diagnosis, therapy and prognosis. CRC biomarkers were collected from the CBD. The RNA and protein biomarkers were matched to their corresponding DNAs by the miRDB database and the PubMed Gene database, respectively. The PPI networks were used to investigate the relationships between protein biomarkers and further detect the multiple biomarkers. The Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway enrichment analysis and Gene Ontology (GO) annotation were used to analyse biological functions of the biomarkers. AI classification techniques were utilized to further verify the significances of the multiple biomarkers in diagnosis and prognosis for CRC. We showed that a large number of the DNA, RNA and protein biomarkers were associated with the diagnosis, therapy and prognosis in various degrees in the CRC biomarker networks. The CRC biomarkers were closely related to the CRC initiation and progression. Moreover, the biomarkers played critical roles in cellular proliferation, apoptosis and angiogenesis and they were involved in Ras, p53 and PI3K pathways. There were overlaps among the DNA, RNA and protein biomarkers. AI classification verifications showed that the combined multiple protein biomarkers played important roles to accurate early diagnosis and predict outcome for CRC. There were several single and multiple CRC protein biomarkers which were associated with diagnosis, therapy and prognosis in CRC. Further, AI-assisted analysis revealed that multiple biomarkers had potential applications for diagnosis and prognosis in CRC.

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  • 5675.
    Zhang, Xueli
    et al.
    Orebro Univ, Sweden; Soochow Univ, Peoples R China.
    Zhang, Hong
    Orebro Univ, Sweden.
    Shen, Bairong
    Soochow Univ, Peoples R China.
    Sun, Xiao-Feng
    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 Oncology.
    Chromogranin-A Expression as a Novel Biomarker for Early Diagnosis of Colon Cancer Patients2019In: International Journal of Molecular Sciences, ISSN 1422-0067, E-ISSN 1422-0067, Vol. 20, no 12, article id 2919Article in journal (Refereed)
    Abstract [en]

    Colon cancer is one of the major causes of cancer death worldwide. The five-year survival rate for the early-stage patients is more than 90%, and only around 10% for the later stages. Moreover, half of the colon cancer patients have been clinically diagnosed at the later stages. It is; therefore, of importance to enhance the ability for the early diagnosis of colon cancer. Taking advantages from our previous studies, there are several potential biomarkers which have been associated with the early diagnosis of the colon cancer. In order to investigate these early diagnostic biomarkers for colon cancer, human chromogranin-A (CHGA) was further analyzed among the most powerful diagnostic biomarkers. In this study, we used a logistic regression-based meta-analysis to clarify associations of CHGA expression with colon cancer diagnosis. Both healthy populations and the normal mucosa from the colon cancer patients were selected as the double normal controls. The results showed decreased expression of CHGA in the early stages of colon cancer as compared to the normal controls. The decline of CHGA expression in the early stages of colon cancer is probably a new diagnostic biomarker for colon cancer diagnosis with high predicting possibility and verification performance. We have also compared the diagnostic powers of CHGA expression with the typical oncogene KRAS, classic tumor suppressor TP53, and well-known cellular proliferation index MKI67, and the CHGA showed stronger ability to predict early diagnosis for colon cancer than these other cancer biomarkers. In the protein-protein interaction (PPI) network, CHGA was revealed to share some common pathways with KRAS and TP53. CHGA might be considered as a novel, promising, and powerful biomarker for early diagnosis of colon cancer.

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  • 5676.
    Zhang, Yin
    et al.
    Karolinska Institute, Sweden; Shandong University, Peoples R China; Shandong University, Peoples R China.
    Yang, Yunlong
    Karolinska Institute, Sweden.
    Hosaka, Kayoko
    Karolinska Institute, Sweden.
    Huang, Guichun
    Karolinska Institute, Sweden.
    Zang, Jingwu
    BioSciKin Biopharma, Peoples R China.
    Chen, Fang
    Zhejiang Chinese Medical University, Peoples R China.
    Zhang, Yun
    Karolinska Institute, Sweden; Shandong University, Peoples R China; Shandong University, Peoples R China.
    Samani, Nilesh J.
    University of Leicester, England; Glenfield Gen Hospital, England.
    Cao, Yihai
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Karolinska Institute, Sweden; University of Leicester, England; Glenfield Gen Hospital, England; Second Hospital Wuxi, Peoples R China.
    Endocrine vasculatures are preferable targets of an antitumor ineffective low dose of anti-VEGF therapy2016In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 113, no 15, p. 4158-4163Article in journal (Refereed)
    Abstract [en]

    Anti-VEGF-based antiangiogenic drugs are designed to block tumor angiogenesis for treatment of cancer patients. However, anti-VEGF drugs produce off-tumor target effects on multiple tissues and organs and cause broad adverse effects. Here, we show that vasculatures in endocrine organs were more sensitive to anti-VEGF treatment than tumor vasculatures. In thyroid, adrenal glands, and pancreatic islets, systemic treatment with low doses of an anti-VEGF neutralizing antibody caused marked vascular regression, whereas tumor vessels remained unaffected. Additionally, a low dose of VEGF blockade significantly inhibited the formation of thyroid vascular fenestrae, leaving tumor vascular structures unchanged. Along with vascular structural changes, the low dose of VEGF blockade inhibited vascular perfusion and permeability in thyroid, but not in tumors. Prolonged treatment with the low-dose VEGF blockade caused hypertension and significantly decreased circulating levels of thyroid hormone free-T3 and -T4, leading to functional impairment of thyroid. These findings show that the fenestrated microvasculatures in endocrine organs are more sensitive than tumor vasculatures in response to systemic anti-VEGF drugs. Thus, our data support the notion that clinically nonbeneficial treatments with anti-VEGF drugs could potentially cause adverse effects.

  • 5677.
    Zhao, Chunyan
    et al.
    Department of Biosciences and Nutrition, Novum, Karolinska Institute, Huddinge, Sweden.
    Qiao, Yichun
    Department of Biosciences and Nutrition, Novum, Karolinska Institute, Huddinge, Sweden.
    Jonsson, Philip
    University of Houston, Texas, USA.
    Wang, Jian
    Karolinska Institute, Stockholm, Sweden .
    Xu, Li
    Department of Biosciences and Nutrition, Novum, Karolinska Institute, Huddinge, Sweden.
    Rouhi, Pegah
    Karolinska Institute, Stockholm, Sweden .
    Sinha, Indranil
    Department of Biosciences and Nutrition, Novum, Karolinska Institute, Huddinge, Sweden.
    Cao, Yihai
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Karolinska Institute, Stockholm, Sweden; University of Leicester, Glenfield Hospital, Leicester, UK.
    Williams, Cecilia
    University of Houston, TX, USA .
    Dahlman-Wright, Karin
    Department of Biosciences and Nutrition, Novum, Karolinska Institute, Huddinge, Sweden.
    Genome-wide profiling of AP-1-regulated transcription provides insights into the invasiveness of triple-negative breast cancer2014In: Cancer Research, ISSN 0008-5472, E-ISSN 1538-7445, Vol. 74, no 14, p. 3983-3994Article in journal (Refereed)
    Abstract [en]

    Triple-negative breast cancer (TNBC) is an aggressive clinical subtype accounting for up to 20% of all breast cancers, but its malignant determinants remain largely undefined. Here, we show that in TNBC the overexpression of Fra-1, a component of the transcription factor AP-1, offers prognostic potential. Fra-1 depletion or its heterodimeric partner c-Jun inhibits the proliferative and invasive phenotypes of TNBC cells in vitro. Similarly, RNAi-mediated attenuation of Fra-1 or c-Jun reduced cellular invasion in vivo in a zebrafish tumor xenograft model. Exploring the AP-1 cistrome and the AP-1-regulated transcriptome, we obtained insights into the transcriptional regulatory networks of AP-1 in TNBC cells. Among the direct targets identified for Fra-1/c-Jun involved in proliferation, adhesion, and cell-cell contact, we found that AP-1 repressed the expression of E-cadherin by transcriptional upregulation of ZEB2 to stimulate cell invasion. Overall, this work illuminates the pathways through which TNBC cells acquire invasive and proliferative properties.

