| 1. |
- Esberg, Anders, et al.
(författare)
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43-Year Temporal Trends in Immune Response to Oral Bacteria in a Swedish Population
- 2020
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Ingår i: Pathogens. - Basel : MDPI. - 2076-0817. ; 9:7
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Tidskriftsartikel (refereegranskat)abstract
- Bacteria colonizing the mouth induce an adaptive immune response with the systemic and local presence of species or strain-specific immunoglobulins. Few studies have addressed global antibody patterns for oral bacteria or potential population time trends. We assessed these aspects in relation to a panel of oral bacteria. Using multiplex immunoblotting, IgG levels for 26 oral bacterial species (54 strains) were determined in 888 plasma samples from 30-year-old early pregnant women (n = 516) and 50-year-old men and women (n = 372) collected between 1976 and 2018. Inter-species correlations were found and age-dependent profiles and levels of immune responses to oral bacteria confirmed. We found temporal trends in the global and single-species antibody responses, but this was age-specific with both inclining and declining shifts. Prominent shifts in the younger group increased IgG towards health-associated Streptococcus salivarius and Streptococcus sanguinis, and in the older group towards disease-associated Aggregatibacter actinomycetemcomitans, Filifactor alocis, and Streptococcus mutans, among others. We concluded that temporal shifts occurred from 1976 to 2018, which may reflect improved oral health (more remaining teeth) and altered lifestyle habits, but this needs to be evaluated in observational studies considering more aspects.
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| 2. |
- Gomez-Bañuelos, Eduardo, et al.
(författare)
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Exposure to Aggregatibacter Actinomycetemcomitans before Symptom Onset and the Risk of Evolving to Rheumatoid Arthritis
- 2020
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Ingår i: Journal of Clinical Medicine. - Basel : MDPI. - 2077-0383. ; 9:6
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Tidskriftsartikel (refereegranskat)abstract
- Periodontal disease has been implicated in the pathogenesis of rheumatoid arthritis (RA), an autoimmune disease characterized by immune-mediated synovial damage, and antibodies to citrullinated antigens. Here, we investigate the association between exposure to the periodontal pathogen Aggregatibacter actinomycetemcomitans (Aa) and the development of RA. IgM, IgG and IgA antibodies to Aa leukotoxin A (LtxA) were detected by ELISA in plasma from a cohort of Swedish adults at different stages of RA development, from before onset of symptoms to established disease. Patients with early and established RA had increased levels of anti-LtxA IgM compared with matched non-RA controls and periodontally healthy individuals. Logistic regression revealed that anti-LtxA IgM levels were associated with RA during early disease (OR 1.012, 95%CI 1.007, 1.017), which was maintained after adjustment for smoking, anti-CCP antibodies, rheumatoid factor, HLA-DRB1 shared epitope alleles and sex. We found no association between anti-LtxA IgG/IgA antibodies and RA at any stage of disease development. The data support a temporal association between anti-LtxA IgM antibodies and the development of RA, suggesting that a subset of RA patients may have been exposed to Aa around the time of transition from being asymptomatic to become a patient with RA.
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| 3. |
- Berglin, Ewa, MD, PhD, 1955-, et al.
(författare)
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Protein profiling in individuals before onset of anca-associated vasculitis
- 2020
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ Publishing Group Ltd. - 0003-4967 .- 1468-2060. ; 79, s. 372-372
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Etiology and pathogenesis of ANCA-associated vasculitis (AAV) is multifactorial and understanding of the processes leading from a healthy immune system to autoimmunity and on to debut of symptoms in AAV is rudimentary.Objectives:To identify inflammatory proteins related to the early processes preceding AAV development, and potential novel biomarkers, using large-scale protein analysesMethods:The Swedish National Patient Register of in-patient carevand the Swedish Cause of Death Register with discharge diagnosis from ICD-9 and-10 for AAV were co-analysed with the registers of 4 different blood biobanks to identify AAV individuals with available samples predating onset of symptom. Of the pre-AAV cases 86 (36 male, 50 female; mean age (SD); 51.9 (16.9) years) were identified with at least one plasma or serum sample (28 plasma, and 100 serum) pre-dating symptom onset (mean (SD); -4.3 (3.1) years), and 14 had 2-3 samples. Serum and plasma control samples matched for sex, age and sampling date were identified (n=198; 82 male, 116 female; mean age (SD); 51.9±15.9 years). The samples were analysed for levels of 92 proteins using proximity extension assay (OLINK inflammation panel, SciLifeLab, Uppsala, Sweden). Data were analysed using routine statistical methods, random forest and Partial Least square-discriminant analysis (PLS-DA).Results:As previously described for the assay significant difference between plasma and serum samples were observed both in pre-AAV individuals and controls. In pre-AAV plasma samples significantly increased concentrations of interleukin (IL)-2, chemokine ligand (CCL)-4, fibroblast growth factor (FGF)21, IL-4 and CCL20 were found closer to symptom onset, (<5 years) than later (> 5 years) and compared with controls. In serum tumor necrosis factor receptor superfamily member (TNFRSF)9, CXCL9, osteoprotegerin and vascular endothelial growth factor-A were significantly increased <5 years before onset vs. later (>5 years) and compared with controls. PLS-DA score scattered plot separated the pre-AAV individuals from healthy controls (R2=0.26), with significantly increased levels of CCL23, CXCL5, and matrix metalloproteinases-1 (MMP-1),transforming growth factor-ß, orosomucoid, en-rage (S100A12) and IL-7 and decreased FGF-19 level in serum. Binary logistic regression analyses comparing tertiles for these proteins confirmed significantly increased odds ratios for disease development of CCL23, CXCL5 and MMP-1. The findings were confirmed in random forest analysis where these factors were among the 20 most discriminatory factors between pre-symptomatic AAV and controls.Conclusion:In serum samples collected years before symptom onset of AAV, proteins involved in immune system activation were increased, suggesting that the inflammatory process is initiated long before clinical manifestations of the disease appear. These findings propose the elevated proteins as novel biomarkers for disease progression.References:[1]Watts et al. Ann Rheum Dis 2007;66:222-22Acknowledgments:Vasculitis Foundation, USADisclosure of Interests:Ewa Berglin: None declared, Anders Esberg: None declared, Johanna Dahlqvist: None declared, Johanna Sjöwall: None declared, Anders Lundquist: None declared, Kristina Lejon: None declared, Ingegerd Johansson: None declared, Aladdin J Mohammad Speakers bureau: lecture fees from Roche and Elli Lilly Sweden, PI (GiACTA study), Solbritt Rantapää Dahlqvist: None declared
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| 4. |
- Buhlin, Kare, et al.
(författare)
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Association of periodontitis with persistent, pro-atherogenic antibody responses
- 2015
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Ingår i: Journal of Clinical Periodontology. - : Wiley-Blackwell. - 0303-6979 .- 1600-051X. ; 42:11, s. 1006-1014
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Tidskriftsartikel (refereegranskat)abstract
- AIM: To study antibody responses associated with molecular mimicry in periodontitis.MATERIAL AND METHODS: Fifty-four periodontitis cases (mean age 54.0 years) and 44 controls (53.6 years) were examined, after which cases received periodontal treatment. Established immunoassays were used to analyse levels of antibodies against two pathogens, Aggregatibacter actinomycetemcomitans (Aa) and Porphyromonas gingivalis (Pg), heat shock proteins (Hsp), Hsp60, Hsp65, and Hsp70, and epitopes of oxidized low density lipoprotein (oxLDL) (CuOx-LDL and MDA-LDL) in plasma samples that were collected at baseline, after 3 (n=48) and 6 (n=30) months.RESULTS: When age, sex, smoking habit, and the number of teeth were considered in multivariate logistic regressions, Aa and Pg IgG, Hsp65-IgA, CuOx-LDL-IgG and -IgM and MDA-LDL-IgG antibody levels were associated with periodontitis, whereas Hsp60-IgG2 antibody levels were inversely associated. The Aa antibody levels significantly correlated with the levels of IgA antibodies to Hsp65 and Hsp70, and both OxLDL IgA-antibody levels. The levels of antibodies to Pg correlated with IgG antibodies to Hsp60, Hsp70 and both oxLDL antibody epitopes. None of the antibody levels changed significantly after treatment.CONCLUSIONS: Periodontitis is associated with persistently high levels of circulating antibodies that are reactive with pathogen- and host-derived antigens.
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| 5. |
- Claesson, Rolf, et al.
