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  • 301.
    Gron, Kathrine Lederballe
    et al.
    Rigshosp, Denmark; Rigshosp, Denmark; Univ Copenhagen, Denmark.
    Arkema, Elizabeth V.
    Karolinska Inst, Sweden.
    Glintborg, Bente
    Rigshosp, Denmark; Rigshosp, Denmark; Copenhagen Univ Hosp, Denmark.
    Mehnert, Frank
    Aarhus Univ Hosp, Denmark.
    Ostergaard, Mikkel
    Rigshosp, Denmark; Rigshosp, Denmark; Univ Copenhagen, Denmark.
    Dreyer, Lene
    Aalborg Univ Hosp, Denmark.
    Norgaard, Mette
    Aarhus Univ Hosp, Denmark.
    Krogh, Niels Steen
    ZiteLab ApS, Denmark.
    Askling, Johan
    Karolinska Inst, Sweden.
    Hetland, Merete Lund
    Rigshosp, Denmark; Univ Copenhagen, Denmark.
    Askling, Johan
    Karolinska Inst, Sweden.
    Klareskog, Lars
    Karolinska Inst, Sweden.
    Feltelius, Nils
    Karolinska Inst, Sweden.
    Baecklund, Eva
    Uppsala Univ, Sweden.
    Sjöwall, Christopher
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Reumatologiska kliniken i Östergötland.
    Rantapaa-Dahlqvist, Solbritt
    Umea Univ, Sweden.
    Forsblad-dElia, Helena
    Umea Univ, Sweden.
    Jacobsson, Lennart
    Sahlgrens Acad, Sweden.
    Turesson, Carl
    Lund Univ, Sweden.
    Lindqvist, Elisabet
    Lund Univ, Sweden.
    Nisell, Ralph
    Swedish Rheumatol Qual Register, Sweden.
    Risk of serious infections in patients with rheumatoid arthritis treated in routine care with abatacept, rituximab and tocilizumab in Denmark and Sweden2019Inngår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 78, nr 3, s. 320-327Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective To estimate (1) crude and age-and gender-adjusted incidence rates (IRs) of serious infections (SI) and (2) relative risks (RR) of SI in patients with rheumatoid arthritis (RA) initiating treatment with abatacept, rituximab or tocilizumab in routine care. Methods This is an observational cohort study conducted in parallel in Denmark and Sweden including patients with RA in Denmark (DANBIO) and Sweden (Anti-Rheumatic Treatment in Sweden Register/Swedish Rheumatology Quality Register) who started abatacept/rituximab/tocilizumab in 2010-2015. Patients could contribute to more than one treatment course. Incident SI (hospitalisations listing infection) and potential confounders were identified through linkage to national registries. Age-and gender-adjusted IRs of SI per 100 person years and additionally adjusted RRs of SI during 0-12 and 0-24 months since start of treatment were assessed (Poisson regression). Country-specific RRs were pooled using inverse variance weighting. Results We identified 8987 treatment courses (abatacept: 2725; rituximab: 3363; tocilizumab: 2899). At treatment start, rituximab-treated patients were older, had longer disease duration and more previous malignancies; tocilizumab-treated patients had higher C reactive protein. During 0-12 and 0-24 months of follow-up, 456 and 639 SI events were identified, respectively. The following were the age-and gender-adjusted 12-month IRs for abatacept/rituximab/tocilizumab: 7.1/8.1/6.1 for Denmark and 6.0/6.4/4.7 for Sweden. The 24-month IRs were 6.1/7.5/5.2 for Denmark and 5.6/5.8/4.3 for Sweden. Adjusted 12-month RRs for tocilizumab versus rituximab were 0.82 (0.50 to 1.36) for Denmark and 0.76 (0.57 to 1.02) for Sweden, pooled 0.78 (0.61 to 1.01); for abatacept versus rituximab 0.94 (0.55 to 1.60) for Denmark and 0.86 (0.66 to 1.13) for Sweden, pooled 0.88 (0.69 to 1.12); and for abatacept versus tocilizumab 1.15 (0.69 to 1.90) for Denmark and 1.14 (0.83 to 1.55) for Sweden, pooled 1.13 (0.91 to 1.42). The adjusted RRs for 0-24 months were similar. Conclusion For patients starting abatacept, rituximab or tocilizumab, differences in baseline characteristics were seen. Numerical differences in IR of SI between drugs were observed. RRs seemed to vary with drug (tocilizumab amp;lt; abatacept amp;lt; rituximab) but should be interpreted with caution due to few events and risk of residual confounding.

  • 302.
    Guendouzi, Jacqueline
    et al.
    Southeastern Louisiana University, USA.
    Meaux, A.
    Southeastern Louisiana University, USA.
    Müller, Nicole
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Avoiding interactional conflict in dementia: the influence of gender styles on interactions.2016Inngår i: Journal of Language Aggression and Conflict, ISSN 2213-1272, Vol. 4, nr 1, s. 9-35Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Sociolinguistic research in the general population has established the existence of gender differences in the social use of language. In particular, it has been noted that women use more markers of politeness, small talk and structural devices (e.g. minimal responses, tag questions) to help maintain their conversations. Analysis of interactions involving people with dementia (PWD) suggests that these gender based differences were still present in the face of dementia. Furthermore, the use of these forms of language helped the women with dementia to avoid conflict and extend the length of their interactions. This study investigated whether the use of such language helped or hindered women with dementia in maintaining conversational satisfaction.

  • 303.
    Guldbrand, Hans
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Allmänmedicin. Linköpings universitet, Hälsouniversitetet.
    Dizdar, B.
    Linköpings universitet, Institutionen för medicin och hälsa, Allmänmedicin. Linköpings universitet, Hälsouniversitetet.
    Bunjaku, B.
    Linköpings universitet, Institutionen för medicin och hälsa, Allmänmedicin. Linköpings universitet, Hälsouniversitetet.
    Lindström, Torbjörn
    Linköpings universitet, Institutionen för medicin och hälsa, Internmedicin. Linköpings universitet, Institutionen för medicin och hälsa, Endokrinologi. Linköpings universitet, Hälsouniversitetet.
    Bachrach-Lindström, Margareta
    Linköpings universitet, Institutionen för medicin och hälsa, Omvårdnad. Linköpings universitet, Hälsouniversitetet.
    Fredrikson, Mats
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Hälsouniversitetet.
    Östgren, Carl Johan
    Linköpings universitet, Institutionen för medicin och hälsa, Allmänmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Närsjukvården i västra Östergötland, Primärvården i västra länsdelen.
    Nyström, Fredrik H.
    Linköpings universitet, Institutionen för medicin och hälsa, Internmedicin. Linköpings universitet, Institutionen för medicin och hälsa, Endokrinologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Endokrinmedicinska kliniken.
    In type 2 diabetes, randomisation to advice to follow a low-carbohydrate diet transiently improves glycaemic control compared with advice to follow a low-fat diet producing a similar weight loss2012Inngår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 55, nr 8, s. 2118-2127Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    AIMS/HYPOTHESIS: The study aimed to compare the effects of a 2 year intervention with a low-fat diet (LFD) or a low-carbohydrate diet (LCD), based on four group meetings to achieve compliance. METHODS: This was a prospective randomised parallel trial involving 61 adults with type 2 diabetes consecutively recruited in primary care and randomised by drawing ballots. Patients that did not speak Swedish could not be recruited. The primary outcomes in this non-blinded study were weight and HbA(1c). Patients on the LFD aimed for 55-60 energy per cent (E%) and those on LCD for 20 E% from carbohydrate. RESULTS: The mean BMI and HbA(1c) of the participants were 32.7 ± 5.4 kg/m(2) and 57.0 ± 9.2 mmol/mol, respectively. No patients were lost to follow-up. Weight loss did not differ between groups and was maximal at 6 months: LFD -3.99 ± 4.1 kg (n = 31); LCD -4.31 ± 3.6 kg (n = 30); p < 0.001 within groups. At 24 months, patients on the LFD had lost -2.97 ± 4.9 kg and those on LCD -2.34 ± 5.1 kg compared with baseline (p = 0.002 and p = 0.020 within groups, respectively). HbA(1c) fell in the LCD group only (LCD at 6 months -4.8 ± 8.3 mmol/mol, p = 0.004, at 12 months -2.2 ± 7.7 mmol/mol, p = 0.12; LFD at 6 months -0.9 ± 8.8 mmol/mol, p = 0.56). At 6 months, HDL-cholesterol had increased with the LCD (from 1.13 ± 0.33 mmol/l to 1.25 ± 0.47 mmol/l, p = 0.018) while LDL-cholesterol did not differ between groups. Insulin doses were reduced in the LCD group (0 months, LCD 42 ± 65 E, LFD 39 ± 51 E; 6 months, LCD 30 ± 47 E, LFD 38 ± 48 E; p = 0.046 for between-group change). CONCLUSIONS/INTERPRETATION: Weight changes did not differ between the diet groups, while insulin doses were reduced significantly more with the LCD at 6 months, when compliance was good. Thus, aiming for 20% of energy intake from carbohydrates is safe with respect to cardiovascular risk compared with the traditional LFD and this approach could constitute a treatment alternative. TRIAL REGISTRATION: ClinicalTrials.gov NCT01005498 FUNDING: University Hospital of Linköping Research Funds, Linköping University, the County Council of Östergötland, and the Diabetes Research Centre of Linköping University.

  • 304.
    Gustafsson, Greta
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Neurofysiologiska kliniken US.
    Broström, Anders
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Neurofysiologiska kliniken US. Department of Nursing Science, School of Health Sciences, Jönköping University, Jönköping, Sweden.
    Ulander, Martin
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Neurofysiologiska kliniken US.
    Vrethem, Magnus
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Närsjukvården i centrala Östergötland, Neurologiska kliniken.
    Svanborg, Eva
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Neurofysiologiska kliniken US.
    Occurrence of epileptiform discharges and sleep during EEG recordings in children after melatonin intake versus sleep-deprivation2015Inngår i: Clinical Neurophysiology, ISSN 1388-2457, E-ISSN 1872-8952, Vol. 126, nr 8, s. 1493-1497Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE:

    To determine if melatonin is equally efficient as partial sleep deprivation in inducing sleep without interfering with epileptiform discharges in EEG recordings in children 1-16years old.

    METHODS:

    We retrospectively analysed 129 EEGs recorded after melatonin intake and 113 EEGs recorded after partial sleep deprivation. Comparisons were made concerning occurrence of epileptiform discharges, the number of children who fell asleep and the technical quality of EEG recordings. Comparison between different age groups was also made.

    RESULTS:

    No significant differences were found regarding occurrence of epileptiform discharges (33% after melatonin intake, 36% after sleep deprivation), or proportion of unsuccessful EEGs (8% and 10%, respectively). Melatonin and sleep deprivation were equally efficient in inducing sleep (70% in both groups). Significantly more children aged 1-4years obtained sleep after melatonin intake in comparison to sleep deprivation (82% vs. 58%, p⩽0.01), and in comparison to older children with melatonin induced sleep (58-67%, p⩽0.05). Sleep deprived children 9-12years old had higher percentage of epileptiform discharges (62%, p⩽0.05) compared to younger sleep deprived children.

    CONCLUSION:

    Melatonin is equally efficient as partial sleep deprivation to induce sleep and does not affect the occurrence of epileptiform discharges in the EEG recording. Sleep deprivation could still be preferable in older children as melatonin probably has less sleep inducing effect.

    SIGNIFICANCE:

    Melatonin induced sleep have advantages, especially in younger children as they fall asleep easier than after sleep deprivation. The procedure is easier for the parents than keeping a young child awake for half the night.

  • 305.
    Gustafsson, Håkan
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för radiologiska vetenskaper. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Diagnostikcentrum, Medicinsk teknik i Östergötland. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV.
    Hallbeck, Martin
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk patologi och klinisk genetik.
    Lindgren, Mikael
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska högskolan. Norwegian University of Science and Technology, Norway.
    Kolbun, Natallia
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för radiologiska vetenskaper. Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV.
    Jonson, Maria
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska högskolan.
    Engström, Maria
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för radiologiska vetenskaper. Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV.
    de Muinck, Ebo
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Region Östergötland, Hjärt- och Medicincentrum, Kardiologiska kliniken US.
    Zachrisson, Helene
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Hälsouniversitetet. Region Östergötland, Hjärt- och Medicincentrum, Fysiologiska kliniken US.
    Visualization of oxidative stress in ex vivo biopsies using electron paramagnetic resonance imaging2015Inngår i: Magnetic Resonance in Medicine, ISSN 0740-3194, E-ISSN 1522-2594, Vol. 73, nr 4, s. 1682-1691Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    PURPOSE: The purpose of this study was to develop an X-Band electron paramagnetic resonance imaging protocol for visualization of oxidative stress in biopsies.

    METHODS: The developed electron paramagnetic resonance imaging protocol was based on spin trapping with the cyclic hydroxylamine spin probe 1-hydroxy-3-methoxycarbonyl-2,2,5,5-tetramethylpyrrolidine and X-Band EPR imaging. Computer software was developed for deconvolution and back-projection of the EPR image. A phantom containing radicals of known spatial characteristic was used for evaluation of the developed protocol. As a demonstration of the technique electron paramagnetic resonance imaging of oxidative stress was performed in six sections of atherosclerotic plaques. Histopathological analyses were performed on adjoining sections.

    RESULTS: The developed computer software for deconvolution and back-projection of the EPR images could accurately reproduce the shape of a phantom of known spatial distribution of radicals. The developed protocol could successfully be used to image oxidative stress in six sections of the three ex vivo atherosclerotic plaques.

    CONCLUSIONS: We have shown that oxidative stress can be imaged using a combination of spin trapping with the cyclic hydroxylamine spin probe cyclic hydroxylamine spin probe 1-hydroxy-3-methoxycarbonyl-2,2,5,5-tetramethylpyrrolidine and X-Band EPR imaging. A thorough and systematic evaluation on different types of biopsies must be performed in the future to validate the proposed technique. Magn Reson Med, 2014.

  • 306.
    Gustafsson, Håkan
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för radiologiska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Röntgenkliniken i Norrköping/Finspång. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV.
    Kale, Ajay
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Öron- näsa- och halskliniken US.
    Dasu, Alexandru
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för radiologiska vetenskaper. Linköpings universitet, Medicinska fakulteten. The Skandion Clinic, Uppsala, Sweden.
    Lund, Anders
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemisk Fysik. Linköpings universitet, Tekniska fakulteten.
    Edqvist, Per-Henrik
    Uppsala University, Uppsala, Sweden.
    Roberg, Karin
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Öron- näsa- och halskliniken US.
    EPR oximetry of cetuximab-treated head-and-neck tumours in a mouse model2017Inngår i: Cell Biochemistry and Biophysics, ISSN 1085-9195, E-ISSN 1559-0283, Vol. 75, nr 3-4, s. 299-309Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Head and neck squamous cell carcinoma (HNSCC) tumours are associated with high mortality despite advances in therapy. The monoclonal antibody cetuximab (Erbitux®) has been approved for the treatment of advanced HNSCC. However, only a subset of HNSC patients receiving cetuximab actually responds to treatment, underlining the need for a means to tailor treatments of individual patients. The aim of the present study was to investigate the effect of cetuximab treatment on tumour growth, on tumour partial oxygen pressure as measured by LiPc electron paramagnetic resonance oximetry and on the expression of proteins involved in tumour growth, metabolism and hypoxia. Two HNSCC cell lines, UT-SCC-2 and UT-SCC-14, were used to generate xenografts on female BALB/c (nu/nu) nude mice. Mice with xenografts were given three injections of intraperitoneal cetuximab or phosphate-buffered saline, and the tumour volume was recorded continuously. After treatment the tumour partial oxygen pressure was measured by LiPc electron paramagnetic resonance oximetry and the expression of epidermal growth factor receptor (EGFR), phosphorylated EGFR, Ki-67, MCT1, MCT4, GLUT1, CAIX and HIF-1α were investigated by immunohistochemistry. In xenografts from both cell lines (UT-SCC-2 and UT-SCC-14) cetuximab had effect on the tumour volume but the effect was more pronounced on UT-SCC-14 xenografts. A higher tumour oxygenation was measured in cetuximab-treated tumours from both cell lines compared to untreated controls. Immunocytochemical staining after cetuximab treatment shows a significantly decreased expression of EGFR, pEGFR, Ki67, CAIX and nuclear HIF-1α in UT-SCC-14 tumours compared to untreated controls. MCT1 and GLUT1 were significantly decreased in tumours from both cell lines but more pronounced in UT-SCC-14 tumours. Taken together, our results show that cetuximab treatment decreases the tumour growth and increases the tumour partial oxygen pressure of HNSCC xenografts. Furthermore we found a potential connection between the partial oxygen pressure of the tumours and the expression of proteins involved in tumour growth, metabolism and hypoxia.