  • 5678.
    Zhao, Fei
    et al.
    University of Bristol, UK.
    French, David
    University of Bristol, UK.
    Manchaiah, Vinaya K. C.
    Swansea University, UK .
    Liang, Maojin
    University of Bristol, UK.
    Price, Sharon M.
    Finders University of South Australia, and Cora Barclay Centre, Adelaide, Australia.
    Music exposure and hearing health education: A review of knowledge, attitude and behavior in adolescents and young adults2012In: Health Education Journal, ISSN 0017-8969, E-ISSN 1748-8176, Vol. 71, no 6, p. 709-724Article in journal (Refereed)
    Abstract [en]

    Introduction: Adolescents and young adults have been shown to be the age group most at risk of music-induced hearing loss (MIHL), which is already evident and increasing among this group. Objective: The purpose of this review is to provide further insight into the effectiveness of education programmes on attitude and behaviour towards loud music exposure in adolescents and young adults, and to suggest positive and influential ways of delivering hearing health education. Methods: Literature searches were conducted using various databases, including PubMed, Google Scholar and Cumulative Index to Nursing and Allied Health Literature (CINAHL). Authors went through the abstracts of these articles to identify those which were potentially relevant; subsequently the full articles were retrieved. Results: This review highlights the dangers of significant exposure to music on hearing mechanics in adolescents and young adults, and shows that this danger continues to increase with modern music culture. Because the consequences are not immediate, it is difficult for the young to perceive the seriousness of a problem that may not present itself for many years. Conventional education may go a little way in helping to raise awareness but a raised awareness of consequences does not, in itself, change behaviour. There is a significant gap in literature regarding effective methods of education that will inspire attitude change, and have a bearing on actions. Conclusion: This review has concluded that there is a lack of understanding of how to best influence and educate adolescents and young adults in a way that will motivate and encourage a change in listening habits. It is of vital importance that these groups are made aware of the immediate and future dangers, and how changes in listening behaviour do not necessarily lower their enjoyment.

  • 5679.
    Zhao, Fei
    et al.
    University of Bristol, UK.
    Manchaiah, Vinaya K. C.
    Swansea University, UK.
    French, David
    University of Bristol, UK.
    Price, Sharob M.
    Swansea University, UK.
    Music exposure and hearing disorders: An overview2010In: International Journal of Audiology, ISSN 1499-2027, E-ISSN 1708-8186, Vol. 49, no 1, p. 54-64Article in journal (Refereed)
    Abstract [en]

    It has been generally accepted that excessive exposure to loud music causes various hearing symptoms (e.g. tinnitus) and consequently leads to a risk of permanent hearing damage, known as noise-induced hearing loss (NIHL). Such potential risk of NIHL due to loud music exposure has been widely investigated in musicians and people working in music venues. With advancements in sound technology and rapid developments in the music industry, increasing numbers of people, particularly adolescents and young adults, are exposing themselves to music on a voluntary basis at potentially harmful levels, and over a substantial period of time, which can also cause NIHL. However, because of insufficient audiometric evidence of hearing loss caused purely by music exposure, there is still disagreement and speculation about the risk of hearing loss from music exposure alone. Many studies have suggested using advanced audiological measurements as more sensitive and efficient tools to monitor hearing status as early indicators of cochlear dysfunction. The purpose of this review is to provide further insight into the potential risk of hearing loss caused by exposure to loud music, and thus contribute to further raising awareness of music induced hearing loss.

  • 5680.
    Zhao, Juan
    et al.
    Peking University, Peoples R China.
    Han, Zhenhui
    Kaifeng Childrens Hospital, Peoples R China.
    Zhang, Xi
    Kaifeng Childrens Hospital, Peoples R China.
    Du, Shuxu
    Capital Medical University, Peoples R China.
    Dong Liu, Angie
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Holmberg, Lukas
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Li, Xueying
    Peking University, Peoples R China.
    Lin, Jing
    Peking University, Peoples R China.
    Xiong, Zhenyu
    Kaifeng Childrens Hospital, Peoples R China.
    Gai, Yong
    Kaifeng Childrens Hospital, Peoples R China.
    Yang, Jinyan
    Peking University, Peoples R China.
    Liu, Ping
    Peking University, Peoples R China.
    Tang, Chaoshu
    Peking University, Peoples R China.
    Du, Junbao
    Peking University, Peoples R China; Minist Educ, Peoples R China.
    Jin, Hongfang
    Peking University, Peoples R China.
    A cross-sectional study on upright heart rate and BP changing characteristics: basic data for establishing diagnosis of postural orthostatic tachycardia syndrome and orthostatic hypertension2015In: BMJ Open, ISSN 2044-6055, E-ISSN 2044-6055, Vol. 5, no 6, article id e007356Article in journal (Refereed)
    Abstract [en]

    Objective: We aimed to determine upright heart rate and blood pressure (BP) changes to suggest diagnostic criteria for postural orthostatic tachycardia syndrome (POTS) and orthostatic hypertension (OHT) in Chinese children. Methods: In this cross-sectional study, 1449 children and adolescents aged 6-18 years were randomly recruited from two cities in China, Kaifeng in Henan province and Anguo in Hebei province. They were divided into two groups: 844 children aged 6-12 years (group I) and 605 adolescents aged 13-18 years (group II). Heart rate and BP were recorded during an active standing test. Results: 95th percentile (P-95) of delta heart rate from supine to upright was 38 bpm, with a maximum upright heart rate of 130 and 124 bpm in group I and group II, respectively. P-95 of delta systolic blood pressure (SBP) increase was 18 mm Hg and P-95 of upright SBP was 132 mm Hg in group I and 138 mm Hg in group II. P-95 of delta diastolic blood pressure (DBP) increase was 24 mm Hg in group I and 21 mm Hg in group II, and P-95 of upright DBP was 89 mm Hg in group I and 91 mm Hg in group II. Conclusions: POTS is suggested when delta heart rate is greater than= 38 bpm (for easy memory, greater than= 40 bpm) from supine to upright, or maximum heart rate greater than= 130 bpm (children aged 6-12 years) and greater than= 125 bpm (adolescents aged 13-18 years), associated with orthostatic symptoms. OHT is suggested when delta SBP (increase) is greater than= 20 mm Hg, and/or delta DBP (increase) greater than= 25 mm Hg (in children aged 6-12 years) or greater than= 20 mm Hg (in adolescents aged 13-18 years) from supine to upright; or upright BP greater than= 130/90 mm Hg (in children aged 6-12 years) or greater than= 140/90 mm Hg (in adolescents aged 13-18 years).

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  • 5681.
    Zhao, Lue Ping
    et al.
    Fred Hutchinson Canc Res Ctr, WA 98104 USA.
    Papadopoulos, George K.
    Technol Educ Inst Epirus, Greece; Univ Ioannina, Greece.
    Kwok, William W.
    Benaroya Res Inst Virginia Mason, WA USA.
    Xu, Bryan
    Univ Calif Berkeley, CA 94720 USA.
    Kong, Matthew
    Carnegie Mellon Univ, PA 15213 USA.
    Moustakas, Antonis K.
    Ionian Univ, Greece.
    Bondinas, George P.
    Technol Educ Inst Epirus, Greece; Univ Ioannina, Greece.
    Carlsson, Annelie
    Lund Univ, Sweden.
    Elding-Larsson, Helena
    Lund Univ, Sweden.
    Ludvigsson, Johnny
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Marcus, Claude
    Karolinska Inst, Sweden; Karolinska Inst, Sweden.
    Persson, Martina
    Karolinska Inst, Sweden; Karolinska Inst, Sweden.
    Samuelsson, Ulf
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Wang, Ruihan
    Fred Hutchinson Canc Res Ctr, WA 98104 USA.
    Pyo, Chul-Woo
    Fred Hutchinson Canc Res Ctr, WA 98104 USA.
    Nelson, Wyatt C.
    Fred Hutchinson Canc Res Ctr, WA 98104 USA.
    Geraghty, Daniel E.
    Fred Hutchinson Canc Res Ctr, WA 98104 USA.
    Lernmark, Ake
    Lund Univ, Sweden.
    Eleven Amino Acids of HLA-DRB1 and Fifteen Amino Acids of HLA-DRB3, 4, and 5 Include Potentially Causal Residues Responsible for the Risk of Childhood Type 1 Diabetes2019In: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 68, no 8, p. 1692-1704Article in journal (Refereed)
    Abstract [en]

    Next-generation targeted sequencing of HLA-DRB1 and HLA-DRB3, -DRB4, and -DRB5 (abbreviated as DRB345) provides high resolution of functional variant positions to investigate their associations with type 1 diabetes risk and with autoantibodies against insulin (IAA), GAD65 (GADA), IA-2 (IA-2A), and ZnT8 (ZnT8A). To overcome exceptional DR sequence complexity as a result of high polymorphisms and extended linkage disequilibrium among the DR loci, we applied a novel recursive organizer (ROR) to discover disease-associated amino acid residues. ROR distills disease-associated DR sequences and identifies 11 residues of DRB1, sequences of which retain all significant associations observed by DR genes. Furthermore, all 11 residues locate under/adjoining the peptide-binding groove of DRB1, suggesting a plausible functional mechanism through peptide binding. The 15 residues of DRB345, located respectively in the beta 49-55 homodimerization patch and on the face of the molecule shown to interact with and bind to the accessory molecule CD4, retain their significant disease associations. Further ROR analysis of DR associations with autoantibodies finds that DRB1 residues significantly associated with ZnT8A and DRB345 residues with GADA. The strongest association is between four residues (beta 14, beta 25, beta 71, and beta 73) and IA-2A, in which the sequence ERKA confers a risk association (odds ratio 2.15, P = 10(-18)), and another sequence, ERKG, confers a protective association (odds ratio 0.59, P = 10(-11)), despite a difference of only one amino acid. Because motifs of identified residues capture potentially causal DR associations with type 1 diabetes, this list of residuals is expected to include corresponding causal residues in this study population.