(författare)
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Multilocus Sequence Typing of Non-JP2 Serotype b Aggregatibacter actinomycetemcomitans Strains of Ghanaian and Swedish Origin
- 2021
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Ingår i: Frontiers in Cellular and Infection Microbiology. - : Frontiers Media S.A.. - 2235-2988. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Objective and Methods: The Gram-negative bacterium, Aggregatibacter actinomycetemcomitans is associated with periodontitis affecting young individuals. The geographic dissemination of the highly leukotoxic JP2 genotype of serotype b of this species was previously studied by multilocus sequence typing (MLST). Here, we have used MLST to genetically characterize non-JP2 genotype strains of serotype b, isolated from individuals living in Ghana (n=41), and in Sweden (n=13), respectively.Results: The MLST analysis revealed a total of nine sequence types (ST). Both Ghanaian and Swedish isolates were distributed in ST 1-3. ST 5 and 6 were only identified among the Ghanaian strains, whereas ST 4, 7, 8 and 9 were uniquely represented among the Swedish strains. Previously, we characterized these non-JP2 genotype strains of A. actinomycetemcomitans serotype b by arbitrarily-primed (AP)-PCR, which distributed them into three groups, AP-PCR type 1, 2, and 3, respectively. AP-PCR type 1 strains are generally highly leukotoxic, and are associated with progression of periodontal attachment loss. As AP-PCR type 1 includes both JP2 genotype strains and a proportion of non-JP2 genotype strains of serotype b, a straightforward diagnostic procedure has been sought. This has revealed a gene, cagE, which appears to be conserved only in this AP-PCR type. According to our results, MLST was not a highly discriminatory method to identify AP-PCR type 1, as strains of this AP-PCR type could be found within three different ST: ST 2, ST 3 and ST 8.Conclusion: According to MLST, a geographic dissemination of non-JP2 genotype A. actinomycetemcomitans serotype b appears to exist. However, aiming to identify carriers of AP-PCR type 1, non-JP2 genotype serotype b, PCR with cagE-specific primers is likely the most efficient diagnostic procedure known today.
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| 6. |
- Ekman, Inger, 1952, et al.
(författare)
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Person-centered care -ready for prime time.
- 2011
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Ingår i: European Journal of Cardiovascular Nursing. - : Sage Publications. - 1474-5151 .- 1873-1953. ; 10:4, s. 248-251
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Tidskriftsartikel (refereegranskat)abstract
- Long-term diseases are today the leading cause of mortality worldwide and are estimated to be the leading cause of disability by 2020. Person-centered care (PCC) has been shown to advance concordance between care provider and patient on treatment plans, improve health outcomes and increase patient satisfaction. Yet, despite these and other documented benefits, there are a variety of significant challenges to putting PCC into clinical practice. Although care providers today broadly acknowledge PCC to be an important part of care, in our experience we must establish routines that initiate, integrate, and safeguard PCC in daily clinical practice to ensure that PCC is systematically and consistently practiced, i.e. not just when we feel we have time for it. In this paper, we propose a few simple routines to facilitate and safeguard the transition to PCC. We believe that if conscientiously and systematically applied, they will help to make PCC the focus and mainstay of care in long-term illness.
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| 7. |
- Eliasson, Alf, 1959, et al.
(författare)
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The precision of fit of milled titanium implant frameworks (I-Bridge) in the edentulous jaw.
- 2010
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Ingår i: Clinical implant dentistry and related research. - : Wiley. - 1708-8208 .- 1523-0899. ; 12:2, s. 81-90
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: New computer numeric controlled (CNC)-milled frameworks for implant-supported prostheses have been introduced. However, no data are available on the precision of fit of these new frameworks. PURPOSE: The purpose of this study is to evaluate the precision of fit of a new CNC-milled framework technique (I-Bridge, Biomain AB, Helsingborg, Sweden) using Brånemark System (Nobel Biocare AB, Göteborg, Sweden) and NobelReplace (Nobel Biocare AB) system implants. MATERIALS AND METHODS: Ten test frameworks were fabricated for one master model for each implant system. Five additional frameworks were fabricated for five different models simulating clinical cases as controls (Brånemark System). The distortion of implant center point positions was measured in x-, y-, and z-axes and in three dimensions by using a contact-type coordinate measuring machine and a computer program developed specifically for this purpose. Mann-Whitney U-test was used to compare differences of distortion within and between the groups. RESULTS: The maximal distortion in arch width (x-axis) and curvature (y-axis) was within 71 and 55 microm for all frameworks, respectively. The mean distortion in absolute figures in x-, y-, z-axes and three dimensions was for "clinical control" frameworks 23, 26, 4, and 34 microm as compared with less than 12, 12, 2, and 17 microm for Brånemark and NobelReplace frameworks, respectively. Control frameworks showed significantly (p < .05) greater mean and range of distortions in x- and y-axes and in three dimensions compared with test frameworks. CONCLUSION: All measured frameworks presented signs of misfit, indicating that no framework had a "passive fit." Frameworks produced in a more routine clinical environment seem to present greater levels of distortion as compared with frameworks produced in a strict test situation. However, all measured frameworks presented levels of precision of fit within limits considered to be clinically acceptable in earlier studies of frameworks placed on abutments.
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| 8. |
- Ellingsen, Jan Eirik, et al.
(författare)
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Improved retention and bone-tolmplant contact with fluoride-modified titanium implants.
- 2004
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Ingår i: International Journal of Oral & Maxillofacial Implants. - 0882-2786. ; 19:5, s. 659-66
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: The purpose of the present study was to investigate whether a fluoride modification of the titanium surface would have an effect on bone response after implantation. MATERIALS AND METHODS: Titanium-oxide-blasted titanium implants with and without fluoride modification were investigated in a rabbit tibia model. Quantitative analysis of surface roughness, biomechanical interlocking, and in vivo tissue reactions in rabbit bone at 1 and 3 months after placement were compared. RESULTS: The fluoride-modified test implants had a slightly smoother surface (Sa: 0.91 +/- 0.14 microm) than the unmodified control implants (Sa: 1.12 +/- 0.24 microm). Significantly higher removal torque values (85 +/- 16 Ncm vs 54 +/- 12 Ncm) and shear strength between bone and implants (23 +/- 9 N/mm2 vs 15 +/- 5 N/mm2) were measured for the fluoride-modified implants after 3 months. The histomorphometric evaluations demonstrated higher bone-to-implant contact for test implants at 1 month (35% +/- 14% vs 26% +/- 8%) and 3 months (39% +/- 11% vs 31% +/- 6%) after placement. DISCUSSION: Implant surface modification with fluoride may result in morphologic and physiochemical phenomena that are of significance for the bone response. Another possible explanation for the findings in the present study is that a surface modification changes the surface chemical structures to be more suitable for bone bonding. CONCLUSION: Based on the biomechanical and histomorphometric data, the fluoride-modified titanium implants demonstrated a firmer bone anchorage than the unmodified titanium implants. These implants achieved greater bone integration than unmodified titanium implants after a shorter healing time.
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| 9. |
- Engstrand, Per O., 1955-, et al.
(författare)
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Mekmassainitiativet för energieffektivitet, e2mp-i
- 2015
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Projektet har drivits som ett program för finansiering av forskning som ska utveckla ochdemonstrera tekniker som reducerar elenergiförbrukningen med 50% vid tillverkning avTMP och CTMP med bibehållna slutproduktegenskaper hos tryckpapper och kartong.Programmet är en del av skogsindustrins initiativ att under en tioårsperiod tillsammansmed svenska och norska finansiärer investera minst 200 Mkr för att nå detta radikalaeffektiviseringsmål. Ett uttalat mål för industriinitiativet är också att befästaforskningsnoderna vid FSCN i Sundsvall och PFI i Trondheim.Parallellt med Energimyndighetens finansiering, 30 Mkr, har Norges Forskningsråd satsat25 MNOK (2010‐14) i industriinitiativet, KK‐stiftelsen 36 MSEK (2011‐17) ochMittuniversitetet har finansierat12 MSEK. Industrins totala satsning kommer att överstiga100 MSEK redan vid utgången av 2017.Resultat från benchmarkingstudien BAT2012 av industrins modernaste TMP‐ och CTMPlinjersamt från demonstrationsskaleprojekt visas i rapporten. Projekten baseras delvis pågrundläggande forskningsprojekt genomförda inom FSCN´s KK‐stiftelse‐finansieradeforskningsprofil och projektet ”Filling the Gap” 31676‐, ISSN 1650‐5387 2014:57. Resultaten visar följande reduktionsnivåer; 28% TMP för news (Braviken), 14% TMP för SC(Kvarnsveden) och 21% CTMP för kartong (Skoghall).Utöver demoprojekten finns ytterligare tydliga potentialer beskrivna i övriga delprojekt:Processintensifiering och processmodifiering > 15%Processtabilitet via avancerad processanalys och reglering > 15%Kombinera effektivaste processavsnitt från benchmarking ca 25%Detta gör det troligt att det kommer att gå att i fullskaliga demonstrationsförsök validera50% elenergireduktion inom de tre produktområdena, förutsatt att fortsattforskningsfinansiering finns tillgänglig. Tre av de idéer till avknoppningsprojekt somframkommit under projektets gång har redan erhållit beslut om finansiering frånEnergimyndigheten 2015. Ytterligare projektförslag baserade på den här redovisadeforskningen kommer att ingå i ansökningar under 2016. Utöver energireduktion i själva TMP‐ och CTMP‐processerna har forskare vid FSCN lagt forskningsgrunden för hur manska kunna tillverka mycket starka förpackningsmaterial från dessa massatyper på ettenergieffektivt sätt. Även inom detta område kommer en ansökning omuppskalningsprojekt att skickas in.