  • 307.
    Gustafsson, Mika
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Bioinformatik. Linköpings universitet, Tekniska fakulteten.
    Gawel, Danuta
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten.
    Alfredsson, Lars
    Karolinska Institute, Sweden.
    Baranzini, Sergio
    University of Calif San Francisco, CA, USA.
    Bjorkander, Janne
    County Council Jonköping, Sweden.
    Blomgran, Robert
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    Hellberg, Sandra
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Eklund, Daniel
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Ernerudh, Jan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk immunologi och transfusionsmedicin.
    Kockum, Ingrid
    Karolinska Institute, Sweden; Centre Molecular Med, Sweden.
    Konstantinell, Aelita
    Linköpings universitet, Medicinska fakulteten. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Arctic University of Norway, Norway.
    Lahesmaa, Riita
    University of Turku, Finland; Abo Akad University, Finland.
    Lentini, Antonio
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten.
    Liljenström, H. Robert I.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten.
    Mattson, Lina
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten.
    Matussek, Andreas
    County Council Jonköping, Sweden.
    Mellergård, Johan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Närsjukvården i centrala Östergötland, Neurologiska kliniken.
    Mendez, Melissa
    University of Peruana Cayetano Heredia, Peru.
    Olsson, Tomas
    Karolinska Institute, Sweden; Centre Molecular Med, Sweden.
    Pujana, Miguel A.
    Catalan Institute Oncol, Spain.
    Rasool, Omid
    University of Turku, Finland; Abo Akad University, Finland.
    Serra-Musach, Jordi
    Catalan Institute Oncol, Spain.
    Stenmarker, Margaretha
    County Council Jonköping, Sweden.
    Tripathi, Subhash
    University of Turku, Finland; Abo Akad University, Finland.
    Viitala, Miro
    University of Turku, Finland; Abo Akad University, Finland.
    Wang, Hui
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten. University of Texas MD Anderson Cancer Centre, TX 77030 USA.
    Zhang, Huan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten.
    Nestor, Colm
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten.
    Benson, Mikael
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Allergicentrum US.
    A validated gene regulatory network and GWAS identifies early regulators of T cell-associated diseases2015Inngår i: Science Translational Medicine, ISSN 1946-6234, E-ISSN 1946-6242, Vol. 7, nr 313, artikkel-id 313ra178Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Early regulators of disease may increase understanding of disease mechanisms and serve as markers for presymptomatic diagnosis and treatment. However, early regulators are difficult to identify because patients generally present after they are symptomatic. We hypothesized that early regulators of T cell-associated diseases could be found by identifying upstream transcription factors (TFs) in T cell differentiation and by prioritizing hub TFs that were enriched for disease-associated polymorphisms. A gene regulatory network (GRN) was constructed by time series profiling of the transcriptomes and methylomes of human CD4(+) T cells during in vitro differentiation into four helper T cell lineages, in combination with sequence-based TF binding predictions. The TFs GATA3, MAF, and MYB were identified as early regulators and validated by ChIP-seq (chromatin immunoprecipitation sequencing) and small interfering RNA knockdowns. Differential mRNA expression of the TFs and their targets in T cell-associated diseases supports their clinical relevance. To directly test if the TFs were altered early in disease, T cells from patients with two T cell-mediated diseases, multiple sclerosis and seasonal allergic rhinitis, were analyzed. Strikingly, the TFs were differentially expressed during asymptomatic stages of both diseases, whereas their targets showed altered expression during symptomatic stages. This analytical strategy to identify early regulators of disease by combining GRNs with genome-wide association studies may be generally applicable for functional and clinical studies of early disease development.

  • 308.
    Gustafsson, Mikael
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa.
    Landtblom, Anne-Marie
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Neurologiska kliniken.
    Lundberg, Peter
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för radiologiska vetenskaper. Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Radiofysikavdelningen US.
    Absolut kvantifiering av metaboliter i hjärnans vita substans hos patienter med MS och normal magnetkamerundersökning2000Konferansepaper (Annet vitenskapelig)
  • 309.
    Gutefeldt, Kerstin
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Infektionskliniken i Östergötland.
    Hedman, Christina A
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Endokrinmedicinska kliniken.
    Thyberg, Ingrid S M
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Reumatologiska kliniken i Östergötland.
    Bachrach-Lindström, Margareta
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för omvårdnad. Linköpings universitet, Medicinska fakulteten.
    Arnqvist, Hans
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Endokrinmedicinska kliniken.
    Spångeus, Anna
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Endokrinmedicinska kliniken.
    Upper extremity impairments in type 1 diabetes with long duration: common problems with great impact on daily life2019Inngår i: Disability and Rehabilitation, ISSN 0963-8288, E-ISSN 1464-5165, Vol. 41, nr 6, s. 633-640Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    PURPOSE: To investigate the prevalence, activity limitations and potential risk factors of upper extremity impairments in type 1 diabetes in comparison to controls.

    METHODS: In a cross-sectional population-based study in the southeast of Sweden, patients with type 1 diabetes <35 years at onset, duration ≥20 years, <67 years old and matched controls were invited to answer a questionnaire on upper extremity impairments and activity limitations and to take blood samples.

    RESULTS: Seven hundred and seventy-three patients (ages 50 ± 10 years, diabetes duration 35 ± 10 years) and 708 controls (ages 54 ± 9 years) were included. Shoulder pain and stiffness, hand paraesthesia and finger impairments were common in patients with a prevalence of 28-48%, which was 2-4-folds higher than in controls. Compared to controls, the patients had more bilateral impairments, often had coexistence of several upper extremity impairments, and in the presence of impairments, reported more pronounced activity limitations. Female gender (1.72 (1.066-2.272), p = 0.014), longer duration (1.046 (1.015-1.077), p = 0.003), higher body mass index (1.08 (1.017-1.147), p = 0.013) and HbA1c (1.029 (1.008-1.05), p = 0.007) were associated with upper extremity impairments.

    CONCLUSIONS: Compared to controls, patients with type 1 diabetes have a high prevalence of upper extremity impairments, often bilateral, which are strongly associated with activity limitations. Recognising these in clinical practise is crucial, and improved preventative, therapeutic and rehabilitative interventions are needed. Implications for rehabilitation Upper extremity impairments affecting the shoulder, hand and fingers are common in patients with type 1 diabetes, the prevalence being 2-4-fold higher compared to non-diabetic persons. Patients with diabetes type 1 with upper extremity impairments have more pronounced limitations in daily activities compared to controls with similar impairments. Recognising upper extremity impairments and activity limitations are important and improved preventive, therapeutic and rehabilitation methods are needed.

  • 310.
    Gutefeldt, Kerstin
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Endokrinmedicinska kliniken.
    Hedman, Christina
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Endokrinmedicinska kliniken.
    Thyberg, Ingrid
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Reumatologiska kliniken i Östergötland.
    Bachrach Lindström, Margareta
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för omvårdnad. Linköpings universitet, Medicinska fakulteten.
    Spångeus, Anna
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Endokrinmedicinska kliniken.
    Arnqvist, Hans
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Endokrinmedicinska kliniken.
    Dysregulated growth hormone-insulin-like growth factor-1 axis in adult type 1 diabetes with long duration2018Inngår i: Clinical Endocrinology, ISSN 0300-0664, E-ISSN 1365-2265, Vol. 89, nr 4, s. 424-430Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    ContextIn type 1 diabetes (T1D), dysregulation of the GH-IGF-1 axis has been reported. Whether this is related to upper extremity impairments (UEI) is unknown. ObjectiveExamine differences in GH-IGF-1 axis between T1D on subcutaneous insulin treatment and matched controls without diabetes and possible associations between GH-IGF-1 axis and UEI. DesignCross-sectional population-based study. Patients with T1D, onset amp;lt;35years, duration 20years, amp;lt;67years old and controls were invited to answer questionnaires and take blood samples. SubjectsA total of 605 patients with T1D and 533 controls accepted to participate. OutcomesFasting levels of IGF-1, IGF-1 Z-score, IGFBP-1, IGFBP-3, C-peptide, GH and UEI. ResultsPatients with T1D had lower IGF-1 and IGFBP-3 and higher IGFBP-1 and GH than controls. The difference in IGF-1 persisted with age. Insulin dose was associated with increasing IGF-1 Z-score but even at a very high insulin dose (amp;gt;1U/kg) IGF-1 Z-score was subnormal compared to controls. IGF-1 Z-score was unaffected by glycaemic control (HbA1c) but increased with residual insulin secretion, (C-peptide 1-99 pmol/L). IGFBP-1 was associated with fasting blood glucose, negatively in controls and positively in patients with T1D probably reflecting insulin resistance and insulin deficiency, respectively. There was no association between lower IGF-1 Z-score and UEI in T1D. ConclusionIn adult T1D with fair glycaemic control, the GH-IGF-1 axis is dysregulated exhibiting GH resistance, low IGF-1 and elevated IGFBP-1. Subcutaneous insulin cannot normalize these changes while endogenous insulin secretion has marked effects on IGF-1 pointing to a role of portal insulin.

  • 311.
    Guterstam, Arvid
    et al.
    Karolinska Institute, Sweden.
    Björnsdotter Åberg, Malin
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Karolinska Institute, Sweden.
    Bergouignan, Loretxu
    Karolinska Institute, Sweden; Basque Centre Cognit Brain and Language, Spain.
    Gentile, Giovanni
    Karolinska Institute, Sweden; CALTECH, CA 91125 USA.
    Li, Tie-Qiang
    Karolinska University, Sweden.
    Henrik Ehrsson, H.
    Karolinska Institute, Sweden.
    Decoding illusory self-location from activity in the human hippocampus2015Inngår i: Frontiers in Human Neuroscience, ISSN 1662-5161, E-ISSN 1662-5161, Vol. 9, nr 412Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Decades of research have demonstrated a role for the hippocampus in spatial navigation and episodic and spatial memory. However, empirical evidence linking hippocampal activity to the perceptual experience of being physically located at a particular place in the environment is lacking. In this study, we used a multisensory out-of-body illusion to perceptually teleport six healthy participants between two different locations in the scanner room during high-resolution functional magnetic resonance imaging (fMRI). The participants were fitted with MRI-compatible head-mounted displays that changed their first-person visual perspective to that of a pair of cameras placed in one of two corners of the scanner room. To elicit the illusion of being physically located in this position, we delivered synchronous visuo-tactile stimulation in the form of an object moving toward the cameras coupled with touches applied to the participants chest. Asynchronous visuo-tactile stimulation did not induce the illusion and served as a control condition. We found that illusory self-location could be successfully decoded from patterns of activity in the hippocampus in all of the participants in the synchronous (P less than 0.05) but not in the asynchronous condition (Pgreater than 0.05). At the group-level, the decoding accuracy was significantly higher in the synchronous than in the asynchronous condition (P = 0.012). These findings associate hippocampal activity with the perceived location of the bodily self in space, which suggests that the human hippocampus is involved not only in spatial navigation and memory but also in the construction of our sense of bodily self-location.

  • 312.
    Guterstam, Arvid
    et al.
    Karolinska Institute, Sweden.
    Björnsdotter Åberg, Malin
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Karolinska Institute, Sweden.
    Gentile, Giovanni
    Karolinska Institute, Sweden.
    Ehrsson, H. Henrik
    Karolinska Institute, Sweden.
    Posterior Cingulate Cortex Integrates the Senses of Self-Location and Body Ownership2015Inngår i: Current Biology, ISSN 0960-9822, E-ISSN 1879-0445, Vol. 25, nr 11, s. 1416-1425Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The senses of owning a body and being localized somewhere in space are two key components of human self-consciousness. Despite a wealth of neurophysiological and neuroimaging research on the representations of the spatial environment in the parietal and medial temporal cortices, the relationship between body ownership and self-location remains unexplored. To investigate this relationship, we used a multisensory out-of-body illusion to manipulate healthy participants perceived self-location, head direction, and sense of body ownership during high-resolution fMRI. Activity patterns in the hippocampus and the posterior cingulate, retrosplenial, and intraparietal cortices reflected the sense of self-location, whereas the sense of body ownership was associated with premotor-intraparietal activity. The functional interplay between these two sets of areas was mediated by the posterior cingulate cortex. These results extend our understanding of the role of the posterior parietal and medial temporal cortices in spatial cognition by demonstrating that these areas not only are important for ecological behaviors, such as navigation and perspective taking, but also support the perceptual representation of the bodily self in space. Our results further suggest that the posterior cingulate cortex has a key role in integrating the neural representations of self-location and body ownership.

  • 313.
    Gyllemark, Paula
    et al.
    Department of Infectious Diseases, Region Jönköping County, Jönköping, Sweden.
    Forsberg, Pia
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Infektionskliniken i Östergötland.
    Ernerudh, Jan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk immunologi och transfusionsmedicin.
    Henningsson, Anna J.
    Clinical Microbiology, Division of Medical Services, Jönköping, Region Jönköping County, Sweden.
    Intrathecal Th17- and B cell-associated cytokine and chemokine responses in relation to clinical outcome in Lyme neuroborreliosis: a large retrospective study.2017Inngår i: Journal of Neuroinflammation, ISSN 1742-2094, E-ISSN 1742-2094, Vol. 14, nr 1Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: B cell immunity, including the chemokine CXCL13, has an established role in Lyme neuroborreliosis, and also, T helper (Th) 17 immunity, including IL-17A, has recently been implicated.

    METHODS: We analysed a set of cytokines and chemokines associated with B cell and Th17 immunity in cerebrospinal fluid and serum from clinically well-characterized patients with definite Lyme neuroborreliosis (group 1, n = 49), defined by both cerebrospinal fluid pleocytosis and Borrelia-specific antibodies in cerebrospinal fluid and from two groups with possible Lyme neuroborreliosis, showing either pleocytosis (group 2, n = 14) or Borrelia-specific antibodies in cerebrospinal fluid (group 3, n = 14). A non-Lyme neuroborreliosis reference group consisted of 88 patients lacking pleocytosis and Borrelia-specific antibodies in serum and cerebrospinal fluid.

