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  • 51.
    Ahlstrom, Christina A. A.
    et al.
    US Geol Survey, AK 99508 USA.
    Woksepp, Hanna
    Kalmar Cty Reg, Sweden; Linnaeus Univ, Sweden.
    Sandegren, Linus
    Uppsala Univ, Sweden.
    Ramey, Andrew M. M.
    US Geol Survey, AK 99508 USA.
    Bonnedahl, Jonas
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för inflammation och infektion. Linköpings universitet, Medicinska fakulteten. Kalmar Cty Reg, Sweden.
    Exchange of Carbapenem-Resistant Escherichia coli Sequence Type 38 Intercontinentally and among Wild Bird, Human, and Environmental Niches2023Ingår i: Applied and Environmental Microbiology, ISSN 0099-2240, E-ISSN 1098-5336Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Carbapenem-resistant bacteria are a threat to public health globally and have been found in the environment as well as the clinic. Some bacterial clones are associated with carbapenem resistance genes, such as Escherichia coli sequence type 38 (ST38) and the carbapenemase gene bla(OXA-48). Carbapenem-resistant Enterobacteriaceae (CRE) are a global threat to human health and are increasingly being isolated from nonclinical settings. OXA-48-producing Escherichia coli sequence type 38 (ST38) is the most frequently reported CRE type in wild birds and has been detected in gulls or storks in North America, Europe, Asia, and Africa. The epidemiology and evolution of CRE in wildlife and human niches, however, remains unclear. We compared wild bird origin E. coli ST38 genome sequences generated by our research group and publicly available genomic data derived from other hosts and environments to (i) understand the frequency of intercontinental dispersal of E. coli ST38 clones isolated from wild birds, (ii) more thoroughly measure the genomic relatedness of carbapenem-resistant isolates from gulls sampled in Turkey and Alaska, USA, using long-read whole-genome sequencing and assess the spatial dissemination of this clone among different hosts, and (iii) determine whether ST38 isolates from humans, environmental water, and wild birds have different core or accessory genomes (e.g., antimicrobial resistance genes, virulence genes, plasmids) which might elucidate bacterial or gene exchange among niches. Our results suggest that E. coli ST38 strains, including those resistant to carbapenems, are exchanged between humans and wild birds, rather than separately maintained populations within each niche. Furthermore, despite close genetic similarity among OXA-48-producing E. coli ST38 clones from gulls in Alaska and Turkey, intercontinental dispersal of ST38 clones among wild birds is uncommon. Interventions to mitigate the dissemination of antimicrobial resistance throughout the environment (e.g., as exemplified by the acquisition of carbapenem resistance by birds) may be warranted.IMPORTANCE Carbapenem-resistant bacteria are a threat to public health globally and have been found in the environment as well as the clinic. Some bacterial clones are associated with carbapenem resistance genes, such as Escherichia coli sequence type 38 (ST38) and the carbapenemase gene bla(OXA-48). This is the most frequently reported carbapenem-resistant clone in wild birds, though it was unclear if it circulated within wild bird populations or was exchanged among other niches. The results from this study suggest that E. coli ST38 strains, including those resistant to carbapenems, are frequently exchanged among wild birds, humans, and the environment. Carbapenem-resistant E. coli ST38 clones in wild birds are likely acquired from the local environment and do not constitute an independent dissemination pathway within wild bird populations. Management actions aimed at preventing the environmental dissemination and acquisition of antimicrobial resistance by wild birds may be warranted.