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| 10. |
- Esberg, Anders, et al.
(författare)
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Oral Microbiota Profile in Patients with Anti-Neutrophil Cytoplasmic Antibody–Associated Vasculitis
- 2022
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Ingår i: Microorganisms. - : MDPI. - 2076-2607. ; 10:8
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Tidskriftsartikel (refereegranskat)abstract
- Microbiota has been associated with autoimmune diseases, with nasal Staphylococcus aureus being implicated in the pathogenesis of anti-neutrophil cytoplasmic antibody–associated vasculitis (AAV). Little is known about the role of oral microbiota in AAV. In this study, levels of IgG antibodies to 53 oral bacterial species/subspecies were screened using immunoblotting in plasma/serum in pre-symptomatic AAV-individuals (n = 85), matched controls, and established AAV-patients (n = 78). Saliva microbiota from acute-AAV and controls was sequenced from 16s rDNA amplicons. Information on dental status was extracted from a national register. IgG levels against oral bacteria were lower in established AAV versus pre-AAV and controls. Specifically, pre-AAV samples had, compared to controls, a higher abundance of periodontitis-associated species paralleling more signs of periodontitis in established AAV-patients than controls. Saliva microbiota in acute-AAV showed higher within-sample diversity but fewer detectable amplicon-sequence variants and taxa in their core microbiota than controls. Acute-AAV was not associated with increased abundance of periodontal bacteria but species in, e.g., Arthrospira, Staphylococcus, Lactobacillus, and Scardovia. In conclusion, the IgG profiles against oral bacteria differed between pre-AAV, established AAV, and controls, and microbiota profiles between acute AAV and controls. The IgG shift from a pre-symptomatic stage to established disease cooccurred with treatment of immunosuppression and/or antibiotics.
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| 11. |
- Fanidi, Anouar, et al.
(författare)
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Circulating vitamin D in relation to cancer incidence and survival of the head and neck and oesophagus in the EPIC cohort
- 2016
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Experimental and epidemiological data suggest that vitamin D play a role in pathogenesis and progression of cancer, but prospective data on head and neck cancer (HNC) and oesophagus cancer are limited. The European Prospective Investigation into Cancer and Nutrition (EPIC) study recruited 385,747 participants with blood samples between 1992 and 2000. This analysis includes 497 case-control pairs of the head and neck and oesophagus, as well as 443 additional controls. Circulating 25(OH)D3 were measured in pre-diagnostic samples and evaluated in relation to HNC and oesophagus cancer risk and post-diagnosis all-cause mortality. After controlling for risk factors, a doubling of 25(OH)D3 was associated with 30% lower odds of HNC (OR 0.70, 95% confidence interval [95% CI] 0.56-0.88, Ptrend = 0.001). Subsequent analyses by anatomical sub-site indicated clear inverse associations with risk of larynx and hypopharynx cancer combined (OR 0.55, 95CI% 0.39-0.78) and oral cavity cancer (OR 0.60, 95CI% 0.42-0.87). Low 25(OH)D3 concentrations were also associated with higher risk of death from any cause among HNC cases. No clear association was seen with risk or survival for oesophageal cancer. Study participants with elevated circulating concentrations of 25(OH)D3 had decreased risk of HNC, as well as improved survival following diagnosis.
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| 12. |
- Halldin, Anders, et al.
(författare)
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The effect of static strain
- 2012
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Ingår i: AstraTech World Congress, May 9-12, 2012, Göteborg, Sweden.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)
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| 13. |
- Johansson, David, et al.
(författare)
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alpha-Toxin of Staphylococcus aureus overcomes acquired cisplatin-resistance in malignant mesothelioma cells.
- 2008
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Ingår i: Cancer Letters. - : Elsevier BV. - 0304-3835 .- 1872-7980. ; 265:1, s. 67-75
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Tidskriftsartikel (refereegranskat)abstract
- alpha-Toxin (alpha-hemolysin) of Staphylococcus aureus is a pore-forming bacterial toxin which after caveolin-1-dependent assembly induces apoptosis in eukaryotic cells. We investigated if a sub-toxic concentration of staphylococcal alpha-toxin could enhance cisplatin-induced apoptosis and overcome acquired cisplatin-resistance in cultured malignant pleural mesothelioma (MPM) cells. MPM cells (P31wt) and a cisplatin-resistant sub-line (P31res) was incubated with alpha-toxin and/or cisplatin followed by determination of cell viability, apoptosis, and signaling pathways. P31res cells were more sensitive to alpha-toxin than P31 wt cells due to induction of apoptosis. A low-toxic concentration of alpha-toxin re-sensitized cisplatin P31res cytotoxicity by apoptosis-induced through the mitochondrial pathway without detectable activation of common up-stream apoptosis signaling proteins. The toxin/drug combination should be tested for cisplatin-resistant mesothelioma treatment.
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| 14. |
- Johansson, David, 1979-, et al.
(författare)
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Expression of verotoxin-1 receptor Gb3 in breast cancer tissue and verotoxin-1 signal transduction to apoptosis : Bacterial toxins, cancer treatment
- 2009
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Ingår i: BMC Cancer. - : Biomed Central. - 1471-2407. ; 26:9, s. 67-
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The prerequisite for the potential use of the bacterial toxin verotoxin-1 in the treatment of breast cancer was investigated by first determining the expression of its receptor Gb3 (CD77) in clinical breast cancer tissue specimens. We then examined the cytotoxicity and mechanism of apoptosis induction of Escherichia coli verotoxin-1 (VT-1) in two human breast cancer cell lines. METHODS: Immunohistochemistry for Gb3 expression was performed on cryostat section from 25 breast cancer specimens. The human breast cancer cell lines T47D and MCF-7 were screened for Gb3 expression by flow cytometry. Fluorescein diacetate and LDH release was used to determine cell viability after VT-1 exposure. Apoptosis was studied by measuring caspase activity and DNA-fragmentation. Signal transduction studies were performed on T47D cells with immunoblotting. RESULTS: Gb3 expression was detected in the vascular endothelial cells of all tumours specimens, and in tumour cells in 17 of the specimens. We found no associations between tumour cell Gb3-expression and age, tumour size, TNM-classification, histological type, hormone receptor expression, or survival time. T47D cells strongly expressed Gb3 and were sensitive to the cytotoxicity, caspase activation and DNA fragmentation by VT-1, whereas MCF-7 cells with faint Gb3-expression were insensitive to VT-1. VT-1 (0.01 - 5 microg/L) exposure for 72 h resulted in a small percentage of viable T47D cells whereas the cytotoxicity of cells pre-treated with 2 micromol/L D, L-treo-1-phenyl-2-palmitoylamino-3-morpholino-1-propanol (PPMP, an inhibitor of glucosylceramide synthesis) was eliminated (< or = 0.1 microg/L VT-1) or reduced (0.5 - 5 microg/L VT-1). VT-1 did not cause cellular LDH-release or cell cycle arrest. VT-1 induction of caspase-3 (0.1, 1, and 5 microg/L VT-1), -8, and -9 (1 and 5 microg/L VT-1) activity and DNA fragmentation of T47D cells was blocked by PPMP. Key components of MAP kinase signalling pathways that control mitochondrial function were investigated. VT-1 0.1 - 5 microg/L induced phosphorylation of JNK as well as MKK3/6 suggesting that survival signal pathways were overruled by VT-1-induced JNK activation leading to mitochondrial depolarization, caspase-9 activation and apoptosis. CONCLUSION: The high specificity and apoptosis-inducing properties of verotoxin-1 indicates that the toxin potentially may be used for treatment of Gb3-expressing breast cancer.
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| 15. |
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| 16. |
- Johansson, Per, et al.
(författare)
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Cerebrospinal Fluid Biomarkers for Alzheimer's Disease: Diagnostic Performance in a Homogeneous Mono-Center Population
- 2011
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Ingår i: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 24:3, s. 537-546
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Tidskriftsartikel (refereegranskat)abstract
- The cerebrospinal fluid (CSF) biomarkers amyloid-beta (A beta)(1-42), T-tau, and P-tau have good diagnostic accuracy for clinically diagnosed Alzheimer's disease (AD). However, in multi-center studies, the predictive values of the CSF biomarkers have been lower, possibly due to differences in procedures for lumbar puncture and CSF handling and storage, and to differences in patient populations, clinical evaluations, and diagnostic procedures. Here we investigate the diagnostic accuracy of CSF biomarkers in a well defined homogeneous mono-center population. We also evaluate an extended panel of amyloid related biomarkers. Sixty consecutive patients admitted for cognitive impairment to a memory clinic were recruited. The participants included patients with AD or mild cognitive impairment (MCI) diagnosed with AD upon follow-up (n = 32), patients with stable MCI (n = 13), patients with other dementias diagnosed at primary evaluation or upon follow-up (n = 15), and healthy controls (n = 20). CSF was analyzed for A beta(1-42), T-tau, P-tau, A beta(X-38), A beta(X-40), A beta(X-42), sA beta PP alpha, and sA beta PP beta. In multivariate analysis, the core biomarkers A beta(1-42), T-tau, and P-tau demonstrated a high ability to diagnose AD versus the combined groups of controls and stable MCI, with an area under the receiver operating characteristic curve (AUROC) of 0.97 (95% CI 0.93-1.00, p < 0.0001). The additional biomarkers only marginally increased AUROC to 0.98 (95% CI 0.95-1.00, p < 0.0001), this increase mainly mediated by A beta(X-42). In conclusion, CSF biomarkers A beta(1-42), T-tau, and P-tau have very high diagnostic accuracy in a well defined cohort of untreated patients, demonstrating the excellent potency of CSF biomarkers to identify pathological processes in AD when a stringent analytical protocol is used.