    RESULTS: Cerebrospinal fluid levels of B cell-associated markers (CXCL13, APRIL and BAFF) were significantly elevated in groups 1, 2 and 3 compared with the reference group, except for BAFF, which was not elevated in group 3. Regarding Th17-associated markers (IL-17A, CXCL1 and CCL20), CCL20 in cerebrospinal fluid was significantly elevated in groups 1, 2 and 3 compared with the reference group, while IL-17A and CXCL1 were elevated in group 1. Patients with time of recovery <3 months had lower cerebrospinal fluid levels of IL-17A, APRIL and BAFF compared to patients with recovery >3 months.

    CONCLUSIONS: By using a set of markers in addition to CXCL13 and IL-17A, we confirm that B cell- and Th17-associated immune responses are involved in Lyme neuroborreliosis pathogenesis with different patterns in subgroups. Furthermore, IL-17A, APRIL and BAFF may be associated with time to recovery after treatment.

  • 314.
    Göransson, Nathanael
    et al.
    Linköpings universitet, Institutionen för medicinsk teknik, Avdelningen för medicinsk teknik. Linköpings universitet, Tekniska fakulteten.
    Johansson, Johannes
    Linköpings universitet, Institutionen för medicinsk teknik, Avdelningen för medicinsk teknik. Linköpings universitet, Tekniska fakulteten.
    Alonso, Fabiola
    Linköpings universitet, Institutionen för medicinsk teknik, Avdelningen för medicinsk teknik. Linköpings universitet, Tekniska fakulteten.
    Wårdell, Karin
    Linköpings universitet, Institutionen för medicinsk teknik, Avdelningen för medicinsk teknik. Linköpings universitet, Tekniska fakulteten.
    Zsigmond, Peter
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Neurokirurgiska kliniken US.
    Postoperative lead movement after deep brain stimulation surgery and changes of stimulation area2017Konferansepaper (Annet vitenskapelig)
    Abstract [en]

    Introduction

    Lead movement after deep brain stimulation (DBS) may occur and influence the area of stimulation. The cause of the displacement is not fully understood. The aim of the study was to investigate differences in lead position between the day after surgery and approximately one month postoperatively and also simulate the electric field (EF) around the active contacts.

    Methods

    23 patients with movement disorders underwent DBS surgery (37 leads). CT at the two time points were co-fused respectively with the stereotactic images in Surgiplan. The coordinates (x, y, z) of the lead tips were compared between the two dates (paired t-test). 8 of these patients were selected for the EF simulation in Comsol Multiphysics.

    Results

    There was a significant discrepancy (mean ± s.d.) on the left lead: x (0.44 ± 0.72, p < 0.01), y (0.64 ± 0.54, p < 0.001), z (0.62 ± 0.71, p < 0.001).  On the right lead, corresponding values were: x (-0.11 ± 0.61, n.s.), y (0.71 ± 0.54, p < 0.001), z (0.49 ± 0.81, p < 0.05).  No correlation was found between bilateral (n =14) vs. unilateral DBS, gender (n = 17 male) and age < 60 years (n = 8).  The lead movement affected the EF spread (Fig. 1).

    Conclusion

    The left lead tip displayed a tendency to move lateral, anterior and inferior and the right a tendency to move anterior and inferior. Lead movement after DBS can be a factor to consider before starting the stimulation. The differences in the area of stimulation might affect clinical outcome.

  • 315.
    Hadizadeh, Fatemeh
    et al.
    Karolinska Inst, Sweden; Isfahan Univ Med Sci, Iran.
    Bonfiglio, Ferdinando
    Karolinska Inst, Sweden; BioDonostia Hlth Res Inst, Spain.
    Belheouane, Meriem
    Christian Albrechts Univ Kiel, Germany; Max Planck Inst Evolutionary Biol, Germany.
    Vallier, Marie
    Christian Albrechts Univ Kiel, Germany; Max Planck Inst Evolutionary Biol, Germany.
    Sauer, Sascha
    Max Delbruck Ctr Mol Med BIMSB BIH, Germany.
    Bang, Corinna
    Christian Albrechts Univ Kiel, Germany.
    Bujanda, Luis
    BioDonostia Hlth Res Inst, Spain; Univ Pais Vasco UPV EHU, Spain.
    Andreasson, Anna
    Karolinska Inst, Sweden; Stockholm Univ, Sweden.
    Agreus, Lars
    Karolinska Inst, Sweden.
    Engstrand, Lars
    Karolinska Inst, Sweden; Sci Life Lab, Sweden.
    Talley, Nicholas J.
    Karolinska Inst, Sweden; Univ Newcastle, Australia; Mayo Clin, MN USA; AGIRA, Australia.
    Rafter, Joseph
    Karolinska Inst, Sweden.
    Baines, John F.
    Christian Albrechts Univ Kiel, Germany; Max Planck Inst Evolutionary Biol, Germany.
    Walter, Susanna
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Magtarmmedicinska kliniken.
    Franke, Andre
    Christian Albrechts Univ Kiel, Germany.
    DAmato, Mauro
    BioDonostia Hlth Res Inst, Spain; Karolinska Inst, Sweden; Basque Sci Fdn, Spain.
    Faecal microbiota composition associates with abdominal pain in the general population2018Inngår i: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 67, nr 4, s. 778-+Artikkel i tidsskrift (Annet vitenskapelig)
    Abstract [en]

    n/a

  • 316.
    Hadizadeh, Fatemeh
    et al.
    Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden; School of Nutrition, Isfahan University of Medical Sciences, Isfahan, Iran.
    Walter, Susanna
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Magtarmmedicinska kliniken.
    Belheouane, Meriem
    Max Planck Institute for Evolutionary Biology, Plön, Germany; Institute for Experimental Medicine, Christian-Albrechts-University of Kiel, Kiel, Germany.
    Bonfiglio, Ferdinando
    Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden.
    Heinsen, Femke-Anouska
    Institute of Clinical Molecular Biology, Kiel University, Kiel, Germany.
    Andreasson, Anna
    Division for Family Medicine, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden; Stress Research Institute, Stockholm University, Stockholm, Sweden.
    Agreus, Lars
    Division for Family Medicine, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.
    Engstrand, Lars
    Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden; Clinical Genomics Facility, Science for Life Laboratory, Stockholm, Sweden.
    Baines, John F
    Max Planck Institute for Evolutionary Biology, Plön, Germany; Institute for Experimental Medicine, Christian-Albrechts-University of Kiel, Kiel, Germany.
    Rafter, Joseph
    Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden.
    Franke, Andre
    Institute of Clinical Molecular Biology, Kiel University, Kiel, Germany.
    DAmato, Mauro
    Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden; BioCruces Health Research Institute and IKERBASQUE, Basque Foundation for Science, Bilbao, Spain.
    Stool frequency is associated with gut microbiota composition2017Inngår i: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 66, nr 3, s. 559-560Artikkel i tidsskrift (Annet vitenskapelig)
  • 317.
    Haglund, Felix
    et al.
    Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
    Garvin, Stina
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk patologi och klinisk genetik.
    Ihre-Lundgren, Catharina
    Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
    Nilsson, Inga-Lena
    Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
    Hall, Evelina
    Karolinska University Hospital, Sweden.
    Carling, Tobias
    Yale School Med, CT USA.
    Hoog, Anders
    Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
    Christofer Juhlin, C.
    Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
    Detailed Lymph Node Sectioning of Papillary Thyroid Carcinoma Specimen Increases the Number of pN1a Patients2016Inngår i: Endocrine pathology, ISSN 1046-3976, E-ISSN 1559-0097, Vol. 27, nr 4, s. 346-351Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Papillary thyroid carcinoma (PTC) is a common endocrine malignancy, frequently presenting with lymph node metastasis at the time of diagnosis. Lymph node staging (N) partly determines treatment, follow-up, and prognosis. Since 2011, our institution has employed a more comprehensive histopathological work-up of lymph nodes in patients with PTC. We sought to retrospectively determine the value of serial lymph node level sectioning in PTCs with negative preoperative lymph node status (pN0) as a method to increase the sensitivity of detecting metastatic disease. We included all patients that underwent thyroidectomy and central neck dissection and subsequent comprehensive lymph node level sectioning due to PTC with an initial pN0 status between the years 2011 and 2015 at our institution. Sixty-seven cases of PTC with a median of 10 metastatic free lymph nodes identified per case were included. After serial lymph node sectioning of the central compartment, 11 cases (16 %) revealed lymph node metastasis, six of which (55 %) presented with a small primary tumor (amp;lt; 20 mm, T1). Of all T1 tumors with initial pN0 status, 18 % (T1a) and 9 % (T1b) reached a pN1 stage after comprehensive lymph node sectioning. Cases with altered lymph node status had a median of 15 identified lymph nodes as compared to ten in cases that remained negative. We conclude that comprehensive lymph node sectioning increased the sensitivity of detecting metastases in PTC and altered the pathological TNM staging (pTNM) for a significant number of patients. Although of limited prognostic significance, the method should be considered as an adjunct tool when assessing lymph node status of PTC as a part of the routine histological work-up to ensure an accurate cancer staging.

  • 318.
    Haj Hosseini, Neda
    et al.
    Linköpings universitet, Institutionen för medicinsk teknik, Biomedicinsk instrumentteknik. Linköpings universitet, Tekniska högskolan.
    Richter, Johan
    Östergötlands Läns Landsting, Rekonstruktionscentrum, Neurokirurgiska kliniken US. Linköpings universitet, Institutionen för medicinsk teknik. Linköpings universitet, Medicinska fakulteten.
    Milos, Peter
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Neurokirurgiska kliniken US. Neurokirurgi.
    Hallbeck, Martin
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelning för neurobiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk patologi och klinisk genetik.
    Wårdell, Karin
    Linköpings universitet, Institutionen för medicinsk teknik, Avdelningen för medicinsk teknik. Linköpings universitet, Medicinska fakulteten. Linköpings universitet, Institutionen för medicinsk teknik, Biomedicinsk instrumentteknik.
    Optical Guidance for Brain Tumor Stereotactic Biopsy2017Konferansepaper (Fagfellevurdert)
  • 319.
    Haj-Hosseini, Neda
    et al.
    Linköpings universitet, Institutionen för medicinsk teknik, Biomedicinsk instrumentteknik. Linköpings universitet, Tekniska fakulteten.
    Milos, Peter
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Neurokirurgiska kliniken US.
    Hildesjö, Camilla
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk patologi och klinisk genetik.
    Hallbeck, Martin
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk patologi och klinisk genetik.
    Richter, Johan
    Linköpings universitet, Institutionen för medicinsk teknik, Biomedicinsk instrumentteknik. Linköpings universitet, Tekniska fakulteten. Region Östergötland, Sinnescentrum, Neurokirurgiska kliniken US.
    Wårdell, Karin
    Linköpings universitet, Institutionen för medicinsk teknik, Biomedicinsk instrumentteknik. Linköpings universitet, Tekniska fakulteten.
    Fluorescence spectroscopy and optical coherence tomography for brain tumor detection2016Konferansepaper (Fagfellevurdert)
    Abstract [en]

    Resection of brain tumor is a challenging task as the tumor does not have clear borders and the malignant types specifically have often a diffuse and infiltrative pattern of growth. Recently, neurosurgical microscopes have been modified to incorporate fluorescence modules for detection of tumor when 5-aminolevulinic acid (5-ALA) is used as a contrast. We have in combination with the fluorescence microscopes implemented and evaluated a fluorescence spectroscopy based handheld probe for detecting the 5-aminolevulinic acid (ALA) induced protoporphyrin IX (PpIX) in the gliomas in 50 patients intraoperatively. The results show a significantly high sensitivity for differentiating tumor from the healthy tissue and distinguished fluorescence intensity levels in the tumor cell infiltration zone around the tumor. However, knowledge on association of the quantified fluorescence signals specifically in the intermediate inflammatory zone with the infiltrative tumor cells can be complemented with volumetric tissue imaging and a higher precision histopathological analysis. In this work, a spectral domain optical coherence tomography (OCT) system with central wavelength of 1325nm has been used to image the tissue volume that the fluorescence is collected from and is evaluated against histopathological analysis for a higher precision slicing. The results show that although healthy brain has a homogenous microstructure in the OCT images, the brain tumor shows a distinguished texture in the images correlated with the PpIX fluorescence intensity and histopathology.

  • 320.
    Haj-Hosseini, Neda
    et al.
    Linköpings universitet, Institutionen för medicinsk teknik, Biomedicinsk instrumentteknik. Linköpings universitet, Tekniska fakulteten.
    Milos, Peter
    Region Östergötland, Sinnescentrum, Neurokirurgiska kliniken US. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Richter, Johan
    Linköpings universitet, Institutionen för medicinsk teknik. Region Östergötland, Sinnescentrum, Neurokirurgiska kliniken US. Linköpings universitet, Tekniska fakulteten.
    Hallbeck, Martin
    Region Östergötland, Diagnostikcentrum, Klinisk patologi och klinisk genetik. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Wårdell, Karin
    Linköpings universitet, Institutionen för medicinsk teknik, Biomedicinsk instrumentteknik. Linköpings universitet, Tekniska fakulteten.
    A Multipurpose Guidance Probe for Stereotactic Biopsy Procedures2016Konferansepaper (Fagfellevurdert)
  • 321.
    Haj-Hosseini, Neda
    et al.
    Linköpings universitet, Tekniska högskolan. Linköpings universitet, Institutionen för medicinsk teknik, Biomedicinsk instrumentteknik.
    Milos, Peter
    Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Kirurgiska kliniken US.
    Richter, Johan
    Linköpings universitet, Institutionen för medicinsk teknik, Biomedicinsk instrumentteknik. Linköpings universitet, Tekniska fakulteten. Region Östergötland, Sinnescentrum, Neurokirurgiska kliniken US.
    Hildesjö, Camilla
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten.
    Hallbeck, Martin
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk patologi och klinisk genetik.
    Wårdell, Karin
    Linköpings universitet, Institutionen för medicinsk teknik, Biomedicinsk instrumentteknik. Linköpings universitet, Tekniska fakulteten.
    Detection of brain tumor using fluorescence and optical coherence tomography2015Konferansepaper (Fagfellevurdert)
    Abstract [en]

    Resection of brain tumor is a challenging task as the tumor does not have clear borders and the malignant types specifically have often a diffuse and infiltrative pattern of growth. We have previously implemented and evaluated a fluorescence spectroscopy based handheld probe for detecting the 5-aminolevulinic acid induced protoporphyrin IX (PpIX) in the gliomas. To add another dimension to the brain tumor detection and volumetric analysis of the tissue that exhibits fluorescence, optical coherence tomography was investigated on tumor specimens.

    Material and Methods:

    A fluorescence microscopy and a spectroscopy system as reported previously were used for detecting the fluorescence signals [1, 2]. A total of 50 patients have been included for intraoperative assessment of the tumor borders using the fluorescence techniques. A spectral domain OCT imaging system (TELESTO II, Thorlabs, Inc., NJ, USA) with central wavelength of 1325 nm was used to study the tissue microstructure post operatively. The system has a resolution of 13 and 5.5 μm in the lateral and axial directions, respectively. Tissue specimens from three patients undergoing brain tumor surgery were studied using the OCT system.

    Results and Conclusion:

    Using fluorescence spectroscopy the tumor could be detected with a sensitivity of 0.84 which was significantly higher than that of the surgical microscope (0.30). Brain tissue appeared rather homogeneous in the OCT images however the highly malignant tissue showed a clear structural difference from the non-malignant or low malignant brain tumor tissue which could be related to the fluorescence signal intensities.