  • 52.
    Ahlstrom, Christina A.
    et al.
    US Geol Survey, AK 99508 USA.
    Frick, Anna
    State Alaska Dept Hlth & Social Serv, AK USA.
    Pongratz, Catherine
    State Alaska Dept Hlth & Social Serv, AK USA.
    Spink, Kimberly
    State Alaska Dept Hlth & Social Serv, AK USA.
    Xavier, Catherine
    State Alaska Dept Hlth & Social Serv, AK USA.
    Bonnedahl, Jonas
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för inflammation och infektion. Linköpings universitet, Medicinska fakulteten. Kalmar Cty Council, Sweden.
    Ramey, Andrew M.
    US Geol Survey, AK 99508 USA.
    Genomic comparison of carbapenem-resistant Enterobacteriaceae from humans and gulls in Alaska2021Ingår i: Journal of Global Antimicrobial Resistance, ISSN 2213-7165, E-ISSN 2213-7173, Vol. 25, s. 23-25Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objectives: Wildlife may harbour clinically important antimicrobial-resistant bacteria, but the role of wildlife in the epidemiology of antimicrobial-resistant bacterial infections in humans is largely unknown. In this study, we aimed to assess dissemination of the bla(KPC) carbapenemase gene among humans and gulls in Alaska. Methods: We performed whole-genome sequencing to determine the genetic context of bla(KPC) in bacterial isolates from all four human carbapenemase-producing Enterobacteriaceae (CPE) infections reported in Alaska between 2013-2018 and to compare the sequences with seven previously reported CPE isolates from gull faeces within the same region and time period. Results: Genomic analysis of CPE isolates suggested independent acquisition events among humans with no evidence for direct transmission of bla(KPC) between people and gulls. However, some isolates shared conserved genetic elements surrounding bla(KPC), suggesting possible exchange between species. Conclusion: Our results highlight the genomic plasticity associated with bla(KPC) and demonstrate that sampling of wildlife may be useful for identifying clinically relevant antimicrobial resistance not observed through local passive surveillance in humans. Published by Elsevier Ltd on behalf of International Society for Antimicrobial Chemotherapy.

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  • 53.
    Ahlstrom, Christina A.
    et al.
    US Geol Survey, AK USA; US Geol Survey, AK 99508 USA.
    Scott, Laura C.
    US Geol Survey, AK USA.
    Woksepp, Hanna
    Reg Kalmar Cty, Sweden; Linnaeus Univ, Sweden.
    Bonnedahl, Jonas
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för inflammation och infektion. Linköpings universitet, Medicinska fakulteten. Reg Kalmar Cty, Sweden.
    Ramey, Andrew M.
    US Geol Survey, AK USA.
    Environmental antimicrobial resistance gene detection from wild bird habitats using two methods: A commercially available culture-independent qPCR assay and culture of indicator bacteria followed by whole-genome sequencing2023Ingår i: Journal of Global Antimicrobial Resistance, ISSN 2213-7165, E-ISSN 2213-7173, Vol. 33, s. 186-193Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objectives: A variety of methods have been developed to detect antimicrobial resistance (AMR) in differ-ent environments to better understand the evolution and dissemination of this public health threat. Com-parisons of results generated using different AMR detection methods, such as quantitative PCR (qPCR) and whole-genome sequencing (WGS), are often imperfect, and few studies have analysed samples in parallel to evaluate differences. In this study, we compared bacterial culture and WGS to a culture-independent commercially available qPCR assay to evaluate the concordance between methods and the utility of each in answering research questions regarding the presence and epidemiology of AMR in wild bird habitats.Methods: We first assessed AMR gene detection using qPCR in 45 bacterial isolates from which we had existing WGS data. We then analysed 52 wild bird faecal samples and 9 spatiotemporally collected water samples using culture-independent qPCR and WGS of phenotypically resistant indicator bacterial isolates.Results: Overall concordance was strong between qPCR and WGS of bacterial isolates, although concor-dance differed among antibiotic classes. Analysis of wild bird faecal and water samples revealed that more samples were determined to be positive for AMR via qPCR than via culture and WGS of bacterial isolates, although qPCR did not detect AMR genes in two samples from which phenotypically resistant isolates were found.Conclusions: Both qPCR and culture followed by sequencing may be effective approaches for characteris-ing AMR genes harboured by wild birds, although data streams produced using these different tools may have advantages and disadvantages that should be considered given the application and sample matrix.Published by Elsevier Ltd on behalf of International Society for Antimicrobial Chemotherapy. This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ )

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  • 54.
    Ahlstrom, Christina A.
    et al.
    US Geol Survey, AK 99508 USA.
    van Toor, Marielle L.
    Linnaeus Univ, Sweden.
    Woksepp, Hanna
    Kalmar Cty Hosp, Sweden.
    Chandler, Jeffrey C.
    USDA APHIS WS, CO 80521 USA.
    Reed, John A.
    US Geol Survey, AK 99508 USA.
    Reeves, Andrew B.
    US Geol Survey, AK 99508 USA.
    Waldenstrom, Jonas
    Linnaeus Univ, Sweden.
    Franklin, Alan B.
    USDA APHIS WS, CO 80521 USA.
    Douglas, David C.
    US Geol Survey, AK 99801 USA.
    Bonnedahl, Jonas
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för inflammation och infektion. Linköpings universitet, Medicinska fakulteten. Dept Infect Dis, Sweden.
    Ramey, Andrew M.
    US Geol Survey, AK 99508 USA.
    Evidence for continental-scale dispersal of antimicrobial resistant bacteria by landfill-foraging gulls2021Ingår i: Science of the Total Environment, ISSN 0048-9697, E-ISSN 1879-1026, Vol. 764, artikel-id 144551Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Anthropogenic inputs into the environment may serve as sources of antimicrobial resistant bacteria and alter the ecology and population dynamics of synanthropic wild animals by providing supplemental forage. In this study, we used a combination of phenotypic and genomic approaches to characterize antimicrobial resistant indicator bacteria, animal telemetry to describe host movement patterns, and a novel modeling approach to combine information from these diverse data streams to investigate the acquisition and long-distance dispersal of antimicrobial resistant bacteria by landfill-foraging gulls. Our results provide evidence that gulls acquire antimicrobial resistant bacteria from anthropogenic sources, which they may subsequently disperse across and between continents via migratory movements. Furthermore, we introduce a flexible modeling framework to estimate the relative dispersal risk of antimicrobial resistant bacteria in western North America and adjacent areas within East Asia, which may be adapted to provide information on the risk of dissemination of other organisms and pathogens maintained by wildlife through space and time. Published by Elsevier B.V.

  • 55.
    Ahlstrom, Christina A.
    et al.
    US Geol Survey, AK 99508 USA.
    Woksepp, Hanna
    Kalmar Cty Hosp, Sweden; Linnaeus Univ, Sweden.
    Sandegren, Linus
    Uppsala Univ, Sweden.
    Mohsin, Mashkoor
    Univ Agr Faisalabad, Pakistan.
    Hasan, Badrul
    Uppsala Univ, Sweden; Anim Bacteriol Sect, Australia.
    Muzyka, Denys
    Inst Expt & Clin Vet Med, Ukraine.
    Hernandez, Jorge
    Kalmar Cty Hosp, Sweden.
    Aguirre, Filip
    Kalmar Cty Hosp, Sweden.
    Tok, Atalay
    Uppsala Univ, Sweden.
    Söderman, Jan
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Olsen, Bjorn
    Uppsala Univ, Sweden.
    Ramey, Andrew M.
    US Geol Survey, AK 99508 USA.
    Bonnedahl, Jonas
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för inflammation och infektion. Linköpings universitet, Medicinska fakulteten. Region Kalmar Cty, Sweden.
    Genomically diverse carbapenem resistant Enterobacteriaceae from wild birds provide insight into global patterns of spatiotemporal dissemination2022Ingår i: Science of the Total Environment, ISSN 0048-9697, E-ISSN 1879-1026, Vol. 824, artikel-id 153632Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Carbapenem resistant Enterobacteriaceae (CRE) are a threat to public health globally, yet the role of the environment in the epidemiology of CRE remains elusive. Given that wild birds can acquire CRE, likely from foraging in anthropogenically impacted areas, and may aid in the maintenance and dissemination of CRE in the environment, a spatiotemporal comparison of isolates from different regions and timepoints may be useful for elucidating epidemiological information. Thus, we characterized the genomic diversity of CRE from fecal samples opportunistically collected from gulls (Larus spp.) inhabiting Alaska (USA), Chile, Spain, Turkey, and Ukraine and from black kites (Milvus migrans) sampled in Pakistan and assessed evidence for spatiotemporal patterns of dissemination. Within and among sampling locations, a high diversity of carbapenemases was found, including Klebsiella pneumoniae carbapenemase (KPC), New Delhi metallo-beta-lactamase (NDM), oxacillinase (OXA), and Verona integron Metallo beta-lactamase (VIM). Although the majority of genomic comparisons among samples did not provide evidence for spatial dissemination, we did find strong evidence for dissemination among Alaska, Spain, and Turkey. We also found strong evidence for temporal dissemination among samples collected in Alaska and Pakistan, though the majority of CRE clones were transitory and were not repeatedly detected among locations where samples were collected longitudinally. Carbapenemase-producing hypervirulent K. pneumoniae was isolated from gulls in Spain and Ukraine and some isolates harbored antimicrobial resistance genes conferring resistance to up to 10 different antibiotic classes, including colistin. Our results are consistent with local acquisition of CRE by wild birds with spatial dissemination influenced by intermediary transmission routes, likely involving humans. Furthermore, our results support the premise that anthropogenicallyassociated wild birds may be good sentinels for understanding the burden of clinically-relevant antimicrobial resistance in the local human population.