  • 5682.
    Zhao, Mingduo
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Speech language pathology, Audiology and Otorhinolaryngology. Linköping University, Faculty of Medicine and Health Sciences.
    Fridberger, Anders
    Linköping University, Department of Clinical and Experimental Medicine, Divison of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences.
    Stenfelt, Stefan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Speech language pathology, Audiology and Otorhinolaryngology. Linköping University, Faculty of Medicine and Health Sciences.
    Bone conduction hearing in the Guinea pig and the effect of artificially induced middle ear lesions2019In: Hearing Research, ISSN 0378-5955, E-ISSN 1878-5891, Vol. 379, p. 21-30Article in journal (Refereed)
    Abstract [en]

    Although human bone conduction (BC) hearing is well investigated, there is a lack of information about BC hearing in most other species. In humans, the amount of conductive loss is estimated as the difference between the air conduction (AC) and BC thresholds. Similar estimations for animals are difficult since in most species, the normal BC hearing thresholds have not been established. In the current study, the normal BC thresholds in the frequency range between 2 kHz and 20 kHz are investigated for the Guinea pig. Also, the effect of a middle ear lesion, here modelled by severing the ossicles (ossicular discontinuity) and gluing the ossicles to the bone (otosclerosis), is investigated for both AC and BC. The hearing thresholds in the Guinea pigs were estimated by a regression of the amplitude of the compound action potential (CAP) with stimulation level and was found robust and gave a high resolution of the threshold level. The reference for the BC thresholds was the cochlear promontory bone velocity. This reference enables comparison of BC hearing in animals, both intra and inter species, which is independent on the vibrator and stimulation position. The vibration was measured in three orthogonal directions where the dominating vibration directions was in line with the stimulation direction, here the ventral direction. The BC thresholds lay between -10 and 3 dB re 1 mu m/s. The slopes of CAP growth function were similar for AC and BC at low and high frequencies, but slightly lower for BC than AC at frequencies between 8 and 16 kHz. This was attributed to differences in the stimulus levels used for the slope estimation and not a real difference in CAP slopes between the stimulation modalities. Two kinds of middle ear lesions, ossicular discontinuity and stapes glued to the surrounding bone, gave threshold shifts of between 23 and 53 dB for AC while it was below 16 dB when the stimulation was by BC. Statistically different threshold shifts between the two types of lesions were found where the AC threshold shifts for a glued stapes at 2 and 4 kHz were 9-18 dB greater than for a severed ossicular chain, and the BC threshold shifts for a glued stapes at 4 and 12 kHz were 8-9 dB greater than fora severed ossicular chain. (C) 2019 Elsevier B.V. All rights reserved.

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  • 5683.
    Zhao, Senlin
    et al.
    Shanghai Jiao Tong University, Peoples R China.
    Sun, Hongcheng
    Shanghai Jiao Tong University, Peoples R China.
    Jiang, Weiliang
    Shanghai Jiao Tong University, Peoples R China.
    Mi, Yushuai
    Shanghai Jiao Tong University, Peoples R China.
    Zhang, Dongyuan
    Shanghai Jiao Tong University, Peoples R China.
    Wen, Yugang
    Shanghai Jiao Tong University, Peoples R China.
    Cheng, Dantong
    Shanghai Jiao Tong University, Peoples R China.
    Tang, Huamei
    Shanghai Jiao Tong University, Peoples R China.
    Wu, Shaohan
    Jiaxing Coll, Peoples R China.
    Yu, Yang
    Shanghai Jiao Tong University, Peoples R China.
    Liu, Xisheng
    Shanghai Jiao Tong University, Peoples R China.
    Cui, Weiyingqi
    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.
    Zhang, Meng
    Fudan University, Peoples R China.
    Sun, Xiao-Feng
    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 Oncology.
    Zhou, Zongguang
    Sichuan University, Peoples R China.
    Peng, Zhihai
    Shanghai Jiao Tong University, Peoples R China.
    Yan, Dongwang
    Shanghai Jiao Tong University, Peoples R China.
    miR-4775 promotes colorectal cancer invasion and metastasis via the Smad7/TGF beta-mediated epithelial to mesenchymal transition2017In: Molecular Cancer, ISSN 1476-4598, E-ISSN 1476-4598, Vol. 16, article id 12Article in journal (Refereed)
    Abstract [en]

    Background: Despite advancements in the diagnosis and treatment of colorectal cancer (CRC), many patients die because of tumor metastasis or recurrence. Therefore, identifying new prognostic markers and elucidating the mechanisms of CRC metastasis and recurrence will help to improve the prognosis of the disease. As dysregulation of microRNAs is strongly related to cancer progression, the aim of this study was to identify the role of miR-4775 in the prognosis of CRC patients and the underling mechanisms involved in CRC progression. Methods: qPCR and in situ hybridization were used to evaluate the expression of miR-4775 in 544 pairs of paraffin-embedded normal and CRC tissues. Kaplan-Meier analysis with the log-rank test was used for survival analyses. Immunohistochemical staining was applied to investigate the expression of miR-4775-regulated Smad7/TGF beta pathway-associated markers. In vitro and in vivo invasion and metastasis assays were used to explore the function of miR-4775 in the progression of CRC. Results: miR-4775 was identified as a high-risk factor for CRC metastasis and recurrence, with high levels predicting poor survival among the 544 studied CRC patients. Furthermore, high miR-4775 expression promoted the invasion of CRC cells as well as metastasis and the epithelial to mesenchymal transition (EMT) via Smad7-mediated activation of TGF beta signaling both in vitro and in vivo. Downregulating miR-4775 or overexpressing Smad7 reversed the tumor-promoting roles of miR-4775/ Smad7/TGF beta in vitro and in vivo. Conclusion: miR-4775 promotes CRC metastasis and recurrence in a Smad7/TGF beta signaling-dependent manner, providing a new therapeutic target for inhibiting the metastasis or recurrence of the disease.

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  • 5684.
    Zhong, Liang
    et al.
    Natl Heart Ctr Singapore, Singapore; Natl Univ Singapore, Singapore.
    Schrauben, Eric M.
    Hosp Sick Children, Canada.
    Garcia, Julio
    Univ Calgary, Canada.
    Uribe, Sergio
    Pontificia Univ Catolica Chile, Chile.
    Grieve, Stuart M.
    Univ Sydney, Australia; Royal Prince Alfred Hosp, Australia.
    Elbaz, Mohammed S. M.
    Northwestern Univ, IL 60611 USA.
    Barker, Alex J.
    Univ Colorado, CO 80202 USA.
    Geiger, Julia
    Univ Childrens Hosp Zurich, Switzerland.
    Nordmeyer, Sarah
    German Heart Ctr, Germany; Charite, Germany.
    Marsden, Alison
    Stanford Univ, CA 94305 USA.
    Carlsson, Marcus
    Lund Univ, Sweden.
    Tan, Ru-San
    Natl Heart Ctr Singapore, Singapore; Natl Univ Singapore, Singapore.
    Garg, Pankaj
    Univ Sheffield, England.
    Westenberg, Jos J. M.
    Leiden Univ, Netherlands.
    Markl, Michael
    Northwestern Univ, IL 60611 USA.
    Ebbers, Tino
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Intracardiac 4D Flow MRI in Congenital Heart Disease: Recommendations on Behalf of the ISMRM Flow & Motion Study Group2019In: Journal of Magnetic Resonance Imaging, ISSN 1053-1807, E-ISSN 1522-2586, Vol. 50, no 3, p. 677-681Article in journal (Refereed)
    Abstract [en]

    Technical Efficacy: Stage 5 J. Magn. Reson. Imaging 2019.