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| 17. |
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| 18. |
- Johansson, Per, 1966, et al.
(författare)
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Cerebrospinal fluid substance P concentrations are elevated in patients with Alzheimer's disease.
- 2015
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Ingår i: Neuroscience letters. - : Elsevier BV. - 1872-7972 .- 0304-3940. ; 609, s. 58-62
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Tidskriftsartikel (refereegranskat)abstract
- The neuropeptides substance P, orexin A (hypocretin-1) and neurotensin are signaling molecules that influence brain activity. We examined their cerebrospinal fluid (CSF) levels in a study population consisting of Alzheimer's disease (AD) dementia or mild cognitive impairment (MCI) diagnosed with AD dementia upon follow-up (n=32), stable MCI (SMCI, n=13), other dementias (n=15), and healthy controls (n=20). CSF substance P level was increased in AD patients compared to patients with other dementias and healthy controls (P<0.05 and P<0.01, respectively). Patients with other dementia or SMCI had lower CSF orexin A level than AD patients (both P<0.05) and marginally lower level than healthy controls (both P=0.05). CSF neurotensin level was similar in all groups. In the total study population (n=80), CSF substance P level correlated positively with CSF levels of T-tau and P-tau, and in AD patients (n=32), CSF substance P level correlated positively with CSF Aβ1-42 level. In conclusion, CSF substance P level was elevated in AD patients and correlated with CSF Aβ1-42 level, a well established marker of senile plaque pathology. The role of low CSF orexin A level in other dementias or SMCI needs to be explored in further studies.
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| 19. |
- Johansson, Per, 1966, et al.
(författare)
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Mild dementia is associated with increased adrenal secretion of cortisol and precursor sex steroids in women.
- 2011
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Ingår i: Clinical endocrinology. - : Wiley. - 1365-2265 .- 0300-0664. ; 75:3, s. 301-308
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Tidskriftsartikel (refereegranskat)abstract
- Context Sex steroid levels decrease with increasing age, but little is known whether this is of importance for the age-related decline in cognitive function. Design and patients A cross-sectional study of 50 (26 men) consecutive patients under primary evaluation of cognitive impairment (D group) and 18 (9 men) matched healthy controls (C group). Measurements Sex steroid and precursor levels were determined in serum and, when measurable, in cerebrospinal fluid (CSF) using gas chromatography/mass spectroscopy (GC-MS) or liquid chromatography/mass spectroscopy (LC-MS). Sex hormone binding globulin (SHBG) and cortisol concentrations were measured using conventional assays. Results Patients in the D group had higher 24-h urine cortisol levels and increased serum levels of dehydroepiandrosterone (DHEA) and its sulphate ester dihydroepiandrosterone sulphate (DHEAS), androsterone (ADT), and oestrone (E1) and its sulphate ester E1S, compared with the controls. When men and women were analysed separately, increased serum concentrations of E1 and E1S were observed in both D men and D women, whereas increased levels of other sex steroids and cortisol were seen only in D women. Conclusions In both D men and women, serum E1 and E1S levels were increased, whereas other changes were gender specific and only seen in D women. Further studies are needed to determine whether these changes are a cause of, or merely a consequence of, cognitive impairment in elderly subjects.
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| 20. |
- Johansson, Per, 1966, et al.
(författare)
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Reduced Cerebrospinal Fluid Concentration of Apolipoprotein A-I in Patients with Alzheimer's Disease.
- 2017
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Ingår i: Journal of Alzheimer's disease : JAD. - 1875-8908 .- 1387-2877. ; 59:3, s. 1017-1026
-
Tidskriftsartikel (refereegranskat)abstract
- Apolipoprotein E (ApoE) has been extensively studied in Alzheimer's disease (AD), but little is known of apolipoprotein A-I (ApoA-I) in cerebrospinal fluid (CSF).Plasma lipids as well as ApoA-I and ApoE in plasma and CSF were determined and related to Mini-Mental State Examination (MMSE) score, APOE genotype, and CSF AD biomarkers.Consecutive patients with AD (n=29), stable mild cognitive impairment (n=13), other dementias (n=14), and healthy controls (n=18) were included at a single center.AD patients had higher plasma triglycerides and lower CSF ApoA-I concentration than controls (both p<0.05). CSF ApoE concentration was reduced in other dementias (p<0.01). In AD as well as other dementias, the ratios between CSF and plasma concentrations of both ApoA-I and ApoE were lower than those in the controls. ApoA-I and ApoE in plasma and CSF were not influenced by APOEɛ4 allele distribution. In the total study population (n=74), CSF ApoA-I correlated positively with MMSE score (r=0.26, p<0.05) and negatively with CSF P-tau (r=-0.25, p<0.05). CSF ApoE correlated positively with CSF concentrations of T-tau and P-tau in the total study population and in AD patients.CSF ApoA-I was reduced in AD patients and associated with measures of cognitive function and AD disease status. The mechanisms underlying the decreased CSF:plasma ratios of ApoA-I and ApoE in AD and other dementias need to be explored in further studies.
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| 21. |
- Johansson, Per, 1966, et al.
(författare)
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Reduced cerebrospinal fluid concentration of interleukin-12/23 subunit p40 in patients with cognitive impairment.
- 2017
-
Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 12:5
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Tidskriftsartikel (refereegranskat)abstract
- The role of inflammation in Alzheimer's disease (AD) and other cognitive disorders is unclear. In a well-defined mono-center population, we measured cytokines and chemokines in paired serum and cerebrospinal fluid (CSF) samples.Consecutive patients with AD (n = 30), stable mild cognitive impairment (SMCI, n = 11), other dementias (n = 11), and healthy controls (n = 18) were included. None of the subjects was treated with glucocorticoids, cholinesterase inhibitors, or non-steroidal anti-inflammatory drugs. Serum and CSF concentrations of interleukin-6 (IL-6), IL-8, IL-12/23 p40, IL-15, IL-16, vascular endothelial growth factor-A (VEGF-A), and three chemokines were measured using a multiplex panel.After correction for multiple comparisons, only CSF IL-12/23 p40 concentration differed significantly between the total patient group (n = 52) and controls (n = 18; p = 0.002). Further analyses showed that CSF IL-12/23 p40 concentration was decreased in all patient subgroups (AD, other dementias, and SMCI) compared to healthy controls (p < 0.01, p < 0.05, and p < 0.05, respectively). In the total study population (n = 70), CSF IL-12/23 p40 concentrations correlated positively with CSF concentrations of β-amyloid1-42 (Aβ1-42) and phosphorylated tau protein (P-tau) whereas in AD patients (n = 30), CSF IL-12/23 p40 only correlated positively with CSF P-Tau (r = 0.46, p = 0.01).Most cytokines and chemokines were similar in patients and controls, but CSF IL-12/23 subunit p40 concentration was decreased in patients with cognitive impairment, and correlated with markers of AD disease status. Further studies are needed to evaluate the role of CSF IL-12/23 p40 in other dementias and SMCI.
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| 22. |
- Johansson, Per, et al.
(författare)
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Reduced cerebrospinal fluid level of thyroxine in patients with Alzheimer's disease
- 2013
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Ingår i: Psychoneuroendocrinology. - : Elsevier BV. - 1873-3360 .- 0306-4530. ; 38:7, s. 1058-1066
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Tidskriftsartikel (refereegranskat)abstract
- Background: Little is known of the association between thyroid hormones in the central nervous system and Alzheimer's disease (AD). We determined thyroid hormone levels in serum and cerebrospinal fluid (CSF) in a well-defined homogeneous mono-center population. Methods: Fifty-nine consecutive patients under primary evaluation for cognitive impairment were recruited. The participants included patients with AD or mild cognitive impairment (MCI) diagnosed with AD upon follow-up (n = 31), patients with stable MCI (SMCI, n = 13), patients with other dementias (n = 15), and healthy controls (n = 19). Thyroid hormones in serum and CSF and AD biomarkers in CSF were analyzed using established immunochemical assays. Cognitive impairment was estimated using mini-mental state examination (MMSE). Results: Serum levels of free and total thyroxine (T4) and triiodothyronine (T3) were similar in all groups whereas a marginal increase in serum thyroid-stimulating hormone (TSH) level was observed in the AD patients. The CSF level of total T4 was decreased in patients with AD and other dementias compared to SMCI (both P = 0.01) and healthy controls (both P = 0.001), whereas CSF levels of TSH and total T3 were unchanged. In the total study population, CSF total 14 level correlated positively with MMSE score (r = 0.26, P < 0.05) and negatively with CSF total-tau (T-Tau) level (r = -0.23, P < 0.05). Conclusion: Patients with AD as well as other dementias had signs of mild brain hypothyroidism, which could only to a small extent be detected in serum values. (C) 2012 Elsevier Ltd. All rights reserved.