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  • 56.
    Ahlström, Stina
    et al.
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för klinisk kemi och farmakologi. Linköpings universitet, Medicinska fakulteten. Natl Board Forens Med, Sweden.
    Ahlner, Johan
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för klinisk kemi och farmakologi. Linköpings universitet, Medicinska fakulteten.
    Jönsson, Anna K
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för klinisk kemi och farmakologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk farmakologi. Natl Board Forens Med, Dept Forens Genet & Forens Toxicol, S-58758 Linkoping, Sweden.
    Green, Henrik
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för klinisk kemi och farmakologi. Linköpings universitet, Medicinska fakulteten. Natl Board Forens Med, Dept Forens Genet & Forens Toxicol, S-58758 Linkoping, Sweden.
    The Importance of BHB Testing on the Post-Mortem Diagnosis of Ketoacidosis2022Ingår i: Biomolecules, E-ISSN 2218-273X, Vol. 12, nr 1, artikel-id 9Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Although beta-hydroxybutyrate (BHB) analysis has proved its importance in forensic pathology, its effects on cause-of-death diagnostics are unaddressed. Therefore, this study aims at evaluating the effects of BHB analysis on the number of deaths by DKA (diabetes ketoacidosis), AKA (alcoholic ketoacidosis), HHS (hyperosmolar hyperglycaemic state), hypothermia, diabetes, alcoholism, and acidosis NOS (not otherwise specified). All 2900 deaths from 2013 through 2019 in which BHB was analysed at the National Board of Forensic Medicine, and 1069 DKA, AKA, HHS, hypothermia, diabetes, alcoholism, and acidosis cases without BHB analysis were included. The prevalence of BHB-positive cases for each cause of death, and trends and proportions of different BHB concentrations, were investigated. The number of BHB analyses/year increased from 13 to 1417. AKA increased from three to 66 and acidosis from one to 20. The deaths from alcoholism, DKA, and hypothermia remained stable. It is unclear why death from alcoholism remained stable while AKA increased. The increase in unspecific acidosis deaths raises the question why a more specific diagnosis had not been used. In conclusion, BHB analysis is instrumental in detecting AKA and acidosis. The scientific basis for the diagnosis of DKA and hypothermia improved, but the number of cases did not change.