  • 5685.
    Zhou, Jie
    et al.
    Johann Wolfgang Goethe-University Frankfurt, Germany.
    Damdimopoulos, Anastassios E.
    Novum, Karolinska Institute, Huddinge, Sweden.
    Spyrou, Giannis
    Novum, Karolinska Institute, Huddinge, Sweden and Foundation of Biomedical Research, Academy of Athens, Greece.
    Brüne, Bernhard
    Johann Wolfgang Goethe-University Frankfurt, Germany.
    Thioredoxin 1 and Thioredoxin 2 Have Opposed Regulatory Functions on Hypoxia-inducible Factor-1α*2007In: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 282, no 10, p. 7482-7490Article in journal (Refereed)
    Abstract [en]

    Hypoxia inducible factor 1 (HIF-1), a key regulator for adaptation to hypoxia, is composed of HIF-1alpha and HIF-1beta. In this study, we present evidence that overexpression of mitochondria-located thioredoxin 2 (Trx2) attenuated hypoxia-evoked HIF-1alpha accumulation, whereas cytosolic thioredoxin 1 (Trx1) enhanced HIF-1alpha protein amount. Transactivation of HIF-1 is decreased by overexpression of Trx2 but stimulated by Trx1. Inhibition of proteasomal degradation of HIF-1alpha in Trx2-overexpressing cells did not fully restore HIF-1alpha protein levels, while HIF-1alpha accumulation was enhanced in Trx1-overexpressing cells. Reporter assays showed that cap-dependent translation is increased by Trx1 and decreased by Trx2, whereas HIF-1alpha mRNA levels remained unaltered. These data suggest that thioredoxins affect the synthesis of HIF-1alpha. Trx1 facilitated synthesis of HIF-1alpha by activating Akt, p70S6K, and eIF-4E, known to control cap-dependent translation. In contrast, Trx2 attenuated activities of Akt, p70S6K, and eIF-4E and provoked an increase in mitochondrial reactive oxygen species production. MitoQ, a mitochondria specific antioxidant, reversed HIF-1alpha accumulation as well as Akt activation under hypoxia in Trx2 cells, supporting the notion of translation control mechanisms in affecting HIF-1alpha protein accumulation.

  • 5686.
    Zhou, Jie
    et al.
    Institute of Biochemistry I, Faculty of Medicine, Johann Wolfgang Goethe-University Frankfurt, Germany.
    Eleni, Chantzoura
    Biochemical Research Foundation, Academy of Athens, Greece.
    Spyrou, Giannis
    Biochemical Research Foundation, Academy of Athens, Greece.
    Brüne, Bernhard
    Institute of Biochemistry I, Faculty of Medicine, Johann Wolfgang Goethe-University Frankfurt, Germany.
    The mitochondrial thioredoxin system regulates nitric oxide-induced HIF-1a protein2008In: Free Radical Biology & Medicine, ISSN 0891-5849, E-ISSN 1873-4596, Vol. 44, no 1, p. 91-98Article in journal (Refereed)
    Abstract [en]

    Hypoxia-inducible factor-1 (HIF-1), consisting of two subunits, HIF-1alpha and HIF-1beta, is a key regulator for adaptation to low oxygen availability, i.e., hypoxia. Compared to the constitutively expressed HIF-1beta, HIF-1alpha is regulated by hypoxia but also under normoxia (21% O(2)) by several stimuli, including nitric oxide (NO). In this study, we present evidence that overexpression of mitochondrial-located thioredoxin 2 (Trx2) or thioredoxin reductase 2 (TrxR2) attenuated NO-evoked HIF-1alpha accumulation and transactivation of HIF-1 in HEK293 cells. In contrast, cytosolic-located thioredoxin 1 (Trx1) enhanced HIF-1alpha protein amount and activity under NO treatments. Taking into consideration that thioredoxins affect the synthesis of HIF-1alpha by altering Akt/mTOR signaling, we herein show that p42/44 mitogen-activated protein kinase and p70S6 kinase are involved. Moreover, intracellular ATP was increased in Trx1-overexpressing cells but reduced in cells overexpressing Trx2 or TrxR2, providing thus an understanding of how protein synthesis is regulated by thioredoxins.

  • 5687.
    Zhou, Jin
    et al.
    Sichuan University, Peoples R China Sichuan University, Peoples R China .
    Yang, Lie
    Sichuan University, Peoples R China Sichuan University, Peoples R China .
    Li, Yuan
    Sichuan University, Peoples R China Sichuan University, Peoples R China .
    Arbman, Gunnar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Norrköping.
    Chen, Ke-Ling
    Sichuan University, Peoples R China Sichuan University, Peoples R China .
    Zhou, Bin
    Sichuan University, Peoples R China Sichuan University, Peoples R China .
    Yu, Yong-Yang
    Sichuan University, Peoples R China Sichuan University, Peoples R China .
    Wang, Cun
    Sichuan University, Peoples R China Sichuan University, Peoples R China .
    Mo, Xian-Ming
    Sichuan University, Peoples R China Sichuan University, Peoples R China .
    Lu, You
    Sichuan University, Peoples R China .
    Zhou, Zong-Guang
    Sichuan University, Peoples R China Sichuan University, Peoples R China .
    Sun, Xiao-Feng
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    The prognostic significance of peroxisome proliferator-activated receptor beta expression in the vascular endothelial cells of colorectal cancer2014In: Journal of gastroenterology, ISSN 0944-1174, E-ISSN 1435-5922, Vol. 49, no 3, p. 436-445Article in journal (Refereed)
    Abstract [en]

    Currently, little is known regarding the role of peroxisome proliferator-activated receptor-beta (PPAR beta) in the vascular endothelial cells (VECs) of colorectal cancers (CRCs). The aim of this study was to investigate the relationship of PPAR beta expression in the VECs of CRCs in terms of the prognosis and clinicopathological features of CRC patients. The expression and localization of PPAR beta in the primary cancers and the matched normal mucosal samples of 141 Swedish CRC patients were analyzed in terms of its correlation with clinicopathological features and the expression of angiogenesis-related genes. This study also included 92 Chinese CRC patients. PPAR beta was predominantly localized in the cytoplasm and was significantly downregulated in the VECs of CRC compared to that of the normal mucosa. The low expression levels of PPAR beta in the VECs of CRC were statistically correlated with enhanced differentiation, early staging and favorable overall survival and were associated with the increased expression of VEGF and D2-40. The patients exhibiting elevated expression of PPAR beta in CRC cells but reduced expression in VECs exhibited more favorable survival compared with the other patients, whereas the patients with reduced expression of PPAR beta in CRC cells but increased expression in VECs exhibited less favorable prognosis. PPAR beta might play a tumor suppressor role in CRC cells in contrast to a tumor promoter role in the VECs of CRCs.

  • 5688.
    Zhou, Xin
    et al.
    Sichuan Univ, Peoples R China.
    Shang, Yan-Na
    Sichuan Univ, Peoples R China.
    Lu, Ran
    Sichuan Univ, Peoples R China.
    Fan, Chuanwen
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Sichuan Univ, Peoples R China; Sichuan Univ, Peoples R China.
    Mo, Xian-Ming
    Sichuan Univ, Peoples R China.
    High ANKZF1 expression is associated with poor overall survival and recurrence-free survival in colon cancer2019In: Future Oncology, ISSN 1479-6694, E-ISSN 1744-8301, Vol. 15, no 18, p. 2093-2106Article in journal (Refereed)
    Abstract [en]

    Aim: To investigate the association and prognostic value of ANKZF1 gene for survival in colorectal cancer, the mechanism of ANKZF1 level alteration and correlated signaling pathways ANKZF1 is involved. Patients amp; methods: The Cancer Genome Atlas COREAD dataset was analyzed by bioinformatical investigation. Results: High ANKZF1 expression is associated with poor overall survival (hazard ratio [HR]: 2.094; 95% CI: 1.188-3.689; p=0.011) and recurrence-free survival (HR: 1.762; 95% CI: 1.021-3.042; p=0.042) in colon cancer. Bioinformatical analysis showed ANKZF1 was upregulated by amplification and exon expression. ANKZF1 was associated with angiogenesis and cancer signaling pathways. Conclusion: High ANKZF1 is an independent factor of poor survival (overall survival and recurrence-free survival) in colon cancer by taking part in angiogenesis and some cancer signaling pathways.