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| 23. |
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| 24. |
- Mattsson, Niklas, 1979, et al.
(författare)
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Cerebrospinal Fluid Microglial Markers in Alzheimer's Disease: Elevated Chitotriosidase Activity but Lack of Diagnostic Utility
- 2011
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Ingår i: NeuroMolecular Medicine. - : Springer Science and Business Media LLC. - 1535-1084 .- 1559-1174. ; 13:2, s. 151-159
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Tidskriftsartikel (refereegranskat)abstract
- Activated microglial cells, which are the resident macrophages of the central nervous system, surround amyloid beta-plaques in Alzheimer's disease (AD) brains. Inflammation including microglial activation may contribute in AD pathogenesis, and biomarkers for this process may thus be of value to study AD pathogenesis and might facilitate development of therapies targeting these cells. We therefore examined cerebrospinal fluid (CSF) biomarkers in patients with AD, other dementias, mild cognitive impairment and in healthy controls. Samples were analyzed for markers with known association to macrophage activity, including chitotriosidase, YKL-40 (CHI3L1, HC gp-39) and chemokine CC motif ligand 2 (CCL2, MCP1). Patients with AD had higher chitotriosidase activity than controls and patients with stable mild cognitive impairment, consistent with the presence of activated microglial cells in AD brains, but with large overlaps between groups. CCL2 and YKL-40 concentrations did not differ among groups. Microglial markers are unlikely to be useful for AD diagnosis, but might be useful for identification of distinct subgroups of patients, and for the development and implementation of drugs targeting microglial pathology.
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| 25. |
- Mattsson, Niklas, 1979, et al.
(författare)
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Converging Pathways of Chromogranin and Amyloid Metabolism in the Brain
- 2010
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Ingår i: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 20:4, s. 1039-1048
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Tidskriftsartikel (refereegranskat)abstract
- Much is unknown regarding the regulation of Alzheimer-related amyloid-beta protein precursor (A beta PP)-processing in the human central nervous system. It has been hypothesized that amyloidogenic A beta PP-processing preferentially occurs in the regulated secretory pathway of neurons. To test this hypothesis we looked for correlations of A beta PP-derived molecules in cerebrospinal fluid (CSF) with chromogranin (Cg) derived peptides, representing the regulated secretion. Patients with Alzheimer's disease (AD, N = 32), multiple sclerosis (MS, N = 50), and healthy controls (N = 70) were enrolled. CSF was analyzed for the amyloid peptides A beta(1-42), A beta(x-42), A beta(x-40), A beta(x-38), alpha-cleaved soluble A beta PP (sA beta PP alpha), beta-cleaved soluble A beta PP (sA beta PP beta), and peptides derived from CgB and SgII (Secretogranin-II, CgC). We investigated CSF levels of the protease BACE1, which processes A beta PP into A beta, in relation to Cg-levels. Finally, we measured Cg levels in cell media from untreated and BACE1-inhibited SH-SY5Y human neuroblastoma cells. CSF Cg levels correlated to sA beta PP and A beta peptides in AD, MS, and controls, and to CSF BACE1. Cell medium from BACE1-inhibited cells had decreased CgB levels. These results suggest that a large part of A beta PP in the human central nervous system is processed in the regulated secretory pathway of neurons.
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| 26. |
- Movérare-Skrtic, Sofia, et al.
(författare)
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Leukocyte Telomere Length (LTL) is reduced in stable mild cognitive impairment but low LTL is not associated with conversion to Alzheimer's Disease: A pilot study
- 2012
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Ingår i: Experimental Gerontology. - : Elsevier BV. - 1873-6815 .- 0531-5565. ; 47:2, s. 179-182
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Tidskriftsartikel (refereegranskat)abstract
- Leukocyte telomere length (LTL) is associated with the aging process and may be related to cognitive aging. Previous studies have shown conflicting results whether LTL is affected in patients with Alzheimer's disease (AD). In this pilot study, we investigated LTL in a well-defined homogeneous mono-center population. Sixty consecutive patients admitted for cognitive impairment to a memory clinic were recruited. The participants included patients with AD or mild cognitive impairment (MCI) diagnosed with AD upon follow-up (n=32), patients with stable MCI (n=13), patients with other dementias diagnosed at primary evaluation or upon follow-up (n=15), and healthy controls (n=20). LTL was determined using a quantitative PCR assay. Patients with AD had similar LTL as healthy controls. Patients with stable MCI had reduced LTL both compared to AD patients (p=0.02) and controls (p=0.008). Subanalyses within the AD group showed that patients with MCI that later converted to AD had similar LTL as patients with clinical diagnosis of AD at primary evaluation and healthy controls whereas the LTL was longer compared to the stable MCI group (p=0.02). There were no correlations between LTL and the core AD biomarkers A beta(1-42), T-tau and P-tau. In conclusion, in this pilot study, patients with AD or MCI that later converted to AD had similar LTL as healthy controls. Patients with stable MCI that did not progress to dementia had reduced LTL compared to controls, which might suggest a more marked biological aging as a cause of the cognitive symptoms in this group. (C) 2011 Elsevier Inc. All rights reserved.
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| 27. |
- Rosén, Christoffer, 1986, et al.
(författare)
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Discriminatory analysis of biochip-derived protein patterns in CSF and plasma in neurodegenerative diseases
- 2011
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Ingår i: Frontiers in Aging Neuroscience. - : Frontiers Media SA. - 1663-4365. ; 3
-
Tidskriftsartikel (refereegranskat)abstract
- The role of biomarkers in neurodegenerative diseases has been emphasized by recent research. Future clinical demands for identifying diseases at an early stage may render them essential. The aim of this pilot study was to test the analytical performance of two multiplex assays of cerebral markers on a well-defined clinical material consisting of patients with various neurodegenerative diseases. We measured 10 analytes in plasma and cerebrospinal fluid (CSF) from 60 patients suffering from Alzheimer's disease (AD), vascular dementia, frontotemporal dementia, dementia with Lewy bodies, or mild cognitive impairment, as well as 20 cognitively healthy controls. We used the Randox biochip-based Evidence Investigator™ system to measure the analytes. We found it possible to measure most analytes in both plasma and CSF, and there were some interesting differences between the diagnostic groups, although with large overlaps. CSF heart-type fatty acid-binding protein was increased in AD. Glial fibrillary acidic protein and neutrophil gelatinase-associated lipocalin in CSF and D-dimer in plasma were elevated in patients with cerebrovascular disease. A multivariate statistical analysis revealed that the pattern of analytes could help to differentiate the conditions, although more studies are required to verify this.
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| 28. |
- Åberg, Daniel, 1973, et al.
(författare)
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Increased Cerebrospinal Fluid Level of Insulin-like Growth Factor-II in Male Patients with Alzheimer's Disease
- 2015
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Ingår i: Journal of Alzheimers Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 48:3, s. 637-646
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Tidskriftsartikel (refereegranskat)abstract
- Background: Insulin-like growth factor-II (IGF-II) is important for brain development. Although IGF-II is abundant also in adult life, little is known of the role of IGF-II in Alzheimer's disease (AD). Objective and methods: This was a cross-sectional study of 60 consecutive patients under primary evaluation of cognitive impairment and 20 healthy controls. The patients had AD dementia or mild cognitive impairment (MCI) diagnosed with AD dementia upon follow-up (n = 32), stable MCI (SMCI, n = 13), or other dementias (n = 15). IGF-II, IGF-binding protein-1 (IGFBP-1), and IGFBP-2 were analyzed in serum and cerebrospinal fluid (CSF). Results: Levels of IGF-II, IGFBP-1, and IGFBP-2 were similar in all groups in the total study population. Gender-specific analyses showed that in men (n = 40), CSF IGF-II level was higher in AD compared to SMCI and controls (p < 0.01 and p < 0.05, respectively). Furthermore, CSF IGFBP-2 levelwas increased inADmen versus SMCI men (p < 0.01) and tended to be increased versus control men (p = 0.09). There were no between-group differences in women (n = 40). In the total study population (n = 80) as well as in men (n = 40), CSF levels of IGF-II and IGFBP-2 correlated positively with CSF levels of the AD biomarkers total-tau and phosphorylated tau protein. Conclusion: In men, but not women, in the early stages of AD, CSF IGF-II level was elevated, and CSF IGFBP-2 level tended to be increased, compared to healthy controls.