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  • 57.
    Ahlström, Stina
    et al.
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för klinisk kemi och farmakologi. Linköpings universitet, Medicinska fakulteten. Natl Board Forens Med, Sweden.
    Thiblin, Ingemar
    Natl Board Forens Med, Sweden; Uppsala Univ, Sweden.
    Jönsson, Anna K
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för klinisk kemi och farmakologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk farmakologi. Natl Board Forens Med, Dept Forens Genet & Forens Toxicol, Linkoping, Sweden.
    Green, Henrik
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för klinisk kemi och farmakologi. Linköpings universitet, Medicinska fakulteten. Natl Board Forens Med, Dept Forens Genet & Forens Toxicol, Linkoping, Sweden.
    Characteristics of post-mortem beta-hydroxybutyrate-positivet cases - A retrospective study on age, sex and BMI in 1407 forensic autopsies2021Ingår i: Forensic Science International, ISSN 0379-0738, E-ISSN 1872-6283, Vol. 325, artikel-id 110878Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Post-mortem biochemistry, including the analysis of beta-hydroxybutyrate (BHB), is increasingly employed in forensic medicine, especially in conditions such as diabetes and chronic alcoholism. However, not much is known about the associations between age, body mass index (BMI), and sex and BHB concentrations in ketoacidotic conditions. Aim: To retrospectively study the association between age, BMI and sex in several conditions, such as diabetic ketoacidosis (DKA), alcoholic ketoacidosis (AKA), and elevated post-mortem BHB concentrations. Methods: 1407 forensic autopsy cases analysed for BHB were grouped by diagnosis: DKA, AKA, HHS [hyperosmolar hyperglycaemic state], acidosis NOS [not otherwise specified], or hypothermia. Age, sex, BMI and the concentrations of blood alcohol, vitreous glucose and blood BHB were recorded. Results: Cases of AKA and DKA were most numerous (184 and 156, respectively). In DKA and in its male subgroup, cases with severe ketosis (BHB > 1000 mu g/g) were younger and had a lower BMI than those with moderate ketosis (BHB 250-1000 mu g/g) and controls (P < 0.001). In DKA and in its female subgroup, cases with moderate ketosis cases were older (P = 0.0218 and P = 0.0083) than controls. In AKA and in its male subgroup, cases with severe ketosis had a lower BMI than those with moderate ketosis (P = 0.0391 and P = 0.0469) and controls (P < 0.001). Cases with moderate ketosis had a lower BMI than controls (P < 0.001). Conclusions: BHB concentration is associated with BMI in DKA and AKA, and with both BMI and age in DKA. Constitutional factors should, therefore, be considered in potential AKA and DKA cases. (c) 2021 The Authors. Published by Elsevier B.V. CC_BY_4.0

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  • 58. Beställ onlineKöp publikationen >>
    Ahmad, Awais
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för inflammation och infektion. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk immunologi och transfusionsmedicin.
    Autoantibodies in healthy blood donors, rheumatic and autoimmune liver diseases2024Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [sv]

    Autoimmunitet är ett vanligt fenomen där immunsystemet känner igen kroppens egna vävnader. Autoimmunitet kan leda till sjukdom om vävnadsskada uppstår. Autoimmuna sjukdomar drabbar 5–10 % av den globala befolkningen och vid många av dessa kan autoantikroppar påvisas. Autoantikropparna kan detekteras med flera olika metoder. I denna avhandling användes line immunoassay och fluorescensenzym immunoassay för att undersöka förekomsten av autoantikroppar hos blodgivare och olika sjukdomsgrupper. Line immunoassay använder sig av remsor medan fluorescensenzym immunoassay använder sig av brunnar. Remsorna och brunnarna är täckta med proteiner som får reagera med serumprov från patienten. Vid förekomst av autoantikroppar sker antingen ett färgomslag (line immunoassay) eller ljusreaktion (fluorescensenzym immunoassay).

    Studie I och II: Med EuroLine -Autoimmune Liver Diseases- (IgG) line immunoassay analyserades förekomsten av autoantikroppar associerade med autoimmuna leversjukdomar hos blodgivare, patienter med autoimmuna leversjukdomar samt SLE patienter. Autoantikroppar detekterades hos flera blodgivare. En sällsynt autoantikropp, anti-LC-1, var vanligare hos blodgivare än hos patienter med autoimmuna leversjukdomar. Trots förekomsten av autoantikroppar sågs inget samband med avvikande levervärden hos blodgivare eller SLE patienter. Genom att höja referensvärden minskade antalet "falskt positiva" resultat. Dock kunde detta inte åtgärda problemet med anti-LC-1, vilket indikerar problem med LC-1-antigenet där ospecifika reaktioner detekteras. Risken för att utveckla autoimmun leversjukdom bedömdes vara låg hos SLE-patienterna, då ingen av dessa utvecklade autoimmun leversjukdom trots flera års uppföljning. Majoriteten av de positiva fynden med EuroLine immunoassay kunde inte bekräftas med andra metoder, vilket talar för att denna metod är mycket känslig.