  • 5689.
    Zhou, Yin
    et al.
    Sichuan University, Peoples R China.
    Li, Yibo
    Sichuan University, Peoples R China.
    Zhou, Bin
    Sichuan University, Peoples R China.
    Chen, Keling
    Sichuan University, Peoples R China.
    Lyv, Zhaoying
    Sichuan University, Peoples R China.
    Huang, Dongmei
    Sichuan University, Peoples R China.
    Liu, Bin
    Sichuan University, Peoples R China.
    Xu, Zhicheng
    Sichuan University, Peoples R China.
    Xiang, Bo
    Sichuan University, Peoples R China.
    Jin, Shuguang
    Sichuan University, Peoples R China.
    Sun, Xiao-Feng
    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 Oncology.
    Li, Yuan
    Sichuan University, Peoples R China.
    Inflammation and Apoptosis: Dual Mediator Role for Toll-like Receptor 4 in the Development of Necrotizing Enterocolitis2017In: Inflammatory Bowel Diseases, ISSN 1078-0998, E-ISSN 1536-4844, Vol. 23, no 1, p. 44-56Article in journal (Refereed)
    Abstract [en]

    Background: Necrotizing enterocolitis (NEC) is the leading cause of neonatal gastrointestinal mortality; effective interventions are lacking with limited understanding of the pathogenesis of NEC. The importance of Toll-like receptor 4 (TLR4) signaling in NEC is well documented; however, the potential mechanisms that regulate enterocyte inflammation and apoptosis remain unclear. The aim of this study was to characterize the role of TLR4-mediated inflammation and apoptosis in the development of NEC and to determine the major apoptotic pathways and regulators in the process. Methods: TLR4-deficient C57BL/10ScNJ mice and lentivirus-mediated stable TLR4-silent cell line (IEC-6) were used. NEC was induced by formula gavage, cold, hypoxia, combined with lipopolysaccharide in vivo or lipopolysaccharide stimulation in vitro. Enterocyte apoptosis was evaluated by TUNEL or Annexin analysis. The expression of TLR4, caspase3, caspase8, caspase9, Bip, Bax, Bcl-2, and RIP was detected by Western blot and immunofluorescence. Inflammatory factors such as tumor necrosis factor-a and interleukin-2 were examined by Luminex. Results: Defect of TLR4 led to suppressed enterocytes apoptosis both in vitro and in vivo; the expression of caspase3, caspase8, Bip, and Bax was decreased; and caspase9 and Bcl-2 were increased. NEC severity was attenuated in TLR4-deficient mice compared with wild-type counterparts, and enterocytes apoptosis was correlated with NEC severity. RIP and cytokine level of tumor necrosis factor-a and interleukin-2 were also decreased. Conclusions: TLR4-induced inflammation and apoptosis play a critical role in the pathogenesis of NEC. TLR4 inhibition, combined with extrinsic (caspase8) and/or endoplasmic reticulum stress (Bip) apoptosis signaling blockade could serve as a potential effective treating strategy for NEC.

  • 5690.
    Zhou, Yuan
    et al.
    Nanjing University, Peoples R China; Nanjing University, Peoples R China; Nanjing University, Peoples R China.
    Wang, Hui
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Wang, Cong
    Nanjing University, Peoples R China; Nanjing University, Peoples R China; Nanjing University, Peoples R China.
    Qiu, Xuefeng
    Nanjing University, Peoples R China.
    Benson, Mikael
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Allergy Center.
    Yin, Xiaoqin
    Nanjing University, Peoples R China; Nanjing University, Peoples R China; Nanjing University, Peoples R China.
    Xiang, Zou
    University of Gothenburg, Sweden.
    Li, Dongmei
    Nanjing University, Peoples R China; Nanjing University, Peoples R China; Nanjing University, Peoples R China.
    Han, Xiaodong
    Nanjing University, Peoples R China; Nanjing University, Peoples R China; Nanjing University, Peoples R China.
    Roles of miRNAs in microcystin-LR-induced Sertoli cell toxicity2015In: Toxicology and Applied Pharmacology, ISSN 0041-008X, E-ISSN 1096-0333, Vol. 287, no 1Article in journal (Refereed)
    Abstract [en]

    Microcystin (MC)-LR, a cyclic heptapeptide, is a potent reproductive system toxin. To understand the molecular mechanisms of MC-induced reproductive system cytotoxicity, we evaluated global changes of miRNA and mRNA expression in mouse Sertoli cells following MC-LR treatment. Our results revealed that the exposure to MC-LR resulted in an altered miRNA expression profile that might be responsible for the modulation of mRNA expression. Bio-functional analysis indicated that the altered genes were involved in specific cellular processes, including cell death and proliferation. Target gene analysis suggested that junction injury in Sertoli cells exposed to MC-LR might be mediated by miRNAs through the regulation of the Sertoli cell-Sertoli cell pathway. Collectively, these findings may enhance our understanding on the modes of action of MC-LR on mouse Sertoli cells as well as the molecular mechanisms underlying the toxicity of MC-LR on the male reproductive system.

  • 5691.
    Zhou, Zien
    et al.
    Univ New South Wales, Australia; Shanghai Jiao Tong Univ, Peoples R China.
    Lindley, Richard I.
    George Inst Global Hlth, Australia; Univ Sydney, Australia.
    Rådholm, Karin
    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. George Inst Global Hlth, Australia; Univ Sydney, Australia.
    Jenkins, Bronwyn
    Royal North Shore Hosp, Australia.
    Watson, John
    Univ New South Wales, Australia.
    Perkovic, Vlado
    Univ New South Wales, Australia; Univ Sydney, Australia; Royal North Shore Hosp, Australia.
    Mahaffey, Kenneth W.
    Stanford Univ, CA 94305 USA.
    de Zeeuw, Dick
    Univ Groningen, Netherlands.
    Fulcher, Greg
    Univ Sydney, Australia; Royal North Shore Hosp, Australia.
    Shaw, Wayne
    Janssen Res and Dev LLC, NJ USA.
    Oh, Richard
    Janssen Res and Dev LLC, NJ USA.
    Desai, Mehul
    Janssen Res and Dev LLC, NJ USA.
    Matthews, David R.
    Univ Oxford, England; Univ Oxford, England.
    Neal, Bruce
    Univ New South Wales, Australia; Univ New South Wales, Australia; Univ Sydney, Australia; Imperial Coll London, England.
    Canagliflozin and Stroke in Type 2 Diabetes Mellitus Results From the Randomized CANVAS Program Trials2019In: Stroke, ISSN 0039-2499, E-ISSN 1524-4628, Vol. 50, no 2, p. 396-404Article in journal (Refereed)
    Abstract [en]

    Background and Purpose-This study reports the detailed effects of canagliflozin on stroke, stroke subtypes, and vascular outcomes in participants with and without cerebrovascular disease (stroke or transient ischemic attack) at baseline from the CANVAS (Canagliflozin Cardiovascular Assessment Study) Program. Methods-The CANVAS Program, comprising 2 similarly designed and conducted clinical trials, randomly assigned 10 142 participants with type 2 diabetes mellitus and high cardiovascular risk to canagliflozin or placebo. Its primary outcome was a composite of major adverse cardiovascular events. The main outcome of interest for this report was fatal or nonfatal stroke. Additional exploratory outcomes were stroke subtypes and other vascular outcomes defined according to standard criteria. Results-There were 1 958 (19%) participants with prior stroke or transient ischemic attack at baseline. These individuals were older, more frequently women, and had higher rates of heart failure, atrial fibrillation, and microvascular disease (all Pamp;lt;0.001) compared with those without such a history. There were 309 participants with stroke events during followup (123 had prior stroke or transient ischemic attack at baseline and 186 did not), at a rate of 7.93/1000 patient-years among those assigned canagliflozin and 9.62/1000 patient-years among placebo (hazard ratio, 0.87; 95% CI, 0.691.09). Analysis of stroke subtypes found no effect on ischemic stroke (n=253, hazard ratio, 0.95; 95% CI, 0.74-1.22), a significant reduction for hemorrhagic stroke (n=30, hazard ratio, 0.43; 95% CI, 0.20-0.89) and no effect on undetermined stroke (n=29, hazard ratio, 1.04; 95% CI, 0.48-2.22). Effects on other cardiovascular outcomes were comparable among participants with and without stroke or transient ischemic attack at baseline. Conclusions-There were too few events in the CANVAS Program to separately define the effects of canagliflozin on stroke, but benefit is more likely than harm. The observed possible protective effect for hemorrhagic stroke was based on small numbers but warrants further investigation.