  • 322.
    Haj-Hosseini, Neda
    et al.
    Linköpings universitet, Institutionen för medicinsk teknik, Avdelningen för medicinsk teknik. Linköpings universitet, Tekniska fakulteten.
    Richter, Johan
    Linköpings universitet, Institutionen för medicinsk teknik. Linköpings universitet, Tekniska fakulteten. Region Östergötland, Sinnescentrum, Neurokirurgiska kliniken US.
    Hallbeck, Martin
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelning för neurobiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk patologi.
    Milos, Peter
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Neurokirurgiska kliniken US.
    Wårdell, Karin
    Linköpings universitet, Institutionen för medicinsk teknik, Avdelningen för medicinsk teknik. Linköpings universitet, Tekniska fakulteten.
    Stereotactic Brain Tumor Optical Biopsy2018Konferansepaper (Annet vitenskapelig)
    Abstract [en]

    To provide guidance for targeting diagnostic tumor tissue and to avoid vessel rupture during the biopsy procedure an application specific fiber optic probe was devel-oped. The setup incorporated an in-house developed fluorescence spectroscopy system for 5-aminolevulinic acid (5-ALA) induced protopophyrin IX (PpIX) for detection in the tumor, and laser Doppler flowmeter (LDF) system for measurement of blood perfusion. Fluorescence and blood flow were recorded millimeter-wise towards the pre-calculated target. In conclusion, the optical probe made real-time detection of tumor possible and has a potential for vessel detection during the biopsy procedures. Moreover, the PpIX fluorescence, autofluorescence and blood flow in the tumor could be studied at precise positions in the brain and the tumor. In the next step, further anal-ysis will be added.

  • 323.
    Haj-Hosseini, Neda
    et al.
    Linköpings universitet, Tekniska högskolan. Linköpings universitet, Institutionen för medicinsk teknik, Biomedicinsk instrumentteknik.
    Richter, Johan
    Linköpings universitet, Institutionen för medicinsk teknik, Biomedicinsk instrumentteknik. Linköpings universitet, Tekniska fakulteten. Region Östergötland, Sinnescentrum, Neurokirurgiska kliniken US.
    Hallbeck, Martin
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk patologi och klinisk genetik.
    Wårdell, Karin
    Linköpings universitet, Institutionen för medicinsk teknik, Biomedicinsk instrumentteknik. Linköpings universitet, Tekniska högskolan.
    Low dose 5-aminolevulinic acid: Implications in spectroscopic measurements during brain tumor surgery2015Inngår i: Photodiagnosis and Photodynamic Therapy, ISSN 1572-1000, E-ISSN 1873-1597, Vol. 12, nr 2, s. 209-214Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background

    Using 5-aminolevulinic acid (ALA) as an intraoperative fluorescence contrast has been proven to improve the resection of glioblastoma and contribute to prolonged patient survival. ALA accumulates as protoporphyrin IX (PpIX) in the tumor cells and is administered in an advised dose of 20 mg/kg body weight (b.w.) for brain tumor resection using fluorescence surgical microscopes. PpIX fluorescence availability and intensities of a four folds lower ALA dose (5 mg/kg b.w.) has been investigated in glioblastomas and skin using a spectroscopy system adapted for surgical guidance.

    Methods

    A total of 30 adult patients diagnosed with high grade gliomas were included in the analysis. ALA was orally administered in doses of 5 mg/kg b.w. (n = 15) dissolved in orange juice or 20 mg/kg b.w. (n = 15) dissolved in water. A fluorescence spectroscopy system with a handheld fiber-optical probe was used for performing the quantitative fluorescence measurements.

    Results

    The binominal comparison of the diagnostic performance parameters showed no significant statistical difference (p > 0.05). The median fluorescence values in tumor were 2-3 times higher for the high ALA dose group. No PpIX was detected in the skin of the patients in the low dose group (0/4) while PpIX was detected in the skin of the majority of the patients in the high ALA dose group (13/14).

    Conclusions

    Application of 5 mg/kg ALA was evaluated as equally reliable as the higher dose regarding the diagnostic performance when guidance was performed using a spectroscopic system. Moreover, no PpIX was detected in the skin of the patients.

  • 324.
    Haj-Hosseini, Neda
    et al.
    Linköpings universitet, Institutionen för medicinsk teknik, Avdelningen för medicinsk teknik. Linköpings universitet, Tekniska fakulteten.
    Richter, Johan
    Linköpings universitet, Institutionen för medicinsk teknik. Linköpings universitet, Tekniska fakulteten. Region Östergötland, Sinnescentrum, Neurokirurgiska kliniken US.
    Milos, Peter
    Region Östergötland, Sinnescentrum, Neurokirurgiska kliniken US. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Hallbeck, Martin
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelning för neurobiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk patologi.
    Wårdell, Karin
    Linköpings universitet, Institutionen för medicinsk teknik, Avdelningen för medicinsk teknik. Linköpings universitet, Tekniska fakulteten.
    5-ALA fluorescence and laser Doppler flowmetry for guidance in a stereotactic brain tumor biopsy2018Inngår i: Biomedical Optics Express, E-ISSN 2156-7085, Vol. 9, nr 5, s. 2284-2296Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    A fiber optic probe was developed for guidance during stereotactic brain biopsy procedures to target tumor tissue and reduce the risk of hemorrhage. The probe was connected to a setup for the measurement of 5-aminolevulinic acid (5-ALA) induced fluorescence and microvascular blood flow. Along three stereotactic trajectories, fluorescence (n = 109) and laser Doppler flowmetry (LDF) (n = 144) measurements were done in millimeter increments. The recorded signals were compared to histopathology and radiology images. The median ratio of protoporphyrin IX (PpIX) fluorescence and autofluorescence (AF) in the tumor was considerably higher than the marginal zone (17.3 vs 0.9). The blood flow showed two high spots (3%) in total. The proposed setup allows simultaneous and real-time detection of tumor tissue and microvascular blood flow for tracking the vessels.

  • 325.
    Haj-Hosseini, Neda
    et al.
    Linköpings universitet, Institutionen för medicinsk teknik, Biomedicinsk instrumentteknik. Linköpings universitet, Medicinska fakulteten.
    Richter, Johan
    Linköpings universitet, Institutionen för medicinsk teknik. Linköpings universitet, Tekniska fakulteten.
    Milos, Peter
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Neurokirurgiska kliniken US.
    Hallbeck, Martin
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk patologi och klinisk genetik.
    Wårdell, Karin
    Linköpings universitet, Institutionen för medicinsk teknik, Biomedicinsk instrumentteknik. Linköpings universitet, Tekniska fakulteten.
    Optical guidance for stereotactic brain tumor biopsy procedures-preliminary clinical evaluation2017Konferansepaper (Fagfellevurdert)
    Abstract [en]

    During stereotactic biopsy on suspected tumors in the brain, tissue samples are harvested to determine the malignancy. To provide guidance for finding the diagnostic tumor sites and to avoid vessel rupture, an application specific probe was developed. The setup incorporated spectroscopy for detection of 5-aminolevulinic acid induced protoporphyrin (PpIX) fluorescence and blood flow using laser Doppler flowmetry. The PpIX fluorescence was significantly different in the tumor compared to the gliotic marginal zone (p < 0.05). In conclusion, the systems made real-time tumor detection and vessel tracking possible. Moreover, the autofluorescence and blood perfusion could be studied in the tumor.

  • 326.
    Hales, B. J.
    et al.
    University of Western Australia, Australia.
    Hizawa, N.
    University of Tsukuba, Japan.
    Jenmalm, Maria
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Sverremark-Ekstroem, E.
    Stockholm University, Sweden.
    Wardlaw, A. J.
    University of Leicester, England; Leicester NHS Trust, England.
    Developments in the field of allergy in 2014 through the eyes of Clinical and Experimental Allergy2015Inngår i: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 45, nr 12, s. 1723-1745Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    The pathogenesis of asthma continues to be a major topic of interest to our authors with reviews and original papers on the role of viruses, mechanisms of inflammation, biomarkers, and phenotypes of asthma being major topics. A number of papers described new treatments for asthma focusing on blocking the Th2 response reflecting the fact that two decades of work in this area is finally bearing fruit. The pathogenesis of chronic rhinosinusitis is a growing area of interest, but there has been less on the genetics of airways disease than in previous years possibly reflecting the degree of rigour (and therefore a smaller body of work), with which these sorts of studies are now being undertaken. There continues to be a wide range of papers dealing with mechanisms of allergic disease ranging from clinical-based studies to basic research and the use of in vivo animal models especially mice. As before, mechanisms and new approaches to immunotherapy are common themes. Several were published in the allergens section investigating modification of allergens to increase their effectiveness and reduce the risk of adverse events. Risk factors for allergic disease was a common theme in the epidemiology section and food allergy a common theme in clinical allergy with papers on the development of protocols to induce tolerance and attempts to find biomarkers to distinguish sensitization from allergic disease. This was another exciting year for the editors, and we hope the readers of the journal.

  • 327.
    Hallert, Eva
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för hälso- och sjukvårdsanalys. Linköpings universitet, Hälsouniversitetet.
    Husberg, Magnus
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för hälso- och sjukvårdsanalys. Linköpings universitet, Hälsouniversitetet.
    Kalkan, Almina
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för hälso- och sjukvårdsanalys. Linköpings universitet, Hälsouniversitetet.
    Rahmqvist, Mikael
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för hälso- och sjukvårdsanalys. Linköpings universitet, Hälsouniversitetet.
    Skogh, Thomas
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Reumatologiska kliniken i Östergötland.
    Bernfort, Lars
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för hälso- och sjukvårdsanalys. Linköpings universitet, Hälsouniversitetet. Region Östergötland, Hjärt- och Medicincentrum, Allergicentrum US.
    Changes in sociodemographic characteristics at baseline in two Swedish cohorts of patients with early rheumatoid arthritis diagnosed 1996-98 and 2006-092015Inngår i: Scandinavian Journal of Rheumatology, ISSN 0300-9742, E-ISSN 1502-7732, Vol. 44, nr 2, s. 100-105Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objectives: To compare baseline sociodemographic characteristics in two rheumatoid arthritis (RA) cohorts enrolled 10 years apart, and to examine differences with respect to the general population. Method: Clinical and sociodemographic data were collected in 320 early RA patients during 1996-98 (TIRA-1) and 467 patients in 2006-09 (TIRA-2). Multivariate logistic regression tests were performed and intercohort comparisons were related to general population data, obtained from official databases. Results: TIRA-2 patients were older than TIRA-1 (58 vs. 56 years). Women (both cohorts, 67%) were younger than men in TIRA-1 (55 vs. 59 years) and in TIRA-2 (57 vs. 61 years). Disease activity was similar but TIRA-2 women scored worse pain and worse on the HAQ. Approximately 73% were cohabiting, in both cohorts and in the general population. Education was higher in TIRA-2 than in TIRA-2 but still lower than in the general population. Women had consistently higher education than men. Education was associated with age, younger patients having higher education. In both cohorts, lower education was associated with increased disability pension and increased sick leave. Sick leave was lower in TIRA-2 than in TIRA-1 (37% vs. 50%) but disability pension was higher (16% vs. 10%). In TIRA-1, 9% of women had disability pension compared with 17% in TIRA-2. A similar decrease in sick leave and an increase in disability pension were also seen in the general population. Older age and a higher HAQ score were associated with increased sick leave and being in the TIRA-2 cohort was associated with decreased sick leave. Conclusions: TIRA-2 patients were slightly older, better educated, had lower sick leave and higher disability pension than those in TIRA-1. Similar changes were seen simultaneously in the general population. Belonging to the TIRA-2 cohort was associated with decreased sick leave, indicating that societal changes are of importance.

  • 328.
    Hamilton, Paul J.
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Linköpings universitet, Centrum för social och affektiv neurovetenskap (CSAN).
    Glover, Gary H.
    Stanford University, CA, USA.
    Bagarinao, Epifanio
    Stanford University, CA, USA.
    Chang, Catie
    National Institutes of Health, Bethesda, MD, USA.
    Mackey, Sean
    Stanford University, CA, USA.
    Sacchet, Matthew D.
    Stanford University, CA, USA.
    Gotlib, Ian H.
    Stanford University, CA, USA.
    Effects of salience-network-node neurofeedback training on affective biases in major depressive disorder2016Inngår i: Psychiatry Research: Neuroimaging, ISSN 0925-4927, E-ISSN 1872-7506, Vol. 249, s. 91-96Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Neural models of major depressive disorder (MDD) posit that over-response of components of the brains salience network (SN) to negative stimuli plays a crucial role in the pathophysiology of MDD. In the present proof-of-concept study, we tested this formulation directly by examining the affective consequences of training depressed persons to down-regulate response of SN nodes to negative material. Ten participants in the real neurofeedback group saw, and attempted to learn to down-regulate, activity from an empirically identified node of the SN. Ten other participants engaged in an equivalent procedure with the exception that they saw SN-node neurofeedback indices from participants in the real neurofeedback group. Before and after scanning, all participants completed tasks assessing emotional responses to negative scenes and to negative and positive self-descriptive adjectives. Compared to participants in the sham-neurofeedback group, from pre- to post-training, participants in the realneurofeedback group showed a greater decrease in SN-node response to negative stimuli, a greater decrease in self-reported emotional response to negative scenes, and a greater decrease in self-reported emotional response to negative self-descriptive adjectives. Our findings provide support for a neural formulation in which the SN plays a primary role in contributing to negative cognitive biases in MDD. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

  • 329.
    Hamrin, Elisabeth
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för läkemedelsforskning. Linköpings universitet, Medicinska fakulteten.
    Ernerudh, Jan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk immunologi och transfusionsmedicin.
    Rosén, Anders
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Immunological and Quality-of-Life Profiles in Women with Breast Cancer: Complementary versus Conventional Care2018Inngår i: Complementary Medicine Research, ISSN 2504-2092, Vol. 25, s. 391-397Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Previous studies showed that women with breast cancer treated in anthroposophic clinic versus conventional care had increased quality of life (QoL) parameters, fighting spirit, and anxiety coping. We have now analyzed immune and QoL factors in these 2 groups for possible differences during the first 6 months after admission, prompted by anthroposophic studies, including mistletoe extracts, showing beneficial immune system effects.

    Patients and MethodsFourteen immunological variables, including leukocyte count, lymphocyte count, activated T cells (CD4+ and CD8+), NK cells, B cells, IL1β, IL6, IL10, and oxytocin, were longitudinally analyzed in both groups (n = 2 × 26). A panel of QoL parameters were analyzed using 3 different instruments. Statistical evaluation included that each patient was its own control.

    Results: Cytotoxic CD8+ T cell frequency (percent of lymphocytes analyzed by flow-cytometry) significantly decreased over time in the anthroposophic group versus the conventional group (repeated measures ANOVA, p = 0.05). No major differences were observed in other immunological parameters, whereas QoL variables, anxiety decreased and physical symptoms increased/improved significantly in the anthroposophic group (p = 0.04 and p = 0.05, respectively).

    Conclusion: Overall, women with breast cancer in anthroposophic or conventional therapy did not differ in their immune profiles over time, with exception of decreased cytotoxic T cells in the anthroposophic group. Improvement in physical symptoms along with less anxiety in this group may have influenced the brain-immune axis resulting in lower frequency of CD8+ T cells, a feature associated with less aggressive cancer stages. To evaluate whether this observation is associated with good or bad prognosis, further detailed analyses of memory and naïve CD8+ T cells at tumor site and in blood circulation are essential.