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| 29. |
- Abad, Alberto, 1972, et al.
(författare)
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The use of iron oxide as oxygen carrier in a chemical-looping reactor
- 2007
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Ingår i: Fuel. - : Elsevier BV. - 0016-2361. ; 86:7-8, s. 1021-1035
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Tidskriftsartikel (refereegranskat)abstract
- Chemical-looping combustion (CLC) is a method for the combustion of fuel gas with inherent separation of carbon dioxide. This technique involves the use of two interconnected reactors, an air reactor and a fuel reactor. The oxygen demanded in the fuel combustion is supplied by a solid oxygen carrier, which circulates between both reactors. Fuel gas and air are never mixed and pure CO2 can be obtained from the flue gas exit. This paper presents the results from the use of an iron-based oxygen-carrier in a continuously operating laboratory CLC unit, consisting of two interconnected fluidized beds. Natural gas or syngas was used as fuel, and the thermal power was between 100 and 300 W. Tests were performed at four temperatures: 1073, 1123, 1173 and 1223 K. The prototype was successfully operated for all tests and stable conditions were maintained during the combustion. The same particles were used during 60 h of hot fluidization conditions, whereof 40 h with combustion. The combustion efficiency of syngas was high, about 99% for all experimental conditions. However, in the combustion tests with natural gas, there was unconverted methane in the exit flue gases. Higher temperature and lower fuel flows increase the combustion efficiency, which ranged between 70% and 94% at 1123 K. No signs of agglomeration or mass loss were detected, and the crushing strength of the oxygen carrier particles did not change significantly. Complementary experiments in a batch fluidized bed were made to compare the reactivity of the oxygen carrier particles before and after the 40 h of operation, but the reactivity of the particles was not affected significantly.
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| 30. |
- Adolfsson, Jan, et al.
(författare)
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Clinical characteristics and primary treatment of prostate cancer in Sweden between 1996 and 2005
- 2007
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Ingår i: Scandinavian Journal of Urology and Nephrology. - : Informa UK Limited. - 0036-5599 .- 1651-2065. ; 41:6, s. 456-477
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The incidence of prostate cancer is rising rapidly in Sweden and there is a need to better understand the pattern of diagnosis, tumor characteristics and treatment. MATERIAL AND METHODS: Between 1996 and 2005, all new cases of adenocarcinoma of the prostate gland were intended to be registered in the National Prostate Cancer Register (NPCR). This register contains information on diagnosing unit, date of diagnosis, cause of diagnosis, tumor grade, tumor stage according to the TNM classification in force, serum prostate-specific antigen (PSA) levels at diagnosis and primary treatment given within the first 6 months after diagnosis. RESULTS: In total, 72,028 patients were registered, comprising >97% of all pertinent incident cases of prostate cancer in the Swedish Cancer Register (SCR). During the study period there was a considerable decrease in median age at the time of diagnosis, a stage migration towards smaller tumors, a decrease in median serum PSA values at diagnosis, a decrease in the age-standardized incidence rate of men diagnosed with distant metastases or with a PSA level of > 100 ng/ml at diagnosis and an increase in the proportion of tumors with Gleason score <6. Relatively large geographical differences in the median age at diagnosis and the age-standardized incidence of cases with category T1c tumors were observed. Treatment with curative intent increased dramatically and treatment patterns varied according to geographical region. In men with localized tumors and a PSA level of <20 ng/ml at diagnosis, expectant treatment was more commonly used in those aged > or =75 years than in those aged <75 years. Also, the pattern of endocrine treatment varied in different parts of Sweden. CONCLUSIONS: All changes in the register seen over time are consistent with increased diagnostic activity, especially PSA testing, resulting in an increased number of cases with early disease, predominantly tumors in category T1c. The patterns of diagnosis and treatment of prostate cancer vary considerably in different parts of Sweden. The NPCR continues to be an important source for research, epidemiological surveillance of the incidence, diagnosis and treatment of prostate cancer.
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| 31. |
-
Aggregatibacter actinomycetemcomitans : Gram-Negative Bacterial Pathogen
- 2020
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Samlingsverk (redaktörskap) (refereegranskat)abstract
- Aggregatibacter actinomycetemcomitans, a member of the Gram-negative taxonomic family Pasteurellaceae, has attracted considerable attention as a potentially important pathogen in specific forms of periodontal disease and has earned a reputation as a member of the HACEK group of bacteria associated with some cases of infective endocarditis. The bacterium has acquired an impressive virulence-related armamentarium, including two well-characterized cytotoxins, exoenzymes, adhesins, and signaling molecules that promote its colonization and the perturbation of the tissues, structural cells, and inflammatory cells of the human oral cavity. This Special Issue focuses on the properties and activities of A. actinomycetemcomitans that promote its function as an infectious agent, that is, its ability to target specific host populations and define its interactions with specific mucosal tissues and cells. The objective is to present a complete picture of the participation of this bacterium in disease by presenting both in vitro and in vivo experimental and clinical studies. A comprehensive view of the contribution of this bacterium to the mechanisms of infection and disease should also provide a basis for the development of new control strategies that move beyond the classical antibiotics.
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| 32. |
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| 33. |
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| 34. |
- Ahlström, Christer, 1977-, et al.
(författare)
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Noninvasive investigation of blood pressure changes using the pulse wave transit time : A novel approach in the monitoring of hemodialysis patients
- 2005
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Ingår i: Journal of Artificial Organs. - : Springer Science and Business Media LLC. - 1434-7229 .- 1619-0904. ; 8:3, s. 192-197
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Tidskriftsartikel (refereegranskat)abstract
- Severe blood pressure changes are well known in hemodialysis. Detection and prediction of these are important for the well-being of the patient and for optimizing treatment. New noninvasive methods for this purpose are required. The pulse wave transit time technique is an indirect estimation of blood pressure, and our intention is to investigate whether this technique is applicable for hemodialysis treatment. A measurement setup utilizing lower body negative pressure and isometric contraction was used to simulate dialysis-related blood pressure changes in normal test subjects. Systolic blood pressure levels were compared to different pulse wave transit times, including and excluding the cardiac preejection period. Based on the results of these investigations, a pulse wave transit time technique adapted for dialysis treatment was developed and tried out on patients. To determine systolic blood pressure in the normal group, the total pulse wave transit time was found most suitable (including the cardiac preejection period). Correlation coefficients were r = 0.80 ± 0.06 (mean ± SD) overall and r = 0.81 ± 0.16 and r = 0.09 ± 0.62 for the hypotension and hypertension phases, respectively. When applying the adapted technique in dialysis patients, large blood pressure variations could easily be detected when present. Pulse wave transit time is correlated to systolic blood pressure within the acceptable range for a trend-indicating system. The method's applicability for dialysis treatment requires further studies. The results indicate that large sudden pressure drops, like those seen in sudden hypovolemia, can be detected. © The Japanese Society for Artificial Organs 2005.
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| 35. |
- Akkaoui, Sanae, et al.
(författare)
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Chemical Composition, Antimicrobial activity, in Vitro Cytotoxicity and Leukotoxin Neutralization of Essential Oil from Origanum vulgare against Aggregatibacter actinomycetemcomitans
- 2020
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Ingår i: Pathogens. - Basel : MDPI. - 2076-0817. ; 9:3
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Tidskriftsartikel (refereegranskat)abstract
- In this study, the essential oil of Origanum vulgare was evaluated for putative antibacterial activity against six clinical strains and five reference strains of Aggregatibacter actinomycetemcomitans, in comparison with some antimicrobials. The chemical composition of the essential oil was analyzed, using chromatography (CG) and gas chromatography-mass spectrometry coupled (CG-MS). The major compounds in the oil were Carvacrol (32.36%), α-terpineol (16.70%), p-cymene (16.24%), and Thymol (12.05%). The antimicrobial activity was determined by an agar well diffusion test. A broth microdilution method was used to study the minimal inhibitory concentration (MIC). The minimal bactericidal concentration (MBC) was also determined. The cytotoxicity of the essential oil (IC50) was <125 µg/mL for THP-1 cells, which was high in comparison with different MIC values for the A. actinomycetemcomitans strains. O. vulgare essential oil did not interfere with the neutralizing capacity of Psidium guajava against the A. actinomycetemcomitans leukotoxin. In addition, it was shown that the O. vulgare EO had an antibacterial effect against A. actinomycetemcomitans on a similar level as some tested antimicrobials. In view of these findings, we suggest that O.vulgare EO may be used as an adjuvant for prevention and treatment of periodontal diseases associated to A. actinomycetemcomitans. In addition, it can be used together with the previously tested leukotoxin neutralizing Psidium guajava.
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| 36. |
- Anders, Halldin, et al.
(författare)
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Improved osseointegration and interlocking capacity with dual acid treated implants: a rabbit study.