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  • 5692.
    Zhu, Mingzhu
    et al.
    Peking University of First Hospital, Peoples R China .
    Du, Junbao
    Peking University of First Hospital, Peoples R China Minist Educ, Peoples R China .
    Dong Liu, Angie
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Health Sciences.
    Holmberg, Lukas
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Health Sciences.
    Tang, Chaoshu
    Minist Educ, Peoples R China Peking University, Peoples R China .
    Jin, Hongfang
    Peking University of First Hospital, Peoples R China .
    Effect of endogenous sulfur dioxide in regulating cardiovascular oxidative stress2014In: Histology and Histopathology, ISSN 0213-3911, E-ISSN 1699-5848, Vol. 29, no 9, p. 1107-1111Article, review/survey (Refereed)
    Abstract [en]

    In the middle of the 1980s, nitric oxide received extensive attention because of its significant effects in life science. Then, carbon monoxide and hydrogen sulfide were discovered to be gasotransmitters playing important roles in regulating cellular homeostasis. As a common air pollutant, sulfur dioxide (SO2) can cause great harm to the human body by producing free radicals, which causes oxidative damage to various organs. Recently, endogenous SO2 was found to be produced in the cardiovascular system and might be a bioactive molecule regulating the physiological activities including cardiovascular oxidative stress.

  • 5693. Order onlineBuy this publication >>
    Ziegelasch, Michael
    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, Department of Rheumatology.
    Diagnostic and prognostic potential of joint imaging in patients with anti-citrullinated protein antibodies2018Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The introduction of novel therapeutic strategies set new goals for the patients’ outcome, which aims to achieve remission. This goal requires early diagnosis of RA and prompt efficient pharmacotherapy. The introduction of anti-citrullinated protein antibodies (ACPA) two decades ago allowed an earlier RA diagnosis. However, there are indications that ACPA positivity is still associated with higher rates of radiographic damage. As the small joints in hands and feet commonly are the first involved sites of inflammation, the role of different imaging modalities were studied regarding their diagnostic and prognostic impact for assessment of arthritis in RA. Further, ultrasound (US) and radiography were used to study the association between RA-specific antibodies and the occurrence of arthritis and joint damage in systemic lupus erythematosus (SLE).

    The use of US allows assessment of soft tissue like joint capsules, tendons and bursae. Used for a live scanning, it is easy to detect effusions and edema. Doppler indicates vasoproliferation were inflammation is present. Also, US seems to be more sensitive than radiography to detect minimal structural changes located at bone surfaces. We wanted to investigate whether US findings in a pre-RA stage can predict development of arthritis.

    Digital X-ray radiogrammetry (DXR) is a technique based on computerized analyses of standard hand radiographs to calculate peripheral bone mineral density (BMD) of the three middle metacarpal bones (DXR-BMD). In order for early treatment decisions, we aimed to study whether changes in DXR-BMD loss after 3 months can predict radiographic damage in early RA.

    In conclusion, the studies showed that ACPA-positivity is still associated with a higher risk of radiographic damage regardless of early treatment decisions. Therefore, close radiographic monitoring and readiness to intensive treatment is warranted in ACPA-positive patients. This thesis also shows that erosions detected by US in ACPA-positive patients with arthralgia predict development of clinical arthritis. Also, the magnitude of DXR-BMD loss helps identify patients at higher risk for future radiographic damage, and may therefore help to improve early treatment decisions. Finally, US and radiography confirm a higher rate of arthritis and erosions also in SLE patients who are positive for RA-specific antibodies.

    List of papers
    1. Antibodies against carbamylated proteins and cyclic citrullinated peptides in systemic lupus erythematosus: results from two well-defined European cohorts.
    Open this publication in new window or tab >>Antibodies against carbamylated proteins and cyclic citrullinated peptides in systemic lupus erythematosus: results from two well-defined European cohorts.
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    2016 (English)In: Arthritis Research & Therapy, ISSN 1478-6354, E-ISSN 1478-6362, Vol. 18, no 1Article in journal (Refereed) Published
    Abstract [en]

    BACKGROUND: Articular manifestations are common in systemic lupus erythematosus (SLE) whereas erosive disease is not. Antibodies to cyclic citrullinated peptide (anti-CCP) are citrulline-dependent in rheumatoid arthritis (RA), whereas the opposite is suggested in SLE, as reactivity with cyclic arginine peptide (CAP) is typically present. Antibodies targeting carbamylated proteins (anti-CarP) may occur in anti-CCP/rheumatoid factor (RF)-negative cases long before clinical onset of RA. We analysed these antibody specificities in sera from European patients with SLE in relation to phenotypes, smoking habits and imaging data.

    METHODS: Cases of SLE (n = 441) from Linköping, Sweden, and Leiden, the Netherlands, were classified according to American College of Rheumatology (ACR) and/or Systemic Lupus Erythematosus International Collaborating Clinics (SLICC) criteria. IgG anti-CCP, anti-CAP and anti-CarP were analysed by immunoassays. Radiographic data from 102 Swedish patients were available.

    RESULTS: There were 16 Linköping (6.8%) and 11 Leiden patients (5.4%) who were anti-CCP-positive, of whom approximately one third were citrulline-dependent: 40/441 (9.1%) were anti-CarP-positive, and 33% of the anti-CarP-positive patients were identified as anti-CCP-positive. No associations were found comparing anti-CCP or anti-CarP with ACR-defined phenotypes, immunologic abnormalities or smoking habits. Radiographically confirmed erosions were found in 10 patients, and were significantly associated with anti-CCP, anti-CarP and RF. Musculoskeletal ultrasonography scores were higher in anti-CCP-positive compared to anti-CCP-negative patients.

    CONCLUSIONS: In the hitherto largest anti-CarP study in SLE, we demonstrate that anti-CarP is more prevalent than anti-CCP and that the overlap is limited. We obtained some evidence that both autoantibodies seem to be associated with erosivity. Similar pathogenetic mechanisms to those seen in RA may be relevant in a subgroup of SLE cases with a phenotype dominated by arthritis.

    Place, publisher, year, edition, pages
    BioMed Central, 2016
    National Category
    Rheumatology and Autoimmunity
    Identifiers
    urn:nbn:se:liu:diva-133852 (URN)10.1186/s13075-016-1192-x (DOI)000390276600002 ()27912793 (PubMedID)
    Note

    Funding agencies: County Council of Ostergotland; Swedish Society for Medical Research; Swedish Rheumatism Association; Swedish Society of Medicine; Professor Nanna Svartz foundation; King Gustaf V 80-year foundation; Dutch Arthritis Foundation; IMI JU project, BeTheCure [

    Available from: 2017-01-12 Created: 2017-01-12 Last updated: 2019-01-04
    2. Decrease in bone mineral density during three months after diagnosis of early rheumatoid arthritis measured by digital X-ray radiogrammetry predicts radiographic joint damage after one year
    Open this publication in new window or tab >>Decrease in bone mineral density during three months after diagnosis of early rheumatoid arthritis measured by digital X-ray radiogrammetry predicts radiographic joint damage after one year
    Show others...
    2017 (English)In: Arthritis Research & Therapy, ISSN 1478-6354, E-ISSN 1478-6362, Vol. 19, article id 195Article in journal (Refereed) Published
    Abstract [en]

    Background: Periarticular osteopenia is an early sign of incipient joint injury in rheumatoid arthritis (RA), but cannot be accurately quantified using conventional radiography. Digital X-ray radiogrammetry (DXR) is a computerized technique to estimate bone mineral density (BMD) from hand radiographs. The aim of this study was to evaluate whether decrease in BMD of the hands (BMD loss), as determined by DXR 3 months after diagnosis, predicts radiographic joint damage after 1 and 2 years in patients with early RA. Methods: Patients (n = 176) with early RA (amp;lt; 12 months after onset of symptoms) from three different Swedish rheumatology centers were consecutively included in the study, and 167 of these patients were included in the analysis. Medication was given in accordance with Swedish guidelines, and the patients were followed for 2 years. Rheumatoid factor and antibodies to cyclic citrullinated peptides (anti-CCP) were measured at baseline, and 28-joint Disease Activity Score (DAS28) was assessed at each visit. Radiographs of the hands and feet were obtained at baseline, 3 months (hands only) and 1 and 2 years. Baseline and 1-year and 2-year radiographs were evaluated by the Larsen score. Radiographic progression was defined as a difference in Larsen score above the smallest detectable change. DXR-BMD was measured at baseline and after 3 months. BMD loss was defined as moderate when the decrease in BMD was between 0.25 and 2.5 mg/cm(2)/month and as severe when the decrease was greater than 2.5 mg/cm(2)/month. Multivariate regression was applied to test the association between DXR-BMD loss and radiographic damage, including adjustments for possible confounders. Results: DXR-BMD loss during the initial 3 months occurred in 59% of the patients (44% moderate, 15% severe): 32 patients (19%) had radiographic progression at 1 year and 45 (35%) at 2 years. In multiple regression analyses, the magnitude of DXR-BMD loss was significantly associated with increase in Larsen score between baseline and 1 year (p = 0.033, adjusted R-squared = 0.069). Conclusion: DXR-BMD loss during the initial 3 months independently predicted radiographic joint damage at 1 year in patients with early RA. Thus, DXR-BMD may be a useful tool to detect ongoing joint damage and thereby to improve individualization of therapy in early RA.