  • 330.
    Hansson, Oskar
    et al.
    Lund Univ, Sweden; Skane Univ Hosp, Sweden.
    Svensson, Martina
    Lund Univ, Sweden.
    Gustaysson, Anna-Marta
    Lund Univ, Sweden; Skane Univ Hosp, Sweden.
    Andersson, Emelie
    Lund Univ, Sweden.
    Yang, Yiyi
    Lund Univ, Sweden.
    Nägga, Katarina
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Närsjukvården i centrala Östergötland, Medicinska och geriatriska akutkliniken. Lund Univ, Sweden.
    Hallmarker, Ulf
    Uppsala Univ, Sweden.
    James, Stefan
    Uppsala Univ, Sweden.
    Deierborg, Tomas
    Lund Univ, Sweden.
    Midlife physical activity is associated with lower incidence of vascular dementia but not Alzheimers disease2019Inngår i: Alzheimer's Research & Therapy, E-ISSN 1758-9193, ALZHEIMERS RESEARCH and THERAPY, Vol. 11, nr 1, artikkel-id 87Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background

    Physical activity might reduce the risk of developing dementia. However, it is still unclear whether the protective effect differs depending on the subtype of dementia. We aimed to investigate if midlife physical activity affects the development of vascular dementia (VaD) and Alzheimer’s disease (AD) differently in two large study populations with different designs.

    Methods

    Using a prospective observational design, we studied whether long-distance skiers of the Swedish Vasaloppet (n = 197,685) exhibited reduced incidence of VaD or AD compared to matched individuals from the general population (n = 197,684) during 21 years of follow-up (median 10, interquartile range (IQR) 5–15 years). Next, we studied the association between self-reported physical activity, stated twice 5 years apart, and incident VaD and AD in 20,639 participants in the Swedish population-based Malmo Diet and Cancer Study during 18 years of follow-up (median 15, IQR 14–17 years). Finally, we used a mouse model of AD and studied brain levels of amyloid-β, synaptic proteins, and cognitive function following 6 months of voluntary wheel running.

    Results

    Vasaloppet skiers (median age 36.0 years [IQR 29.0–46.0], 38% women) had lower incidence of all-cause dementia (adjusted hazard ratio (HR) 0.63, 95% CI 0.52–0.75) and VaD (adjusted HR 0.49, 95% CI 0.33–0.73), but not AD, compared to non-skiers. Further, faster skiers exhibited a reduced incidence of VaD (adjusted HR 0.38, 95% CI 0.16–0.95), but not AD or all-cause dementia compared to slower skiers. In the Malmo Diet and Cancer Study (median age 57.5 years [IQR 51.0–63.8], 60% women), higher physical activity was associated with reduced incidence of VaD (adjusted HR 0.65, 95% CI 0.49-0.87), but not AD nor all-cause dementia. These findings were also independent of APOE-ε4 genotype. In AD mice, voluntary running did not improve memory, amyloid-β, or synaptic proteins.

    Conclusions

    Our results indicate that physical activity in midlife is associated with lower incidence of VaD. Using three different study designs, we found no significant association between physical activity and subsequent development of AD.

  • 331.
    Harada, Fumiya
    et al.
    Health Science University of Hokkaido, Japan; Taipei Medical University, Taiwan.
    Morikawa, Tetsuro
    Health Science University of Hokkaido, Japan.
    Lennikov, Anton
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Far Eastern Federal University, Russia.
    Mukwaya, Anthony
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Schaupper, Mira
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Uehara, Osamu
    Health Science University of Hokkaido, Japan.
    Takai, Rie
    Health Science University of Hokkaido, Japan.
    Yoshida, Koki
    Health Science University of Hokkaido, Japan.
    Sato, Jun
    Health Science University of Hokkaido, Japan.
    Horie, Yukihiro
    Hokkaido University, Japan.
    Sakaguchi, Hiroyuki
    FUJIFILM Corp, Japan.
    Wu, Ching-Zong
    Taipei Medical University Hospital, Taiwan; Lotung Poh Ai Hospital, Taiwan.
    Abiko, Yoshihiro
    Health Science University of Hokkaido, Japan.
    Lagali, Neil
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Ögonkliniken US/LiM.
    Kitaichi, Nobuyoshi
    Hokkaido University, Japan; Health Science University of Hokkaido Hospital, Japan.
    Protective Effects of Oral Astaxanthin Nanopowder against Ultraviolet-Induced Photokeratitis in Mice2017Inngår i: Oxidative Medicine and Cellular Longevity, ISSN 1942-0900, E-ISSN 1942-0994, artikkel-id 1956104Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Purpose. Astaxanthin (AST) has a strong antioxidant cellular membrane chaperone protective effect. Recently, a water-soluble nanosized AST (nano-AST) form was produced, which is expected to improve the efficacy of oral intake effects. The purpose of this study was to examine whether oral nano-AST has therapeutic effects on UV-induced photokeratitis in mice. Methods. C57BL/6 mice were administered twice with either nano-AST, AST oil, lutein, or bilberry extracts 3 hours before and shortly before UV irradiation (dose: 400 mJ/cm2). The corneas were collected 24 hours after irradiation and stained with Hamp;E and TUNEL. NF-kappa B, dihydroethidium (DHE), COX-2, p-I kappa B-alpha, TNF alpha, and CD45 expression were evaluated through immunohistochemistry, Western blot analysis, and qPCR. Results. Corneal epithelium was significantly thicker in mice orally administered with nano-AST than in the others (p amp;lt; 0.01), with significantly less NF-kappa B nucleus translocation (p amp;lt; 0.001), and significantly fewer TUNEL cells (p amp;lt; 0.01). Weaker DHE signals were detected in the nano-AST group (p amp;lt; 0.05) relative to the others. Furthermore, reduced inflammation and decreased cell death in corneal tissue were observed in the nano-AST group, as indicated by a reduction in the expression of COX-2, p-I kappa B-alpha, TNFa, and CD45. Conclusions. Oral administration of nano-AST demonstrated a protective effect on UV-induced photokeratitis via antioxidative, anti-inflammatory, and antiapoptotic activity.

  • 332.
    Harris, Valerie M.
    et al.
    Oklahoma Medical Research Fdn, USA; University of Oklahoma, USA.
    Sharma, Rohan
    University of Oklahoma,USA; Department Vet Affairs Medical Centre, OK USA.
    Cavett, Joshua
    Oklahoma Medical Research Fdn, USA; University of Oklahoma, USA.
    Kurien, Biji T.
    Oklahoma Medical Research Fdn, USA; University of Oklahoma, USA; Department Vet Affairs Medical Centre, OK USA.
    Liu, Ke
    Cincinnati Childrens Hospital Medical Centre, USA; University of Cincinnati, USA.
    Koelsch, Kristi A.
    Oklahoma Medical Research Fdn, USA; University of Oklahoma, USA; Department Vet Affairs Medical Centre, USA.
    Rasmussen, Astrid
    Oklahoma Medical Research Fdn, USA.
    Radfar, Lida
    University of Oklahoma, USA.
    Lewis, David
    University of Oklahoma, USA.
    Stone, Donald U.
    University of Oklahoma, USA; University of Oklahoma, USA.
    Erick Kaufman, C.
    University of Oklahoma, USA.
    Li, Shibo
    University of Oklahoma, USA.
    Segal, Barbara
    University of Minnesota, USA.
    Wallace, Daniel J.
    Cedars Sinai Medical Centre, USA.
    Weisman, Michael H.
    Cedars Sinai Medical Centre, USA.
    Venuturupalli, Swamy
    Cedars Sinai Medical Centre, USA.
    Kelly, Jennifer A.
    Oklahoma Medical Research Fdn, USA.
    Alarcon-Riquelme, Marta E.
    Oklahoma Medical Research Fdn, USA; University of Granada, Spain.
    Pons-Estel, Bernardo
    Sanat Parque, Argentina.
    Jonsson, Roland
    University of Bergen, Norway; Haukeland Hospital, Norway.
    Lu, Xianglan
    University of Oklahoma, USA.
    Gottenberg, Jacques-Eric
    Strasbourg University, France.
    Anaya, Juan-Manuel
    University of Rosario, Colombia.
    Cunninghame-Graham, Deborah S.
    Kings Coll London, England.
    Huang, Andrew J. W.
    University of Minnesota, USA.
    Brennan, Michael T.
    Carolinas Medical Centre, USA.
    Hughes, Pamela
    University of Minnesota, MN USA.
    Alevizos, Ilias
    National Institute Dent and Craniofacial Research, MD USA.
    Miceli-Richard, Corinne
    University of Paris 11, France.
    Keystone, Edward C.
    Mt Sinai Hospital, Canada; University of Toronto, Canada.
    Bykerk, Vivian P.
    Hospital Special Surg, NY USA.
    Hirschfield, Gideon
    University of Birmingham, England.
    Xie, Gang
    University of Toronto, Canada.
    Ng, Wan-Fai
    Newcastle University, England.
    Nordmark, Gunnel
    Uppsala University, Sweden.
    Magnusson Bucher, Sara
    Örebro University Hospital, Sweden.
    Eriksson, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Reumatologiska kliniken i Östergötland.
    Omdal, Roald
    Stavanger University Hospital, Norway.
    Rhodus, Nelson L.
    University of Minnesota, USA.
    Rischmueller, Maureen
    Queen Elizabeth Hospital, Australia; University of Adelaide, Australia.
    Rohrer, Michael
    University of Minnesota, USA.
    Wahren-Herlenius, Marie
    Karolinska Institute, Sweden.
    Witte, Torsten
    Hannover Medical Sch, Germany.
    Mariette, Xavier
    University of Paris 11, France.
    Lessard, Christopher J.
    Oklahoma Medical Research Fdn, USA.
    Harley, John B.
    Cincinnati Childrens Hospital Medical Centre, USA; University of Cincinnati, OH USA; Department Vet Affairs Medical Centre, OH USA.
    Sivils, Kathy L.
    Oklahoma Medical Research Fdn, USA; University of Oklahoma, OK 73190 USA.
    Scofield, R. Hal
    Oklahoma Medical Research Fdn, USA; University of Oklahoma, OK 73190 USA; University of Oklahoma, OK 73190 USA; Department Vet Affairs Medical Centre, OK USA.
    Klinefelters syndrome (47,XXY) is in excess among men with Sjogrens syndrome2016Inngår i: Clinical Immunology, ISSN 1521-6616, E-ISSN 1521-7035, Vol. 168, s. 25-29Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Primary Sjogrens syndrome (pSS) has a strong female bias. We evaluated an X chromosome dose effect by analyzing 47,XXY (Klinefelters syndrome, 1 in 500 live male births) among subjects with pSS. 47,XXY was determined by examination of fluorescence intensity of single nucleotide polymorphisms from the X and Y chromosomes. Among 136 pSS men there were 4 with 47,XXY. This was significantly different from healthy controls (1 of 1254 had 47)0(Y, p = 0.0012 by Fishers exact test) as well men with rheumatoid arthritis (0 of 363 with 47,XXY), but not different compared to men with systemic lupus erythematosus (SLE) (4 of 136 versus 8 of 306, Fishers exact test p = NS). These results are consistent with the hypothesis that the number of X chromosomes is critical for the female bias of pSS, a property that may be shared with SLE but not RA. Published by Elsevier Inc.

  • 333.
    Harris, Valerie M.
    et al.
    Oklahoma Med Res Fdn, OK 73104 USA; Univ Oklahoma, OK 73190 USA.
    Sharma, Rohan
    Univ Oklahoma, OK 73190 USA; US Dept Vet Affairs, OK USA.
    Cavett, Joshua
    Oklahoma Med Res Fdn, OK 73104 USA; Univ Oklahoma, OK 73190 USA.
    Kurien, Biji T.
    Oklahoma Med Res Fdn, OK 73104 USA; Univ Oklahoma, OK 73190 USA; US Dept Vet Affairs, OK USA.
    Liu, Ke
    Cincinnati Childrens Hosp Med Ctr, OH 45229 USA; Univ Cincinnati, OH USA.
    Koelsch, Kristi A.
    Oklahoma Med Res Fdn, OK 73104 USA; Univ Oklahoma, OK 73190 USA; US Dept Vet Affairs, OK USA.
    Rasmussen, Astrid
    Oklahoma Med Res Fdn, OK 73104 USA.
    Radfar, Lida
    Univ Oklahoma, OK 73190 USA.
    Lewis, David
    Univ Oklahoma, OK 73190 USA.
    Stone, Donald U.
    Univ Oklahoma, OK 73190 USA; Univ Oklahoma, OK 73190 USA.
    Kaufman, C. Erick
    Univ Oklahoma, OK 73190 USA.
    Li, Shibo
    Univ Oklahoma, OK 73190 USA; Univ Granada, Spain.
    Segal, Barbara
    Univ Minnesota, MN 55455 USA.
    Wallace, Daniel J.
    Cedars Sinai Med Ctr, CA 90048 USA.
    Weisman, Michael H.
    Cedars Sinai Med Ctr, CA 90048 USA.
    Venuturupalli, Swamy
    Cedars Sinai Med Ctr, CA 90048 USA.
    Kelly, Jennifer A.
    Oklahoma Med Res Fdn, OK 73104 USA.
    Alarcon-Riquelme, Marta E.
    Oklahoma Med Res Fdn, OK 73104 USA.
    Pons-Estel, Bernardo
    Sanatorio Parque, Argentina.
    Jonsson, Roland
    Univ Bergen, Norway; Haukeland Hosp, Norway.
    Lu, Xianglan
    Univ Oklahoma, OK 73190 USA; Univ Granada, Spain.
    Gottenberg, Jacques-Eric
    Strasbourg Univ, France.
    Anaya, Juan-Manuel
    Univ Rosario, Colombia.
    Cunninghame-Graham, Deborah S.
    Kings Coll London, England; Karolinska Inst, Sweden; Kings Coll London, England.
    Huang, Andrew J. W.
    Univ Minnesota, MN USA.
    Brennan, Michael T.
    Carolinas Med Ctr, NC 28232 USA.
    Hughes, Pamela
    Univ Minnesota, MN USA.
    Alevizos, Ilias
    Natl Inst Dent and Craniofacial Res, MD USA.
    Miceli-Richard, Corinne
    Univ Paris Sud, France.
    Keystone, Edward C.
    Mt Sinai Hosp, Canada; Univ Toronto, Canada.
    Bykerk, Vivian P.
    Hosp Special Surg, NY 10021 USA.
    Hirschfield, Gideon
    Univ Birmingham, England.
    Xie, Gang
    Samuel Lunenfeld Res Inst, Canada; Toronto Gen Res Inst, Canada; Univ Toronto, Canada; Univ Toronto, Canada; Univ Toronto, Canada.
    Siminovitch, Katherine A.
    Samuel Lunenfeld Res Inst, Canada; Toronto Gen Res Inst, Canada; Univ Toronto, Canada; Univ Toronto, Canada; Univ Toronto, Canada.
    Ng, Wan-Fai
    Newcastle Univ, England; Newcastle Univ, England.
    Nordmark, Gunnel
    Uppsala Univ, Sweden; Uppsala Univ, Sweden.
    Bucher, Sara Magnusson
    Oklahoma Med Res Fdn, OK 73104 USA; Univ Oklahoma, OK 73190 USA.
    Eriksson, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Reumatologiska kliniken i Östergötland.
    Omdal, Roald
    Stavanger Univ Hosp, Norway.
    Rhodus, Nelson L.
    Univ Minnesota, MN 55455 USA.
    Rischmueller, Maureen
    Queen Elizabeth Hosp, Australia; Univ Adelaide, Australia.
    Rohrer, Michael
    Univ Minnesota, MN USA.
    Wahren-Herlenius, Marie
    Karolinska Inst, Sweden.
    Witte, Torsten
    Hannover Med Sch, Germany.
    Mariette, Xavier
    Univ Paris Sud, France.
    Lessard, Christopher J.
    Oklahoma Med Res Fdn, OK 73104 USA.
    Harley, John B.
    Cincinnati Childrens Hosp Med Ctr, OH 45229 USA; Univ Cincinnati, OH USA; US Dept Vet Affairs, OH USA.
    Sivils, Kathy L.
    Oklahoma Med Res Fdn, OK 73104 USA; Univ Oklahoma, OK 73190 USA.
    Scofield, R. Hal
    Oklahoma Med Res Fdn, OK 73104 USA; Univ Oklahoma, OK 73190 USA; Univ Oklahoma, OK 73190 USA; US Dept Vet Affairs, OK USA.
    Correction: Klinefelters syndrome (47,XXY) is in excess among men with Sjogrens syndrome (vol 168, pg 25, 2016)2018Inngår i: Clinical Immunology, ISSN 1521-6616, E-ISSN 1521-7035, Vol. 187, s. 137-138Artikkel i tidsskrift (Annet vitenskapelig)
    Abstract [en]