- 2016
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Ingår i: Clinical Oral Implants Research. - : Wiley. - 0905-7161 .- 1600-0501. ; 27, s. 22-30
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Tidskriftsartikel (refereegranskat)abstract
- Aim To investigate how osseointegration is affected by different nano- and microstructures. The hypothesis was that the surface structure created by dual acid treatment (AT-1), applied on a reduced topography, might achieve equivalent biomechanical performance as a rougher surface treated with hydrofluoric acid (HF). Materials and methods In a preclinical rabbit study, three groups (I, II, and III) comprised of test and control implants were inserted in 30 rabbits. The microstructures of the test implants were either produced by blasting with coarse (I) or fine (II) titanium particles or remained turned (III). All test implants were thereafter treated with AT-1 resulting in three different test surfaces. The microstructure of the control implants was produced by blasting with coarse titanium particles thereafter treated with HF. The surface topography was characterized by interferometry. Biomechanical (removal torque) and histomorphometric (bone–implant contact; bone area) performances were measured after 4 or 12 weeks of healing. Results Removal torque measurement demonstrated that test implants in group I had an enhanced biomechanical performance compared to that of the control despite similar surface roughness value (Sa). At 4 weeks of healing, group II test implants showed equivalent biomechanical performance to that of the control, despite a decreased Sa value. Group III test implants showed decreased biomechanical performance to that of the control. Conclusions: The results of the present study suggest that nano- and microstructure alteration by AT-1 on a blasted implant might enhance the initial biomechanical performance, while for longer healing time, the surface interlocking capacity seems to be more important.
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| 37. |
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| 38. |
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| 39. |
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| 40. |
- Behnam-Motlagh, Parviz, et al.
(författare)
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Verotoxin-1 Treatment or Manipulation of its Receptor Globotriaosylceramide (Gb3) for Reversal of Multidrug Resistance to Cancer Chemotherapy
- 2010
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Ingår i: Toxins. - Basel : MDPI. - 2072-6651. ; 2:10, s. 2467-2477
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Forskningsöversikt (refereegranskat)abstract
- A major problem with anti-cancer drug treatment is the development of acquired multidrug resistance (MDR) of the tumor cells. Verotoxin-1 (VT-1) exerts its cytotoxicity by targeting the globotriaosylceramide membrane receptor (Gb3), a glycolipid associated with multidrug resistance. Gb3 is overexpressed in many human tumors and tumor cell lines with inherent or acquired MDR. Gb3 is co-expressed and interplays with the membrane efflux transporter P-gp encoded by the MDR1 gene. P-gp could act as a lipid flippase and stimulate Gb3 induction when tumor cells are exposed to cancer chemotherapy. Recent work has shown that apoptosis and inherent or acquired multidrug resistance in Gb3-expressing tumors could be affected by VT-1 holotoxin, a sub-toxic concentration of the holotoxin concomitant with chemotherapy or its Gb3-binding B-subunit coupled to cytotoxic or immunomodulatory drug, as well as chemical manipulation of Gb3 expression. The interplay between Gb3 and P-gp thus gives a possible physiological approach to augment the chemotherapeutic effect in multidrug resistant tumors.
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| 41. |
- Belibasakis, Georgios N, et al.
(författare)
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Cytolethal distending toxin upregulates RANKL expression in Jurkat T-cells.
- 2008
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Ingår i: APMIS : acta pathologica, microbiologica, et immunologica Scandinavica. - Copenhagen : Wiley. - 0903-4641 .- 1600-0463. ; 116:6, s. 499-506
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Tidskriftsartikel (refereegranskat)abstract
- Cytolethal distending toxin, a bacterial exotoxin produced by a number of Gram-negative species, causes growth arrest and morphological alterations in host cells. Among these species are Haemophilus ducreyi, the etiological agent of chancroid, and the periodontal pathogen Aggregatibacter actinomycetemcomitans, highly implicated in localized aggressive periodontitis. CDT induces receptor activator of NF-kappaB ligand (RANKL) expression in periodontal fibroblasts, the key bone-resorbing cytokine. T-cells are actively involved in localized inflammation-induced bone destruction, including periodontitis. The aim of this study was to investigate the effects of purified CDT on the expression of RANKL and its decoy receptor osteoprotegerin (OPG), in the Jurkat T-cell line. Quantitative real-time PCR indicated that 100 pg/ml of purified H. ducreyi CDT upregulated RANKL mRNA expression by 2.2-fold, after 24 h of exposure. This increase was corroborated by a 2.0-fold increase in RANKL protein release, as determined by ELISA. OPG was not detected in this experimental system. In conclusion, CDT enhances RANKL expression in T-cells, denoting that these cells are a potential target for the toxin and strengthening the potential link between this virulence factor and mechanisms associated with localized bone resorption.
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| 42. |
- Belibasakis, Georgios N., et al.
(författare)
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Periodontal microbiology and microbial etiology of periodontal diseases : Historical concepts and contemporary perspectives
- 2023
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Ingår i: Periodontology 2000. - : Wiley-Blackwell. - 0906-6713 .- 1600-0757.
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Tidskriftsartikel (refereegranskat)abstract
- This narrative review summarizes the collective knowledge on periodontal microbiology, through a historical timeline that highlights the European contribution in the global field. The etiological concepts on periodontal disease culminate to the ecological plaque hypothesis and its dysbiosis-centered interpretation. Reference is made to anerobic microbiology and to the discovery of select periodontal pathogens and their virulence factors, as well as to biofilms. The evolution of contemporary molecular methods and high-throughput platforms is highlighted in appreciating the breadth and depth of the periodontal microbiome. Finally clinical microbiology is brought into perspective with the contribution of different microbial species in periodontal diagnosis, the combination of microbial and host biomarkers for this purpose, and the use of antimicrobials in the treatment of the disease.
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| 43. |
- Belibasakis, Georgios N, et al.
(författare)
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Virulence and Pathogenicity Properties of Aggregatibacter actinomycetemcomitans
- 2019
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Ingår i: Pathogens. - Basel : MDPI. - 2076-0817. ; 8:4
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Tidskriftsartikel (refereegranskat)abstract
- Aggregatibacter actinomycetemcomitans is a periodontal pathogen colonizing the oral cavity of a large proportion of the human population. It is equipped with several potent virulence factors that can cause cell death and induce or evade inflammation. Because of the large genetic diversity within the species, both harmless and highly virulent genotypes of the bacterium have emerged. The oral condition and age, as well as the geographic origin of the individual, influence the risk to be colonized by a virulent genotype of the bacterium. In the present review, the virulence and pathogenicity properties of A. actinomycetemcomitans will be addressed.
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| 44. |
- Berg, Linda, 1961, et al.
(författare)
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Characterisation of Cancer Support and Rehabilitation Programmes: A Swedish Multiple Case Study
- 2014
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Ingår i: The open nursing journal. - : Bentham Science Publishers Ltd.. - 1874-4346. ; 8, s. 1-7
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Tidskriftsartikel (refereegranskat)abstract
- Cancer support and rehabilitation are suggested to be an integral part of cancer care strategies. This study focuses on comparativeness of cancer support and rehabilitation programmes. The aim of this study was to analyse available cancer support and rehabilitation programmes in Sweden presented as complementary to cancer rehabilitation at cancer clinics. A multiple case study design was chosen in order to inquire the small number of existing supportive and rehabilitative cancer programmes. Based on the structures, processes and outcomes of the nine included programmes, three types of cancer support and rehabilitation programmes were identified: multimodal rehabilitation, comprehensive cancer support and art therapy. Cancer support and rehabilitation programmes offer a variety of activities and therapies which are highly valuable and relevant for people with cancer. The typology of cancer support and rehabilitation programmes and comparability between programmes need further inquiry.
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| 45. |
- Bergh, Ingrid, 1956, et al.
(författare)
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Pain and its relation to cognitive function and depressive symptoms: a Swedish population study of 70-year-old men and women.
- 2003
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Ingår i: Journal of pain and symptom management. - : Elsevier. - 0885-3924 .- 1873-6513. ; 26:4, s. 903-12
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to investigate the prevalence of pain and its characteristics, and to examine the association of pain with cognitive function and depressive symptoms, in a representative sample of 70-year-old men and women. Data were collected within the gerontological and geriatric population studies in G?teborg, Sweden (H-70). A sample of 124 men and 117 women living in the community took part in the study. A questionnaire was applied which included four different aspects of pain experience: prevalence, frequency of episodes of pain, duration and number of locations. In close connection to this, depressive symptoms were assessed using the Center for Epidemiological Studies Depression Scale. The prevalence of pain during the last 14 days was higher in women (79%; n=91) than in men (53%; n=65) (P<0.001). Women (68%; n=78) also reported pain that had lasted for >6 months to a greater extent than men (38%; n=46) (P<0.001). The frequency of episodes of pain was also higher among women, 64% (n=74) reporting daily pain or pain several days during the last 14 days while 37% of the men (n=45) did so (P<0.001). Women (33%, n=38) also reported pain experience from >/=3 locations more often than men (11%; n=13) (P<0.001). On the other hand, the association between depressive symptoms and pain experience was more evident in men than in women. Women were taking significantly more antidepressants compared to men (P<0.03). The results show that pain is common in 70-year-old people and especially in women. However, associations between depressive symptoms and the four aspects of pain experience were more pronounced among men.