    Place, publisher, year, edition, pages
    BIOMED CENTRAL LTD, 2017
    Keywords
    Digital X-ray radiogrammetry; Bone mineral density; Disease progression; Early rheumatoid arthritis
    National Category
    Rheumatology and Autoimmunity
    Identifiers
    urn:nbn:se:liu:diva-141121 (URN)10.1186/s13075-017-1403-0 (DOI)000409495000002 ()28865482 (PubMedID)
    Note

    Funding Agencies|Swedish Rheumatism Association; Norrbacka-Eugenia foundation; King Gustav V 80-year Foundation; Swedish Medical Society; ALF Grants from Region Ostergotland; Linkoping University Hospital Research Fund; Foundation for Assistance to Disabled People in Skane (Stiftelsen for Bistand at Rorelsehindrade i Skane)

    Available from: 2017-09-27 Created: 2017-09-27 Last updated: 2019-01-04
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    Diagnostic and prognostic potential of joint imaging in patients with anti-citrullinated protein antibodies
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  • 5694.
    Ziegelasch, Michael
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Forslind, Kristina
    Helsingborg Hospital, Sweden; Lund University, Sweden.
    Skogh, Thomas
    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, Department of Rheumatology.
    Riklund, Katrine
    Umeå University Hospital, Sweden.
    Kastbom, Alf
    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, Department of Rheumatology.
    Berglin, Ewa
    Umeå University Hospital, Sweden.
    Decrease in bone mineral density during three months after diagnosis of early rheumatoid arthritis measured by digital X-ray radiogrammetry predicts radiographic joint damage after one year2017In: Arthritis Research & Therapy, ISSN 1478-6354, E-ISSN 1478-6362, Vol. 19, article id 195Article in journal (Refereed)
    Abstract [en]

    Background: Periarticular osteopenia is an early sign of incipient joint injury in rheumatoid arthritis (RA), but cannot be accurately quantified using conventional radiography. Digital X-ray radiogrammetry (DXR) is a computerized technique to estimate bone mineral density (BMD) from hand radiographs. The aim of this study was to evaluate whether decrease in BMD of the hands (BMD loss), as determined by DXR 3 months after diagnosis, predicts radiographic joint damage after 1 and 2 years in patients with early RA. Methods: Patients (n = 176) with early RA (amp;lt; 12 months after onset of symptoms) from three different Swedish rheumatology centers were consecutively included in the study, and 167 of these patients were included in the analysis. Medication was given in accordance with Swedish guidelines, and the patients were followed for 2 years. Rheumatoid factor and antibodies to cyclic citrullinated peptides (anti-CCP) were measured at baseline, and 28-joint Disease Activity Score (DAS28) was assessed at each visit. Radiographs of the hands and feet were obtained at baseline, 3 months (hands only) and 1 and 2 years. Baseline and 1-year and 2-year radiographs were evaluated by the Larsen score. Radiographic progression was defined as a difference in Larsen score above the smallest detectable change. DXR-BMD was measured at baseline and after 3 months. BMD loss was defined as moderate when the decrease in BMD was between 0.25 and 2.5 mg/cm(2)/month and as severe when the decrease was greater than 2.5 mg/cm(2)/month. Multivariate regression was applied to test the association between DXR-BMD loss and radiographic damage, including adjustments for possible confounders. Results: DXR-BMD loss during the initial 3 months occurred in 59% of the patients (44% moderate, 15% severe): 32 patients (19%) had radiographic progression at 1 year and 45 (35%) at 2 years. In multiple regression analyses, the magnitude of DXR-BMD loss was significantly associated with increase in Larsen score between baseline and 1 year (p = 0.033, adjusted R-squared = 0.069). Conclusion: DXR-BMD loss during the initial 3 months independently predicted radiographic joint damage at 1 year in patients with early RA. Thus, DXR-BMD may be a useful tool to detect ongoing joint damage and thereby to improve individualization of therapy in early RA.

    Download full text (pdf)
    fulltext
  • 5695.
    Ziegelasch, Michael
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Region Östergötland, Heart and Medicine Center, Department of Rheumatology. Linköping University, Faculty of Medicine and Health Sciences.
    van Delft, Myrthe A M
    Leiden University Medical Center, Leiden, The Netherlands.
    Wallin, Philip
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science.
    Skogh, Thomas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Region Östergötland, Heart and Medicine Center, Department of Rheumatology. Linköping University, Faculty of Medicine and Health Sciences.
    Magro-Checa, César
    Leiden University Medical Center, Leiden, The Netherlands.
    Steup-Beekman, Gerda M
    Leiden University Medical Center, Leiden, The Netherlands.
    Trouw, Leendert A
    Leiden University Medical Center, Leiden, The Netherlands.
    Kastbom, Alf
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Region Östergötland, Heart and Medicine Center, Department of Rheumatology. Linköping University, Faculty of Medicine and Health Sciences.
    Sjöwall, Christopher
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Region Östergötland, Heart and Medicine Center, Department of Rheumatology. Linköping University, Faculty of Medicine and Health Sciences.
    Antibodies against carbamylated proteins and cyclic citrullinated peptides in systemic lupus erythematosus: results from two well-defined European cohorts.2016In: Arthritis Research & Therapy, ISSN 1478-6354, E-ISSN 1478-6362, Vol. 18, no 1Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Articular manifestations are common in systemic lupus erythematosus (SLE) whereas erosive disease is not. Antibodies to cyclic citrullinated peptide (anti-CCP) are citrulline-dependent in rheumatoid arthritis (RA), whereas the opposite is suggested in SLE, as reactivity with cyclic arginine peptide (CAP) is typically present. Antibodies targeting carbamylated proteins (anti-CarP) may occur in anti-CCP/rheumatoid factor (RF)-negative cases long before clinical onset of RA. We analysed these antibody specificities in sera from European patients with SLE in relation to phenotypes, smoking habits and imaging data.

    METHODS: Cases of SLE (n = 441) from Linköping, Sweden, and Leiden, the Netherlands, were classified according to American College of Rheumatology (ACR) and/or Systemic Lupus Erythematosus International Collaborating Clinics (SLICC) criteria. IgG anti-CCP, anti-CAP and anti-CarP were analysed by immunoassays. Radiographic data from 102 Swedish patients were available.

    RESULTS: There were 16 Linköping (6.8%) and 11 Leiden patients (5.4%) who were anti-CCP-positive, of whom approximately one third were citrulline-dependent: 40/441 (9.1%) were anti-CarP-positive, and 33% of the anti-CarP-positive patients were identified as anti-CCP-positive. No associations were found comparing anti-CCP or anti-CarP with ACR-defined phenotypes, immunologic abnormalities or smoking habits. Radiographically confirmed erosions were found in 10 patients, and were significantly associated with anti-CCP, anti-CarP and RF. Musculoskeletal ultrasonography scores were higher in anti-CCP-positive compared to anti-CCP-negative patients.

    CONCLUSIONS: In the hitherto largest anti-CarP study in SLE, we demonstrate that anti-CarP is more prevalent than anti-CCP and that the overlap is limited. We obtained some evidence that both autoantibodies seem to be associated with erosivity. Similar pathogenetic mechanisms to those seen in RA may be relevant in a subgroup of SLE cases with a phenotype dominated by arthritis.