    n/a

  • 334.
    Hasib, Lekbira
    et al.
    Linköpings universitet, Medicinska fakulteten. Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin.
    Lundberg, Anna
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten.
    Zachrisson, Helene
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Fysiologiska kliniken US. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV.
    Ernerudh, Jan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk immunologi och transfusionsmedicin.
    Jonasson, Lena
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Kardiologiska kliniken US.
    Functional and homeostatic defects of regulatory T cells in patients with coronary artery disease2016Inngår i: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 279, nr 1, s. 63-77Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    ObjectiveRegulatory T cells (Tregs) are considered atheroprotective, and low levels have been associated with the acute coronary syndrome (ACS), particularly non-ST elevation (NSTE)-ACS. However, the functional properties as well as homeostasis of Tregs are mainly unknown in coronary artery disease (CAD). Here, we investigated the composition and functional properties of naive (n) and memory (m)Tregs in patients with NSTE-ACS and in patients 6-12months post-ACS. MethodsBased on the expression of CD25, FOXP3, CD127, CD45RA, CD39 and CTLA-4, Tregsubsets were defined by flow cytometry in whole blood or isolated CD4(+) T cells. The functional properties of nTregs and mTregs were examined in terms of proliferative capacity and modulation of cytokine secretion. To understand the potential consequences of Treg defects, we also investigated correlations with lipopolysaccharide (LPS)-induced cytokine secretion and ultrasound-defined carotid atherosclerosis. ResultsBoth NSTE-ACS and post-ACS patients exhibited reduced levels of nTregs (P&lt;0.001) compared with healthy control subjects, but without compensatory increases in mTregs. Both nTregs and mTregs from patients showed significantly lower replicative rates and impaired capacity to modulate T-cell proliferation and secretion of interferon-gamma and IL-10. The Treg defect was also associated with LPS-induced cytokine secretion and increased burden of carotid atherosclerosis. ConclusionOur results demonstrate a functional and homeostatic Treg defect in patients with NSTE-ACS and also in stabilized patients 6-12months after ACS. Moreover, this defect was associated with a subclinical proinflammatory and atherogenic state. We believe that the failure to preserve Treg function and homeostasis reflects a need for immune-restoring strategies in CAD.

  • 335.
    Hedberg-Oldfors, Carola
    et al.
    Univ Gothenburg, Sweden.
    Abramsson, Alexandra
    Univ Gothenburg, Sweden.
    Osborn, Daniel P. S.
    St Georges Univ London, England.
    Danielsson, Olof
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Närsjukvården i centrala Östergötland, Neurologiska kliniken.
    Fazlinezhad, Afsoon
    Imam Reza Int Univ, Iran.
    Nilipour, Yalda
    Shahid Beheshti Univ Med Sci, Iran.
    Hübbert, Laila
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Kardiologiska kliniken ViN.
    Nennesmo, Inger
    Karolinska Univ Hosp, Sweden.
    Visuttijai, Kittichate
    Univ Gothenburg, Sweden.
    Bharj, Jaipreet
    St Georges Univ London, England.
    Petropoulou, Evmorfia
    St Georges Univ London, England.
    Shoreim, Azza
    St Georges Univ London, England.
    Vona, Barbara
    Julius Maximilians Univ Wurzburg, Germany.
    Ahangari, Najmeh
    Mashhad Univ Med Sci, Iran.
    Lopez, Marcela Davila
    Univ Gothenburg, Sweden.
    Doosti, Mohammad
    Next Generat Genet Polyclin, Iran.
    Banote, Rakesh Kumar
    Univ Gothenburg, Sweden.
    Maroofian, Reza
    St Georges Univ London, England.
    Edling, Malin
    Univ Gothenburg, Sweden.
    Taherpour, Mehdi
    Imam Reza Int Univ, Iran.
    Zetterberg, Henrik
    Univ Gothenburg, Sweden; Sahlgrens Univ Hosp, Sweden; UCL Inst Neurol, England.
    Karimiani, Ehsan Ghayoor
    Imam Reza Int Univ, Iran; Islamic Azad Univ, Iran.
    Oldfors, Anders
    Univ Gothenburg, Sweden.
    Jamshidi, Yalda
    St Georges Univ London, England.
    Cardiomyopathy with lethal arrhythmias associated with inactivation of KLHL242019Inngår i: Human Molecular Genetics, ISSN 0964-6906, E-ISSN 1460-2083, Vol. 28, nr 11, s. 1919-1929Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiovascular disorder, yet the genetic cause of up to 50% of cases remains unknown. Here, we show that mutations in KLHL24 cause HCM in humans. Using genome-wide linkage analysis and exome sequencing, we identified homozygous mutations in KLHL24 in two consanguineous families with HCM. Of the 11 young affected adults identified, 3 died suddenly and 1 had a cardiac transplant due to heart failure. KLHL24 is a member of the Kelch-like protein family, which acts as substrate-specific adaptors to Cullin E3 ubiquitin ligases. Endomyocardial and skeletal muscle biopsies from affected individuals of both families demonstrated characteristic alterations, including accumulation of desmin intermediate filaments. Knock-down of the zebrafish homologue klhl24a results in heart defects similar to that described for other HCM-linked genes providing additional support for KLHL24 as a HCM-associated gene. Our findings reveal a crucial role for KLHL24 in cardiac development and function.

  • 336.
    Hedenqvist, Clara
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Persson, Frida
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Eklund, Robert
    Linköpings universitet, Institutionen för kultur och kommunikation, Avdelningen för språk och kultur. Linköpings universitet, Filosofiska fakulteten.
    Disfluency incidence in 6-year old Swedish boys and girls with typical language development2015Konferansepaper (Annet vitenskapelig)
    Abstract [en]

    This paper reports the prevalence of disfluencies in agroup of 55 (25F/30M) Swedish children with typical speech development, and within the agerange 6;0 and 6;11. All children had Swedish as their mother tongue. Speech was elicited using an “event picture” which the children described in their own, spontaneously produced, words. The data were analysed with regard to sex differences and lexicalability, including size of vocabulary and wordretrieval, which was assessed using the two tests Peabody Picture Vocabulary Test and Ordracet. Results showed that girls produced significantly more unfilled pauses, prolongations and sound repetitions, while boys produced more word repetitions. However, no correlation with lexical development was found. The results are of interest tospeech pathologists who study early speech development in search for potential early predictorsof speech pathologies.

  • 337.
    Heilig, Markus
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Närsjukvården i centrala Östergötland, Psykiatriska kliniken.
    Alkohol, droger och hjärnan: tro och vetande utifrån modern neurovetenskap2015Bok (Annet vitenskapelig)
    Abstract [sv]

    Alkohol, droger och hjärnan beskriver framsteg inom hjärnforskningen som gjort det möjligt att bättre förstå alkohol- och drogproblem. Boken är skriven från författarens perspektiv som läkare och forskare och visar hur vetenskapens framsteg pekar ut vägar mot empatisk, rationell behandling som alternativ till moraliserande attityder och vårdideologiska strider.

    Missbruksproblem är mycket vanliga, och nästan varje familj har erfarenhet av någon som drabbats. Svenskars användningsmönster av alkohol har förändrats. After Work-ölen och mitt-i-veckan-drinken är förhållandevis nya i svensk dryckeskultur, samtidigt som traditionen av tungt helgdrickande finns kvar. Dessa dryckesbeteenden aktualiserar behovet av fördjupad kunskap och vetenskapligt grundade behandlingsmetoder. För att nå dit behöver forskningens resultat nå ut utanför akademiska kretsar.

  • 338.
    Heilig, Markus
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Linköpings universitet, Centrum för social och affektiv neurovetenskap (CSAN). Region Östergötland, Närsjukvården i centrala Östergötland, Psykiatriska kliniken.
    Substansrelaterade och addiktiva störningar2016Inngår i: Psykiatri / [ed] Jörgen Herlofson, Lund: Studentlitteratur, 2016, 2, s. 493-536Kapittel i bok, del av antologi (Annet vitenskapelig)
    Abstract [en]

    Användning av psykoaktiva substanser (eller "droger") leder till omfattande folkhälsoproblem, men är inte lätt att få in i enkla diagnoskategorier. Det är omdebatterat hurvida substansbruk ska ses som en "sjukdom" och vara en angelägenhet för sjukvården. Vi ska emellertid se att substansbruk ofta uppvisar grundläggande likheter med andra kroniska sjukdomar.

  • 339.
    Heilig, Markus
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Linköpings universitet, Centrum för social och affektiv neurovetenskap (CSAN). Region Östergötland, Närsjukvården i centrala Östergötland, Psykiatriska kliniken.
    Carlezon, William A.
    Harvard University, MA USA.
    Editorial Material: Circumspectives: Cannabis and Psychiatric Illness: Blunt Thoughts in NEUROPSYCHOPHARMACOLOGY, vol 41, issue 2, pp 391-3922016Inngår i: Neuropsychopharmacology, ISSN 0893-133X, E-ISSN 1740-634X, Vol. 41, nr 2, s. 391-392Artikkel i tidsskrift (Annet vitenskapelig)
    Abstract [en]

    n/a

  • 340.
    Heilig, Markus
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Närsjukvården i centrala Östergötland, Psykiatriska kliniken.
    Carlezon, William A. Jr.
    Harvard University, MA USA.
    Editorial Material: Circumspectives: The Replacements in NEUROPSYCHOPHARMACOLOGY, vol 40, issue 8, pp 1813-18142015Inngår i: Neuropsychopharmacology, ISSN 0893-133X, E-ISSN 1740-634X, Vol. 40, nr 8, s. 1813-1814Artikkel i tidsskrift (Annet vitenskapelig)
    Abstract [en]

    n/a

  • 341.
    Heilig, Markus
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Linköpings universitet, Centrum för social och affektiv neurovetenskap (CSAN). Region Östergötland, Närsjukvården i centrala Östergötland, Psykiatriska kliniken.
    Epstein, David H.
    NIDA, MD 21044 USA.
    Nader, Michael A.
    Wake Forest School Med, NC 27157 USA.
    Shaham, Yavin
    NIDA, MD 21044 USA.
    Time to connect: bringing social context into addiction neuroscience2016Inngår i: Nature Reviews Neuroscience, ISSN 1471-003X, E-ISSN 1471-0048, Vol. 17, nr 9, s. 592-599Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    Research on the neural substrates of drug reward, withdrawal and relapse has yet to be translated into significant advances in the treatment of addiction. One potential reason is that this research has not captured a common feature of human addiction: progressive social exclusion and marginalization. We propose that research aimed at understanding the neural mechanisms that link these processes to drug seeking and drug taking would help to make addiction neuroscience research more clinically relevant.

  • 342.
    Hellberg, Sandra
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Effects of Pregnancy and Hormones on T cell Immune Regulation in Multiple Sclerosis2019Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Multiple sclerosis (MS) is characterized by a dysregulated immune system leading to chronic inflammation in the central nervous system. Despite increasing number of treatments, many patients continue to deteriorate. A better understanding of the underlying disease mechanisms involved in driving disease is a pre-requisite for finding new biomarkers and new treatment targets. The improvement of MS during pregnancy, comparable to the beneficial effects of the most effective treatment, suggests that the transient and physiological immune tolerance established during pregnancy could serve as a model for successful immune regulation. Most likely the immune-endocrine alterations that take place during pregnancy to accommodate the presence of the semi-allogenic fetus contribute to the observed disease improvement.

    The aim of this thesis was to characterize the dysregulated immune system in MS and define potential factors and mechanisms established during pregnancy that could be involved in the pregnancy-induced effects in MS, focusing on CD4+ T cells as one of the main drivers in immunity and in the MS pathogenesis. Using a network-based modular approach based on gene expression profiling, we could show that CD4+ T cells from patients with MS displayed an altered dynamic gene response to activation, in line with a dysregulated immune system in MS. The resulting gene module disclosed cell activation and chemotaxis as central components in the deviating response, results that form a basis for further studies on its modulation during pregnancy. Moreover, a combination of secreted proteins (OPN+CXCL1-3+CXCL10-CCL2), identified from the module, could be used to separate patients and controls, predict disease activity after 2 years and discriminate between high and low responders to treatment, highlighting their potential use as biomarkers for predicting disease activity and response to treatment.

    The pregnancy hormone progesterone (P4), a potential factor involved in the pregnancy-induced amelioration of MS, was found to significantly dampen CD4+ T cell activation. Further detailed transcriptomic profiling revealed that P4 almost exclusively down-regulated immune-related pathways in activated T cells, several related to or downstream of T cell activation such as JAKSTAT signaling, T cell receptor signaling and cytokine-cytokine receptor interaction. In particular, P4 significantly affected genes of relevance to diseases known to be modulated during pregnancy, where genes associated to MS were most significantly affected, supporting a role for P4 in the pregnancy-induced immunomodulation. By using another approach, the role of thymus in T cell regulation during pregnancy was assessed. Two established measures of thymic output, CD31 expression and TREC content, were used and showed that thymic output of T cells is maintained during human pregnancy, or even possibly increased in terms of regulatory T cells.

    This thesis further supports a pivotal role for CD4+ T cells and T cell activation in the MS pathogenesis and adds to the knowledge of how they could be involved in driving disease. We identified a novel strategy for capturing central aspects of the deviating response to T cell activation that could be translated into potentially clinically relevant biomarkers. Further, P4 is emerging as a promising candidate for the pregnancy-induced immunomodulation that could be of importance as a future treatment option. Lastly, maintained thymic output of T cells during human pregnancy challenges the rodent-based dogma of an inactive thymus during pregnancy. Thymic dysfunction has been reported not only in MS but also in rheumatoid arthritis, another inflammatory disease that improves during pregnancy, which highlights a potential role for thymus in immune regulation that could be involved in the pregnancy-induced amelioration.