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| 46. |
- Birkeholm Jensen, Anne, et al.
(författare)
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Prevalence of Aggregatibacter actinomycetemcomitans and Periodontal Findings among 14 to 15-Year Old Danish Adolescents : A Descriptive Cross-Sectional Study
- 2020
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Ingår i: Pathogens. - Basel : MDPI. - 2076-0817. ; 9:12
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Tidskriftsartikel (refereegranskat)abstract
- Aggregatibacter actinomycetemcomitans (Aa) is a keystone pathogen associated with periodontitis in adolescents. The knowledge on the prevalence of Aa and periodontitis among adolescents in Northern Europe is sparse. A total of 525 14- to 15-year-old adolescents from the municipality of Aarhus, Denmark, underwent a full-mouth clinical examination. Plaque score (PS), bleeding on probing (BOP), probing pocket depth (PPD), and clinical attachment loss (CAL) were recorded. Subgingival plaque samples (SPS) and stimulated saliva samples (SSS) were collected and analyzed for the presence of JP2 and non-JP2 genotypes of Aa using real-time PCR. A total of 70 (13.3%) individuals were positive for Aa, with 17 found in SPS, 19 in SSS, and 35 in both. The highly leukotoxic JP2 genotype of Aa was not detected. The individuals positive for Aa in both SPS and SSS had poorer periodontal outcomes (PPD and CAL) than individuals without Aa and individuals carrying Aa in either SPS or SSS only. In conclusion, 13% of 14- to 15-year-old Danish adolescents were positive for Aa, and the presence of Aa in both SPS and SSS was associated with poorer periodontal outcomes.
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| 47. |
- Boles, Usama, et al.
(författare)
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Cytokine Disturbances in Coronary Artery Ectasia Do Not Support Atherosclerosis Pathogenesis
- 2018
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Ingår i: International Journal of Molecular Sciences. - Basel, Switzerland : MDPI. - 1661-6596 .- 1422-0067. ; 19:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Coronary artery ectasia (CAE) is a rare disorder commonly associated with additional features of atherosclerosis. In the present study, we aimed to examine the systemic immune-inflammatory response that might associate CAE.METHODS: Plasma samples were obtained from 16 patients with coronary artery ectasia (mean age 64.9 ± 7.3 years, 6 female), 69 patients with coronary artery disease (CAD) and angiographic evidence for atherosclerosis (age 64.5 ± 8.7 years, 41 female), and 140 controls (mean age 58.6 ± 4.1 years, 40 female) with normal coronary arteries. Samples were analyzed at Umeå University Biochemistry Laboratory, Sweden, using the V-PLEX Pro-Inflammatory Panel 1 (human) Kit. Statistically significant differences (p < 0.05) between patient groups and controls were determined using Mann-Whitney U-tests.RESULTS: The CAE patients had significantly higher plasma levels of INF-γ, TNF-α, IL-1β, and IL-8 (p = 0.007, 0.01, 0.001, and 0.002, respectively), and lower levels of IL-2 and IL-4 (p < 0.001 for both) compared to CAD patients and controls. The plasma levels of IL-10, IL-12p, and IL-13 were not different between the three groups. None of these markers could differentiate between patients with pure (n = 6) and mixed with minimal atherosclerosis (n = 10) CAE.CONCLUSIONS: These results indicate an enhanced systemic pro-inflammatory response in CAE. The profile of this response indicates activation of macrophages through a pathway and trigger different from those of atherosclerosis immune inflammatory response.
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| 48. |
- Bougas, K., et al.
(författare)
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Effects of Porphyromonas gingivalis surface-associated material on osteoclast formation
- 2013
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Ingår i: Odontology. - : Springer Science and Business Media LLC. - 1618-1247 .- 1618-1255. ; 101:2, s. 140-149
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Tidskriftsartikel (refereegranskat)abstract
- Porphyromonas gingivalis strongly correlates with periodontitis, but the underlying mechanisms causing dentoalveolar bone resorption are not fully understood. As contradictory effects of P. gingivalis on osteoclastogenesis have been reported, this study investigates the effect of P. gingivalis extract on osteoclast formation. Osteoclast formation in mouse bone marrow (MBM) cell cultures and RAW 264.7 cells was stimulated by nuclear factor-kappa B ligand (RANKL) or parathyroid hormone (PTH). Cells were cultured with and without P. gingivalis surface-associated material and phenotypic characteristics were examined using microscopy, flow cytometry, and RT-PCR. P. gingivalis significantly decreased osteoclast formation and the expression of osteoclast phenotypic markers in PTH-stimulated MBM cultures. Additionally, P. gingivalis inhibited expression of osteoclast differentiation factors and stimulated expression of the mouse macrophage marker F4/80. The presence of P. gingivalis in RANKL-stimulated MBM cultures and RAW 264.7 cells inhibited osteoclastogenesis. Interestingly, a transient exposure with P. gingivalis before PTH stimulation increased osteoclastogenesis in MBM cultures. Flow cytometric analyses of cells transiently exposed to P. gingivalis demonstrated an increased proportion of potential osteoclast precursor cells. We conclude that a transient exposure of MBM cultures to P. gingivalis increases the number of osteoclast precursors and osteoclast formation, whereas a prolonged exposure completely abolishes osteoclastogenesis.
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| 49. |
- Claesson, Rolf, et al.
(författare)
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Age-related subgingival colonization of aggregatibacter actinomycetemcomitans, porphyromonas gingivalis and parvimonas micra : a pragmatic microbiological retrospective report
- 2023
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Ingår i: Microorganisms. - Basel : MDPI. - 2076-2607. ; 11:6
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to compare data about the prevalence and proportions of the bacterial species Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, and Parvimonas micra in periodontitis pocket samples collected from young, <35 years, and old, >35-year-old patients, YP and OP, respectively. The results from the analyses of a total of 3447 subgingival plaque samples analyzed for clinical diagnosis purposes by cultivation regarding the proportions of these species were collected from a database and elucidated. The prevalence of A. actinomycetemcomitans was found to be more than twice as high (OR = 2.96, 95% CI; 2.50–3.50) in samples from the younger (42.2%) than the older group (20.4%) (p < 0.001). The prevalence of P. micra was significantly lower in samples from the younger age group (OR = 0.43, 95%) (p < 0.001), whereas P. gingivalis was similarly distributed (OR = 0.78, 95%) in the two age groups (p = 0.006). A similar pattern was noticed for A. actinomycetemcomitans and P. gingivalis when high proportions (>50%) of the samples of these bacterial species were elucidated. In contrast, the proportion of samples containing >50% with P. micra was lower compared with the two other bacterial species. Furthermore, it was noted that the proportion of samples from old patients containing A. actinomycetemcomitans in combination with P. micra was almost three times higher than in samples when P. micra was replaced by P. gingivalis. In conclusion, A. actinomycetemcomitans showed an increased presence and proportion in samples from young patients compared with the old patients, while P. gingivalis was similarly distributed in the two age groups. P. micra showed an increased presence and proportion in samples from old patients compared with the young patients.
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| 50. |
- Claesson, Rolf, et al.
(författare)
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Carriage of the JP2 genotype of Aggregatibacter actinomycetemcomitans by periodontitis patients of various geographic origin, living in Sweden
- 2022
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Ingår i: Pathogens. - : MDPI. - 2076-0817. ; 11:11
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Tidskriftsartikel (refereegranskat)abstract
- The JP2 genotype of Aggregatibacter actinomycetemcomitans serotype b is associated with aggressive forms of periodontitis and was initially identified as affecting adolescents in North and West Africa. The dissemination of this genotype follows the migration routes and can today be detected in samples from periodontitis patients in a high number of countries. In the present study, we aim to describe findings of the JP2 genotype A. actinomycetemcomits in a clinical laboratory at the Dental School, Odontology, Umeå University, Sweden. The findings of JP2 carriers are documented during a 21-year period, and the age and geographic origin of the sampled individuals are described. In addition, the collected JP2 isolates were separated into North or West African origin by analyses of the presence of a point mutation in the hbpA2 pseudogene of the bacterium. In a total of 2296 sampled individuals during this period in this Swedish population of periodontitis patients, 32 JP2 carriers were detected by cultivation and PCR. The geographic background of these individuals was diverse, including sixteen with African origin, ten with a Swedish origin and six additional ones with a non-African origin. The JP2 genotypes of A. actinomycetemcomitans were mainly isolated from young individuals (<35 years of age), and seven out of the 32 isolates were of a West African origin based on the sequence of hbpA2. We conclude that the JP2 genotype of A. actinomycetemcomitans can be detected world-wide in subgingival plaque samples from adolescents affected by periodontitis.
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