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  • 5696.
    Ziemssen, Tjalf
    et al.
    Neurol University of Klin Klinikum Carl Gustav Carus, Germany.
    Bajenaru, Ovidiu A.
    Carol Davila University of Medical and Pharm, Romania.
    Carra, Adriana
    Hospital Britanico Buenos Aires, Argentina.
    de Klippel, Nina
    Virga Jessaziekenhuis, Belgium.
    Correia de Sa, Joao
    Hospital Santa Maria, Portugal.
    Edland, Astrid
    Central Hospital Buskerud, Norway.
    Frederiksen, Jette L.
    University of Copenhagen, Denmark.
    Heinzlef, Olivier
    Tenon Hospital, France.
    Karageorgiou, Klimentini E.
    Gen Hospital Athens, Greece.
    Delgado, Rafael H. Lander
    Landtblom, Anne-Marie
    Linköping University, Center for Medical Image Science and Visualization (CMIV). 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 Neurology.
    Macias Islas, Miguel A.
    Central University of Guadalajara, Mexico.
    Tubridy, Niall
    Dublin University, Ireland.
    Gilgun-Sherki, Yossi
    Teva Pharmaceut Ind Ltd, Israel.
    Erratum to: A 2-year observational study of patients with relapsing-remitting multiple sclerosis converting to glatiramer acetate from other disease-modifying therapies: the COPTIMIZE trial2015In: Journal of Neurology, ISSN 0340-5354, E-ISSN 1432-1459, Vol. 262, no 1, p. 248-248Article in journal (Other academic)
    Abstract [en]

    n/a

  • 5697.
    Ziemssen, Tjalf
    et al.
    Klinikum Carl Gustav Carus, Germany.
    Bajenaru, Ovidiu A.
    Carol Davila University of Medical and Pharm, Romania.
    Carra, Adriana
    Hospital Britanico Buenos Aires, Argentina.
    de Klippel, Nina
    Virga Jessaziekenhuis, Belgium.
    de Sa, Joao C.
    Hospital Santa Mari, Belgium.
    Edland, Astrid
    Central Hospital Buskerud, Norway.
    Frederiksen, Jette L.
    University of Copenhagen, Denmark.
    Heinzlef, Olivier
    Hop Tenon, France.
    Karageorgiou, Klimentini E.
    Gen Hospital Athens, Greece.
    Lander Delgado, Rafael H.
    Landtblom, Anne-Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology. Östergötlands Läns Landsting, Local Health Care Services in West Östergötland, Department of Medical Specialist in Motala.
    Macias Islas, Miguel A.
    Central University of Guadalajara, Mexico.
    Tubridy, Niall
    Dublin City University, Ireland.
    Gilgun-Sherki, Yossi
    Teva Pharmaceut Ind Ltd, Israel.
    A 2-year observational study of patients with relapsing-remitting multiple sclerosis converting to glatiramer acetate from other disease-modifying therapies: the COPTIMIZE trial2014In: Journal of Neurology, ISSN 0340-5354, E-ISSN 1432-1459, Vol. 261, no 11, p. 2101-2111Article in journal (Refereed)
    Abstract [en]

    Studies suggest that patients with relapsing-remitting multiple sclerosis (RRMS) who do not benefit from other disease-modifying treatments (DMTs) may benefit from converting to glatiramer acetate (GA). COPTIMIZE was a 24-month observational study designed to assess the disease course of patients converting to GA 20 mg daily from another DMT. Eligible patients had converted to GA and had received prior DMT for 3-6 months, depending on the reasons for conversion. Patients were assessed at baseline and at 6, 12, 18, and 24 months. In total, 672 patients from 148 centers worldwide were included in the analysis. Change of therapy to GA was prompted primarily by lack of efficacy (53.6 %) or intolerable adverse events (AEs; 44.8 %). Over a 24-month period, 72.7 % of patients were relapse free. Mean annual relapse rate decreased from 0.86 [95 % confidence interval (CI) 0.81-0.91] before the change to 0.32 (95 % CI 0.26-0.40; p less than 0.0001) at last observation, while the progression of disability was halted, as the Kurtzke Expanded Disability Status Scale (EDSS) scores remained stable. Patients improved significantly (p less than 0.05) on measures of fatigue, quality of life, depression, and cognition; mobility scores remained stable. The results indicate that changing RRMS patients to GA is associated with positive treatment outcomes.

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  • 5698.
    Zilg, B.
    et al.
    Karolinska Institute, Sweden.
    Bernard, S.
    University of Lyon 1, France.
    Alkass, K.
    Karolinska Institute, Sweden.
    Berg, Sören
    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 Thoracic and Vascular Surgery.
    Druid, H.
    Karolinska Institute, Sweden.
    A new model for the estimation of time of death from vitreous potassium levels corrected for age and temperature2015In: Forensic Science International, ISSN 0379-0738, E-ISSN 1872-6283, Vol. 254, p. 158-166Article in journal (Refereed)
    Abstract [en]

    Analysis of potassium concentration in the vitreous fluid of the eye is frequently used by forensic pathologists to estimate the postmortem interval (PMI), particularly when other methods commonly used in the early phase of an investigation can no longer be applied. The postmortem rise in vitreous potassium has been recognized for several decades and is readily explained by a diffusion of potassium from surrounding cells into the vitreous fluid. However, there is no consensus regarding the mathematical equation that best describes this increase. The existing models assume a linear increase, but different slopes and starting points have been proposed. In this study, vitreous potassium levels, and a number of factors that may influence these levels, were examined in 462 cases with known postmortem intervals that ranged from 2 h to 17 days. We found that the postmortem rise in potassium followed a non-linear curve and that decedent age and ambient temperature influenced the variability by 16% and 5%, respectively. A long duration of agony and a high alcohol level at the time of death contributed less than 1% variability, and evaluation of additional possible factors revealed no detectable impact on the rise of vitreous potassium. Two equations were subsequently generated, one that represents the best fit of the potassium concentrations alone, and a second that represents potassium concentrations with correction for decedent age and/or ambient temperature. The former was associated with narrow confidence intervals in the early postmortem phase, but the intervals gradually increased with longer PMIs. For the latter equation, the confidence intervals were reduced at all PMIs. Therefore, the model that best describes the observed postmortem rise in vitreous potassium levels includes potassium concentration, decedent age, and ambient temperature. Furthermore, the precision of these equations, particularly for long PMIs, is expected to gradually improve by adjusting the constants as more reference data are added over time. A web application that facilitates this calculation process and allows for such future modifications has been developed. (C) 2015 Elsevier Ireland Ltd. All rights reserved.

  • 5699.
    Zimdahl Kahlin, Anna
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Helander, Sara
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Chemistry. Linköping University, Faculty of Medicine and Health Sciences.
    Skoglund, Karin
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Business support and Development, Department of Health and Care Development.
    Söderkvist, Peter
    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, Clinical genetics.
    Mårtensson, Lars-Göran
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Lindqvist Appell, Malin
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Comprehensive study of thiopurine methyltransferase genotype, phenotype, and genotype-phenotype discrepancies in Sweden2019In: Biochemical Pharmacology, ISSN 0006-2952, E-ISSN 1356-1839, Vol. 164, p. 263-272Article in journal (Refereed)
    Abstract [en]

    Thiopurines are widely used in the treatment of leukemia and inflammatory bowel diseases. Thiopurine metabolism varies among individuals because of differences in the polymorphic enzyme thiopurine methyltransferase (TPMT, EC 2.1.1.67), and to avoid severe adverse reactions caused by incorrect dosing it is recommended that the patients TPMT status be determined before the start of thiopurine treatment. This study describes the concordance between genotyping for common TPMT alleles and phenotyping in a Swedish cohort of 12,663 patients sampled before or during thiopurine treatment. The concordance between TPMT genotype and enzyme activity was 94.5%. Compared to the genotype, the first measurement of TPMT enzyme activity was lower than expected for 4.6% of the patients. Sequencing of all coding regions of the TPMT gene in genotype/phenotype discrepant individuals led to the identification of rare and novel TPMT alleles. Fifteen individuals (0.1%) with rare or novel genotypes were identified, and three TPMT alleles (TPMT*42, *43, and *44) are characterized here for the first time. These 15 patients would not have been detected as carrying a deviating TPMT genotype if only genotyping of the most common TPMT variants had been performed. This study highlights the benefit of combining TPMT genotype and phenotype determination in routine testing. More accurate dose recommendations can be made, which might decrease the number of adverse reactions and treatment failures during thiopurine treatment.

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  • 5700.
    Zimmerman, Rosa
    et al.
    University of Buenos Aires.
    Broitman, Esteban
    Linköping University, Department of Physics, Chemistry and Biology, Thin Film Physics. Linköping University, The Institute of Technology. University of Buenos Aires.
    Aplicaciones de las Peliculas Delgadas en Microelectronica1986In: Revista Telegrafica Electronica, ISSN 0035-0516, Vol. 75, no 880, p. 2052-2056Article in journal (Refereed)
    Abstract [es]

    En este articulo se presenta una reseña acerca del uso de las peliculas delgadas en microelectronica con especial enfasis en las peliculas resistivas. Se detallan las propiedades electricas de la aleacion niquel-cromo.

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