    Delarbeid
    1. Dynamic Response Genes in CD4+T Cells Reveal a Network of Interactive Proteins that Classifies Disease Activity in Multiple Sclerosis
    Åpne denne publikasjonen i ny fane eller vindu >>Dynamic Response Genes in CD4+T Cells Reveal a Network of Interactive Proteins that Classifies Disease Activity in Multiple Sclerosis
    Vise andre…
    2016 (engelsk)Inngår i: Cell reports, ISSN 2211-1247, E-ISSN 2211-1247, Vol. 16, nr 11, s. 2928-2939Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Multiple sclerosis (MS) is a chronic inflammatory disease of the CNS and has a varying disease course as well as variable response to treatment. Biomarkers may therefore aid personalized treatment. We tested whether in vitro activation of MS patient-derived CD4+ T cells could reveal potential biomarkers. The dynamic gene expression response to activation was dysregulated in patient-derived CD4+ T cells. By integrating our findings with genome-wide association studies, we constructed a highly connected MS gene module, disclosing cell activation and chemotaxis as central components. Changes in several module genes were associated with differences in protein levels, which were measurable in cerebrospinal fluid and were used to classify patients from control individuals. In addition, these measurements could predict disease activity after 2 years and distinguish low and high responders to treatment in two additional, independent cohorts. While further validation is needed in larger cohorts prior to clinical implementation, we have uncovered a set of potentially promising biomarkers.

    sted, utgiver, år, opplag, sider
    CELL PRESS, 2016
    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-132056 (URN)10.1016/j.celrep.2016.08.036 (DOI)000383882300014 ()27626663 (PubMedID)
    Merknad

    Funding Agencies|Swedish Research Council [K2013-61X-22310-01-4, K2013-61X-07488-28-5, 2015-03495]; Medical Research Council of Southeast Sweden (FORSS); Swedish Foundation for MS Research; NEURO Sweden; Centre for Industrial IT (CENIIT); Ake Wiberg Foundation; Knut and Alice Wallenberg Foundation; Swedish Brain Foundation; AFA foundation; Margareta af Ugglas foundation; Swedish Society for Medical Research; Biogen; Novartis; Genzyme; Merck; Allmiral; Biogen Idec

    Tilgjengelig fra: 2016-10-18 Laget: 2016-10-17 Sist oppdatert: 2019-10-22
    2. Maintained thymic output of conventional and regulatory T cells during human pregnancy
    Åpne denne publikasjonen i ny fane eller vindu >>Maintained thymic output of conventional and regulatory T cells during human pregnancy
    Vise andre…
    2019 (engelsk)Inngår i: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 143, nr 2, s. 771-775.e7Artikkel i tidsskrift, Letter (Annet vitenskapelig) Published
    Abstract [en]

    n/a

    sted, utgiver, år, opplag, sider
    Philadelphia, United States: Mosby, Inc., 2019
    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-154564 (URN)10.1016/j.jaci.2018.09.023 (DOI)000457718700037 ()30312712 (PubMedID)2-s2.0-85058386317 (Scopus ID)
    Merknad

    Funding Agencies|Swedish Research Council [K2013-61X-22310-01-4]; Medical Research Council of Southeast Sweden [FORSS-315121, FORSS-161101]

    Tilgjengelig fra: 2019-02-20 Laget: 2019-02-20 Sist oppdatert: 2019-10-22bibliografisk kontrollert
  • 343.
    Hellberg, Sandra
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Bhai Mehta, Ratnesh
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Forsberg, Anna
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Berg, Göran
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Barn- och kvinnocentrum, Kvinnokliniken i Linköping.
    Brynhildsen, Jan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Barn- och kvinnocentrum, Kvinnokliniken i Linköping.
    Winqvist, Ola
    Karolinska Inst, Sweden.
    Jenmalm, Maria
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Ernerudh, Jan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk immunologi och transfusionsmedicin.
    Maintained thymic output of conventional and regulatory T cells during human pregnancy2019Inngår i: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 143, nr 2, s. 771-775.e7Artikkel i tidsskrift (Annet vitenskapelig)
    Abstract [en]

    n/a

  • 344.
    Hellberg, Sandra
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Eklund, Daniel
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Gawel, Danuta
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten.
    Köpsén, Mattias
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Medicinska fakulteten. Linköpings universitet, Institutionen för fysik, kemi och biologi, Bioinformatik. Linköpings universitet, Tekniska fakulteten.
    Zhang, Huan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten.
    Nestor, Colm
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten.
    Kockum, Ingrid
    Karolinska Institute, Department Clin Neurosci, Neuroimmunol Unit, S-17177 Linkoping, Sweden.
    Olsson, Tomas
    Karolinska Institute, Department Clin Neurosci, Neuroimmunol Unit, S-17177 Linkoping, Sweden.
    Skogh, Thomas
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Reumatologiska kliniken i Östergötland.
    Kastbom, Alf
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Reumatologiska kliniken i Östergötland.
    Sjöwall, Christopher
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Reumatologiska kliniken i Östergötland.
    Vrethem, Magnus
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Närsjukvården i centrala Östergötland, Neurologiska kliniken.
    Håkansson, Irene
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Benson, Mikael
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Allergicentrum US.
    Jenmalm, Maria
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Gustafsson, Mika
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Bioinformatik. Linköpings universitet, Tekniska fakulteten.
    Ernerudh, Jan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk immunologi och transfusionsmedicin.
    Dynamic Response Genes in CD4+T Cells Reveal a Network of Interactive Proteins that Classifies Disease Activity in Multiple Sclerosis2016Inngår i: Cell reports, ISSN 2211-1247, E-ISSN 2211-1247, Vol. 16, nr 11, s. 2928-2939Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Multiple sclerosis (MS) is a chronic inflammatory disease of the CNS and has a varying disease course as well as variable response to treatment. Biomarkers may therefore aid personalized treatment. We tested whether in vitro activation of MS patient-derived CD4+ T cells could reveal potential biomarkers. The dynamic gene expression response to activation was dysregulated in patient-derived CD4+ T cells. By integrating our findings with genome-wide association studies, we constructed a highly connected MS gene module, disclosing cell activation and chemotaxis as central components. Changes in several module genes were associated with differences in protein levels, which were measurable in cerebrospinal fluid and were used to classify patients from control individuals. In addition, these measurements could predict disease activity after 2 years and distinguish low and high responders to treatment in two additional, independent cohorts. While further validation is needed in larger cohorts prior to clinical implementation, we have uncovered a set of potentially promising biomarkers.

  • 345.
    Hellgren, Kerstin M.
    et al.
    Astrid Lindgren Childrens Hospital, Sweden.
    Törnqvist, Kristina
    University of Lund Hospital, Sweden.
    Jakobsson, Peter
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Ögonkliniken US/LiM.
    Lundgren, Pia
    Umeå University, Sweden.
    Carlsson, Birgitta
    University of Örebro, Sweden.
    Kallen, Karin
    Lund University, Sweden.
    Serenius, Fredrik
    Uppsala University, Sweden.
    Hellstrom, Ann
    University of Gothenburg, Sweden.
    Holmstrom, Gerd
    University of Uppsala Hospital, Sweden.
    Ophthalmologic Outcome of Extremely Preterm Infants at 6.5 Years of Age Extremely Preterm Infants in Sweden Study (EXPRESS)2016Inngår i: JAMA ophthalmology, ISSN 2168-6165, E-ISSN 2168-6173, Vol. 134, nr 5, s. 555-562Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    IMPORTANCE This follow-up study of extremely preterm (EPT) children (&lt;27 weeks gestational age [GA] at birth) revealed major eye and visual problems in 37.9%(147 of 388) of all EPT infants and in 55.4%(67 of 121) of the most immature subgroups at 6.5 years of age. These major eye and visual problems were strongly associated with treatment-requiring retinopathy of prematurity (ROP). OBJECTIVES To investigate the ophthalmologic outcome of a national cohort of EPT children at 6.5 years of age and to evaluate the impact of prematurity and ROP. DESIGN, SETTING, AND PARTICIPANTS All surviving EPT children born in Sweden between April 1, 2004, and March 31, 2007, were included and compared with a matched term control group, as part of a prospective national follow-up study. MAIN OUTCOMES AND MEASURES Visual acuity, refraction in cycloplegia, and manifest strabismus were evaluated and compared with GA at birth and with treatment-requiring ROP. RESULTS The study cohort comprised 486 participants. The mean (SD) GA of the children who were included was 25 (1) weeks, and 45.7%(222 of 486) were female. At a median age of 6.6 years, 89.3%(434 of 486) of eligible EPT children were assessed and compared with 300 control group children. In the EPT group, 2.1%(9 of 434) were blind, 4.8%(21 of 434) were visually impaired according to the World Health Organization criteria, and 8.8% (38 of 434) were visually impaired according to the study criteria. Strabismus was found in 17.4% (68 of 390) and refractive errors in 29.7%(115 of 387) of the EPT children compared with 0% (0 of 299) and 5.9% (17 of 289), respectively, of the control children (P&lt;.001). Altogether at 6.5 years of age, 37.9%(147 of 388) of the EPT children had some ophthalmologic abnormality compared with 6.2%(18 of 290) of the matched control group (95% CI of the difference, 26.1%-37.2%). When treatment-requiring ROP was adjusted for, no significant association between GA and visual impairment could be detected. For refractive errors, the association with GA remained after adjustment for treatment-requiring ROP (odds ratio, 0.72; 95% CI, 0.58-0.91 for each 1-week increment). CONCLUSIONS AND RELEVANCE In a Swedish national cohort of EPT children at 6.5 years of age, major eye and visual problems were frequently found. Treatment-requiring ROP was a stronger impact factor than GA on visual impairment and strabismus, but not on refractive errors, as a whole. In modern neonatal intensive care settings, ophthalmologic problems continue to account for a high proportion of long-term sequelae of prematurity.

  • 346.
    Hellqvist, Carina
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för omvårdnad. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Närsjukvården i centrala Östergötland, Neurologiska kliniken.
    Dizdar Segrell, Nil
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Närsjukvården i centrala Östergötland, Neurologiska kliniken.
    Hagell, Peter
    Kristianstad Univ, Sweden.
    Berterö, Carina
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för omvårdnad. Linköpings universitet, Medicinska fakulteten.
    Sund-Levander, Märtha
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för omvårdnad. Linköpings universitet, Medicinska fakulteten.
    Improving self-management for persons with Parkinsons disease through education focusing on management of daily life: Patients and relatives experience of the Swedish National Parkinson School2018Inngår i: Journal of Clinical Nursing, ISSN 0962-1067, E-ISSN 1365-2702, Vol. 27, nr 19-20, s. 3719-3728Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Aims and objectiveTo identify and describe experiences valuable formanaging daily life after participation in the NPS self-management intervention. The second part was to explore the applicability of the Self- and family management framework by Grey and colleagues for persons with Parkinsons Disease and their relatives. BackgroundThe impact of PD is evident on the lives of both patients and relatives. The National Parkinson School (NPS) is a Swedish self-management programme designed for patients and relatives, aiming at teaching strategies helpful for the ability of self-management, in order to promote life satisfaction. DesignQualitative explorative with inductive and deductive analysis. MethodsFive group discussions with NPS participants were audio-recorded. Verbatim transcriptions were analysed inductively with thematic analysis according to Braun and Clarke, and the findings were then applied deductively to the existing model for patients with chronic disease. ResultsThrough the first step of inductive analysis, three themes capturing the meaning, value and experience of being a participant at the NPS were identified: exchanging experiences and feeling support, adjustment and acceptance of PD for managing daily life and promoting life satisfaction. The deductive analysis applied the inductive findings to the Self- and family management framework of chronically ill to explore the fit to persons with PD and relatives attending the NPS programme. ConclusionsThe NPS programme is a promising approach for helping persons with PD and their relatives to achieve better self-management of disease and improved life satisfaction. Further evaluations of programme outcomes in clinical practice are warranted. Relevance of clinical practiceSelf-management programmes like the NPS is a promising approach in facilitating a positive mindset and outlook on life and gain knowledge to understand, adapt and handle chronic disease, such as PD, better.

  • 347.
    Hellstrom, Amanda
    et al.
    Linnaeus Univ, Sweden.
    Hagell, Peter
    Kristianstad Univ, Sweden.
    Broström, Anders
    Region Östergötland, Sinnescentrum, Neurofysiologiska kliniken US. Jonkoping Univ, Sweden.
    Ulander, Martin
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Neurofysiologiska kliniken US.
    Luik, Annemarie I.
    Univ Oxford, England; Erasmus MC Univ Med Ctr, Netherlands.
    Espie, Colin A.
    Univ Oxford, England.
    Arestedt, Kristofer
    Linnaeus Univ, Sweden; Reg Kalmar Cty, Sweden.
    A classical test theory evaluation of the Sleep Condition Indicator accounting for the ordinal nature of item response data2019Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 14, nr 3, artikkel-id e0213533Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background Insomnia symptoms are common among young adults and affect about 5% to 26% of 19 to 34-year-olds. In addition, insomnia is associated with poor mental health and may affect daily performance. In research, as well as in clinical practice, sleep questionnaires are used to screen for and diagnose insomnia. However, most questionnaires are not developed according to current DSM-5 diagnostic criteria. An exception is the recently developed Sleep Condition Indicator (SCI), an eight-item scale screening for insomnia. Aim The aim of this study was to perform a Classical Test Theory (CTT) based psychometric evaluation of the SCI in a sample of Swedish university students, by taking the ordinal nature of item level data into account. Methods The SCI was translated into Swedish and distributed online to undergraduate students at three Swedish universities, within programs of health, psychology, science or economy. Of 3673 invited students, 634 (mean age 26.9 years; SD = 7.4) completed the questionnaire that, in addition to the SCI, comprised other scales on sleep, stress, lifestyle and students study environment. Data were analyzed according to CTT investigating data completeness, item homogeneity and unidimensionality. Results Polychoric based explorative factor analysis suggested unidimensionality of the SCI, and internal consistency was good (Cronbachs alpha, 0.91; ordinal alpha, 0.94). SCI scores correlated with the Insomnia Severity Index (-0.88) as well as with sleep quality (-0.85) and perceived stress (-0.50), supporting external construct validity. Conclusions These observations support the integrity of the of the SCI. The SCI demonstrates sound CTT-based psychometric properties, supporting its use as an insomnia screening tool.

  • 348.
    Helmfors, Linda
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Molekylär Bioteknik. Linköpings universitet, Tekniska fakulteten.
    Boman, Andrea
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Civitelli, Livia
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Nath, Sangeeta
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Sandin, Linnea
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Janefjord, Camilla
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    McCann, Heather
    Neuroscience Research Australia and University of New South Wales, Australia.
    Zetterberg, Henrik
    Clinical Neurochemistry Laboratory, Department of Neuroscience and Physiology, Sahlgrenska University Hospital, Mölndal, Sweden / UCL Institute of Neurology, Queen Square, London, United Kingdom.
    Blennow, Kaj
    Clinical Neurochemistry Laboratory, Department of Neuroscience and Physiology, Sahlgrenska University Hospital, Mölndal, Sweden.
    Halliday, Glenda
    UCL Institute of Neurology, Queen Square, London, United Kingdom.
    Brorsson, Ann-Christin
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Molekylär Bioteknik. Linköpings universitet, Tekniska fakulteten.
    Kågedal, Katarina
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Protective properties of lysozyme on β-amyloid pathology: implications for Alzheimer disease2015Inngår i: Neurobiology of Disease, ISSN 0969-9961, E-ISSN 1095-953X, Vol. 83, s. 122-133Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The hallmarks of Alzheimer disease are amyloid-β plaques and neurofibrillary tangles accompanied by signs of neuroinflammation. Lysozyme is a major player in the innate immune system and has recently been shown to prevent the aggregation of amyloid-β1-40 in vitro. In this study we found that patients with Alzheimer disease have increased lysozyme levels in the cerebrospinal fluid and lysozyme co-localized with amyloid-β in plaques. In Drosophila neuronal co-expression of lysozyme and amyloid-β1-42 reduced the formation of soluble and insoluble amyloid-β species, prolonged survival and improved the activity of amyloid-β1-42 transgenic flies. This suggests that lysozyme levels rise in Alzheimer disease as a compensatory response to amyloid-β increases and aggregation. In support of this, in vitro aggregation assays revealed that lysozyme associates with amyloid-β1-42 and alters its aggregation pathway to counteract the formation of toxic amyloid-β species. Overall, these studies establish a protective role for lysozyme against amyloid-β associated toxicities and identify increased lysozyme in patients with Alzheimer disease. Therefore, lysozyme has potential as a new biomarker as well as a therapeutic target for Alzheimer disease.

  • 349.
    Helmfrid, Ingela
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Arbets- och miljömedicin.
    Exposure and body burden of environmental pollution and risk of cancer in a historically contaminated areas2019Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    There are many villages where environmental contamination is substantial due to historical industrial activities. According to the European Environment Agency, there are about 2.5 million potentially contaminated sites in the European member states. In Sweden, there are about 80 000 more or less contaminated areas. About 1000 of them are classified into the highest risk category, Hazard Class 1, and should be remediated. Population exposure due to these industrially contaminated sites may contribute to adverse health effects and is a global environmental problem.

    The general aim of this thesis was to evaluate the occurrence of cancer in populations residing in contaminated areas in relation to indirect exposure via the long-term consumption of locally produced food, taking into account residential, occupational and lifestyle factors. Associations between reported local food consumption frequencies, biomarker concentrations and environmental and lifestyle factors were explored. The Swedish national cancer registers and questionnaire information was used to identify cancer risk groups in the study population. The questionnaire was evaluated regarding how well it reflected measured levels of biomarkers in human biological samples, and how the consumption of local food from contaminated areas contributed to the total body burden of contaminants.

    Despite historically high environmental levels of contaminants in the soil and sediments, current contaminant exposure in the studied population living in the contaminated areas was similar to or only moderately higher than that of the general population.

    No significant associations with increased cancer risk were detected in the highest tertile of metals concentrations in blood or PAH in urine.

    Reported long-term high consumption of certain local foods was associated with higher cadmium (vegetarian food) and lead (fish, meat) concentrations in blood and urine. Long-term high consumption of non-local food from places outside the study areas was not associated with increased concentrations of metals compared with consumers of local food. It was concluded that the questionnaire information on consumption of locally produced food describes differences in food consumption in the study population reasonably well.

    An increased risk of cancer was associated with smoking, family history of cancer and obesity. Residing in a contaminated area during the first five years of life was associated with an increased risk of cancer, which may indicate exposure to contaminants in early life. Also, long-term high consumption of particular local foods (fish, chicken, lamb, game meat) was associated with an increased risk of various forms of cancer, while reported high consumption of these foods from non-local sources was not associated with increased risk of cancer. The associations between habitual consumption of local food and different types of cancer may reflect a higher exposure in the past, and thus, if consumption of local food contributes to the risk of acquiring cancer, that contribution is probably lower today than previously. Furthermore, it cannot be ruled out that other contaminants in the food contribute to the increased cancer risks observed.

    In conclusion, the questionnaire that was developed for the present thesis can identify risk groups within populations and can be used as a tool in a health-risk assessment.

    Delarbeid
    1. Health effects and exposure to polychlorinated biphenyls (PCBs) and metals in a contaminated community
    Åpne denne publikasjonen i ny fane eller vindu >>Health effects and exposure to polychlorinated biphenyls (PCBs) and metals in a contaminated community
    2012 (engelsk)Inngår i: Environment International, ISSN 0160-4120, E-ISSN 1873-6750, Vol. 44, s. 53-58Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Environmental measurements carried out by local authorities during the 1970s, 80s and 90s in an area contaminated by hundreds of years of industrial activities have revealed high levels of zinc (Zn), copper (Cu), lead (Pb) and cadmium (Cd) in soil, vegetables, root crops, berries and mushrooms. In 1972, a large quantity of oil contaminated with polychlorinated biphenyls (PCBs) was accidentally spilled into the river running through the village. To investigate the possible health effects of exposure from local sources, all cancer diagnoses, registered in 1960-2003 for individuals living in the study area, were collected from the regional cancer register of southeast Sweden. The total cancer incidence was non-significantly decreased both among males and females as compared to national rates (SIR = 0.91) for each gender. Among males, increased risks, of border-line significance, were seen for testicular cancer and lymphomas as well as significantly decreased risks for cancer in the rectum, respiratory system and brain. Information on lifetime residence, occupation, smoking habits, diseases, childbirth and food consumption, was collected via questionnaires from cancer cases and randomly selected controls. In both genders combined, significant associations were found for total cancer and high consumption of local perch, and for lymphomas and high consumption of both perch and pikeperch. Female breast cancer was significantly associated with high consumption of local perch and pike as well as with work in metal production. Mothers residing in the parish before the age of five reported significantly more preterm child deliveries. In spite of study limitations, the results indicate that residing in a rural contaminated area may contribute to the development of certain cancers and reproductive effects. In females, high consumption of local fish was shown to be the strongest determinant for total cancer, while in males, the strongest determinant was residing in the study area the first five years of life. Further research including validation of exposure using biomarkers is required to verify the findings as well as future studies in other polluted areas in Sweden with larger population bases.

    sted, utgiver, år, opplag, sider
    Elsevier, 2012
    Emneord
    Contaminated area, Polychlorinated biphenyls, Heavy metals, Cancer, Reproduction
    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-79086 (URN)10.1016/j.envint.2012.01.009 (DOI)000304745900007 ()
    Merknad

    Funding Agencies|Cancer and Allergy Fund, Sweden||

    Tilgjengelig fra: 2012-06-29 Laget: 2012-06-29 Sist oppdatert: 2019-10-31
    2. Exposure and body burden of polychlorinated biphenyls (PCB) and metals in a historically contaminated community.
    Åpne denne publikasjonen i ny fane eller vindu >>Exposure and body burden of polychlorinated biphenyls (PCB) and metals in a historically contaminated community.
    Vise andre…
    2015 (engelsk)Inngår i: Environment International, ISSN 0160-4120, E-ISSN 1873-6750, Vol. 76, s. 41-8Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    There are many small villages where environmental contamination is substantial due to historical industrial activities. The aim of the present study was to investigate if long-term or current consumption of local foods, as reported in food frequency questionnaires, co-vary with measured concentrations of polychlorinated biphenyls (PCBs), organochlorine pesticides (OCPs), lead (Pb), cadmium (Cd) and mercury (Hg) in blood, urine and hair from a population living in a historically contaminated village. Blood, urine and hair were provided by men (n=38) and women (n=57), who had participated in a previous case-control study in the contaminated area, and were analyzed for PCB, OCPs, Pb, Cd and Hg. A detailed food frequency questionnaire, used in the previous epidemiological study, was repeated, and up-dated information of life-style, exposure factors and other covariates was collected. Associations between reported consumption of local foods and exposure biomarkers were explored in relation to age, gender, life-style factors and other covariates. A large part of the population in the area reported consumption of local food, and thus, was potentially exposed to the contaminants. Despite the limited number of participants and other weaknesses described, it was possible to link reported consumption of different foods to biomarker concentrations. Reported consumption of local vegetables, forest berries and mushrooms co-varied with urinary Cd, indicating an influence from the contaminated area on the Cd exposure. We found no associations between PCB plasma concentrations with reported consumption of local fish, but with consumption of herring (non-local sea fish) which is typically high in PCB. Pesticide (HCB, p,p'-DDE, trans-nonachlor) exposure was mainly associated with agricultural work and having a private well the first five years of life, but we found no associations between pesticide concentrations in plasma and consumption of local vegetables or fish. Exposure to Hg was associated with consumption of fish, both local and non-local, and Pb exposure was associated with the consumption of game. Overall, the contaminant concentrations measured in blood, urine and hair varied substantially among study participants, but on average, the concentrations were similar to concentrations measured in other groups of the general Swedish population in the same age range. Larger studies are needed to evaluate health risks (and causality) associated with historical environmental contamination.

    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-113646 (URN)10.1016/j.envint.2014.12.004 (DOI)000349585600004 ()25529270 (PubMedID)
    Merknad

    We express our gratitude to the participating population. We thank the research nurse Louice Eskilsson for an excellent assistance in sample collection and for the dispatch of questionnaires together with Anna-Lena Hallsten. The study was partially financed by the Swedish Environmental Protection Agency, grant no. 502-4531-09.

    Tilgjengelig fra: 2015-01-27 Laget: 2015-01-27 Sist oppdatert: 2019-10-16
    3. Exposure of metals and PAH through local foods and risk of cancer in a historically contaminated glasswork area
    Åpne denne publikasjonen i ny fane eller vindu >>Exposure of metals and PAH through local foods and risk of cancer in a historically contaminated glasswork area
    Vise andre…
    2019 (engelsk)Inngår i: Environment International, ISSN 0160-4120, E-ISSN 1873-6750, Vol. 131, artikkel-id UNSP 104985Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Background

    Production of crystal glass and colored art glassware have been going on in the south-eastern part of Sweden since the 1700s, at over 100 glassworks and smaller glass blowing facilities, resulting in environmental contamination with mainly arsenic (As), cadmium (Cd), lead (Pb) and polycyclic hydrocarbons (PAH). High levels of metals have been found in soil, and moderately elevated levels in vegetables, mushrooms and berries collected around the glassworks sites compared with reference areas. Food in general, is the major exposure source to metals, such as Cd and Pb, and PAHs. Exposure to these toxic metals and PAH has been associated with a variety of adverse health effects in humans including cancer.

    Objective

    The aim of the present study was to evaluate the occurrence of cancer in a cohort from the contaminated glasswork area in relation to long-term dietary intake of locally produced foods, while taking into account residential, occupational and life styles factors.

    Methods

    The study population was extracted from a population cohort of 34,266 individuals who, at some time between the years 1979–2004, lived within a 2 km radius of a glassworks or glass landfill. Register information on cancer incidence and questionnaire information on consumption of local foods (reflecting 30 years general eating habits), life-time residence in the area, life style factors and occupational exposure was collected. Furthermore, blood (n = 660) and urine (n = 400) samples were collected in a subsample of the population to explore associations between local food consumption frequencies, biomarker concentrations in blood (Cd, Pb, As) and urine (PAH metabolite 1-OHPy) as well as environmental and lifestyle factors. The concurrent exposure to persistent organic pollutants (POPs) from food was also considered. A case-control study was performed for evaluation of associations between intakes of local food and risk of cancer.

    Results

    Despite high environmental levels of Cd, Pb and As at glasswork sites and landfills, current metal exposure in the population living in the surrounding areas was similar or only moderately higher in our study population compared to the general population. Reported high consumption of certain local foods was associated with higher Cd and Pb, but not As, concentrations in blood, and 1-OHPy in urine. An increased risk of cancer was associated with smoking, family history of cancer, obesity, and residence in glasswork area before age 5 years. Also, a long-term high consumption of local foods (reflecting 30 years general eating habits), i.e. fish and meat (game, chicken, lamb), was associated with increased risk of various cancer forms.

    Conclusions

    The associations between consumption of local food and different types of cancer may reflect a higher contaminant exposure in the past, and thus, if consumption of local food contributes to the risk of acquiring cancer, that contribution is probably lower today than before. Furthermore, it cannot be ruled out that other contaminants in the food contribute to the increased cancer risks observed.

    sted, utgiver, år, opplag, sider
    Elsevier, 2019
    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-160953 (URN)10.1016/j.envint.2019.104985 (DOI)000493550200042 ()31319292 (PubMedID)2-s2.0-85068874468 (Scopus ID)
    Merknad

    Funding agencies: Swedish Environmental Protection Agency; Medical Research Council of Southeast Sweden; Kamprad Family Foundation, Sweden; Occupational and Environmental Medicine, Linkoping University Hospital, Sweden

    Tilgjengelig fra: 2019-10-16 Laget: 2019-10-16 Sist oppdatert: 2019-12-04bibliografisk kontrollert
  • 350.
    Helmfrid, Ingela
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Arbets- och miljömedicin.
    Ljunggren, Stefan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Arbets- och miljömedicin.
    Nosratabadi, Ali Reza
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Augustsson, Anna
    Linnaeus University, Kalmar, Sweden.
    Filipsson, Monika
    Linnaeus University, Kalmar, Sweden.
    Fredrikson, Mats
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Karlsson, Helen
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Arbets- och miljömedicin.
    Berglund, Marika
    Karolinska Institutet, Stockholm, Sweden.
    Exposure of metals and PAH through local foods and risk of cancer in a historically contaminated glasswork area2019Inngår i: Environment International, ISSN 0160-4120, E-ISSN 1873-6750, Vol. 131, artikkel-id UNSP 104985Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background

    Production of crystal glass and colored art glassware have been going on in the south-eastern part of Sweden since the 1700s, at over 100 glassworks and smaller glass blowing facilities, resulting in environmental contamination with mainly arsenic (As), cadmium (Cd), lead (Pb) and polycyclic hydrocarbons (PAH). High levels of metals have been found in soil, and moderately elevated levels in vegetables, mushrooms and berries collected around the glassworks sites compared with reference areas. Food in general, is the major exposure source to metals, such as Cd and Pb, and PAHs. Exposure to these toxic metals and PAH has been associated with a variety of adverse health effects in humans including cancer.

    Objective

    The aim of the present study was to evaluate the occurrence of cancer in a cohort from the contaminated glasswork area in relation to long-term dietary intake of locally produced foods, while taking into account residential, occupational and life styles factors.

    Methods

    The study population was extracted from a population cohort of 34,266 individuals who, at some time between the years 1979–2004, lived within a 2 km radius of a glassworks or glass landfill. Register information on cancer incidence and questionnaire information on consumption of local foods (reflecting 30 years general eating habits), life-time residence in the area, life style factors and occupational exposure was collected. Furthermore, blood (n = 660) and urine (n = 400) samples were collected in a subsample of the population to explore associations between local food consumption frequencies, biomarker concentrations in blood (Cd, Pb, As) and urine (PAH metabolite 1-OHPy) as well as environmental and lifestyle factors. The concurrent exposure to persistent organic pollutants (POPs) from food was also considered. A case-control study was performed for evaluation of associations between intakes of local food and risk of cancer.

    Results

    Despite high environmental levels of Cd, Pb and As at glasswork sites and landfills, current metal exposure in the population living in the surrounding areas was similar or only moderately higher in our study population compared to the general population. Reported high consumption of certain local foods was associated with higher Cd and Pb, but not As, concentrations in blood, and 1-OHPy in urine. An increased risk of cancer was associated with smoking, family history of cancer, obesity, and residence in glasswork area before age 5 years. Also, a long-term high consumption of local foods (reflecting 30 years general eating habits), i.e. fish and meat (game, chicken, lamb), was associated with increased risk of various cancer forms.

    Conclusions

    The associations between consumption of local food and different types of cancer may reflect a higher contaminant exposure in the past, and thus, if consumption of local food contributes to the risk of acquiring cancer, that contribution is probably lower today than before. Furthermore, it cannot be ruled out that other contaminants in the food contribute to the increased cancer risks observed.

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