    Studie III: Med EuroLine Systemic Sclerosis (Nucleoli) Profile (IgG) line immunoassay kunde de sällsynta autoantikropparna anti-Th/To och anti-NOR90 påvisas lika ofta hos blodgivare som hos patienter med systemisk skleros. Majoriteten av de andra autoantikropparna var vanligare hos patienter med systemisk skleros jämfört med blodgivare och andra sjukdomsgrupper. Vissa autoantikroppar var associerade med specifika kliniska manifestationer, däribland njurpåverkan hos SLE patienter. Dessa fynd behöver verifieras.

    Studie IV: Autoantikroppar som binder U1-RNP proteinet (anti-U1-RNP) kan påvisas hos SLE patienter. Patienter med anti-U1-RNP kan analyseras vidare för förekomst av autoantikroppar mot proteinet RNP 70kDa (anti-RNP70), men det kliniska värdet av detta är osäkert. I denna studie användes fluorescensenzym immunoassay för analys av anti-U1- RNP positiva prover avseende anti-RNP70 för att utvärdera om det tillförde något av kliniskt värde vid SLE. Förekomst av anti-U1-RNP var associerat med lågt antal av vita blodkroppar och mindre organskada. Analys av anti-RNP70 tillförde dock inte någon ytterligare klinisk information.

    Slutsats: Euroline -Autoimmune Liver Diseases- (IgG) och EuroLine Systemic Sclerosis (Nucleoli) Profile (IgG) är verktyg som är av värde vid diagnostik av autoimmuna leversjukdomar och systemisk skleros, men metoderna har hög känslighet vilket kan leda till falskt positiva resultat. Genom att höja referensvärden kan man minska risken för detta. Några sällsynta antikroppar hittades oftare hos blodgivare än hos patienter med de olika sjukdomsgrupperna, vilket antyder potentiella problem med antigenkällan. Subtypning av anti-RNP70 hos SLE patienter med anti-U1-RNP tillförde inte något av kliniskt värde.

    Delarbeten
    1. Autoantibodies associated with primary biliary cholangitis are common among patients with systemic lupus erythematosus even in the absence of elevated liver enzymes
    Öppna denna publikation i ny flik eller fönster >>Autoantibodies associated with primary biliary cholangitis are common among patients with systemic lupus erythematosus even in the absence of elevated liver enzymes
    Visa övriga...
    2021 (Engelska)Ingår i: Clinical and Experimental Immunology, ISSN 0009-9104, E-ISSN 1365-2249, Vol. 203, nr 1, s. 22-31Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Knowledge of concomitant autoimmune liver diseases (AILD) is more detailed in primary Sjogrens syndrome (pSS) compared to systemic lupus erythematosus (SLE). Herein, the prevalence of autoantibodies associated with autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC) was investigated in stored sera from patients with SLE (n = 280) and pSS (n = 114). Antibodies against mitochondria (AMA), liver-kidney microsomal (LKM) antigen, smooth muscle (SMA) and anti-nuclear antibodies (ANA) were analysed with immunofluorescence microscopy. In addition, AILD-associated autoantibodies were tested with immunoblot. Prior to sampling, eight SLE (2 center dot 9%) and three pSS (2 center dot 6%) cases were diagnosed with AILD. Among SLE-cases without known AILD (n = 272), 26 (9 center dot 6%) had PBC-associated autoantibodies, 15 (5 center dot 5%) AIH-associated autoantibodies (excluding ANA) and one serological overlap. Most subjects with PBC-associated autoantibodies had liver enzymes within reference limits (22 of 27, 81%) or mild laboratory cholestasis (two of 27, 7 center dot 4%), while one fulfilled the diagnostic PBC-criteria. AMA-M2 detected by immunoblot was the most common PBC-associated autoantibody in SLE (20 of 272, 7 center dot 4%). The prevalence of SMA (4 center dot 4%) was comparable with a healthy reference population, but associated with elevated liver enzymes in four of 12 (25%), none meeting AIH-criteria. The patient with combined AIH/PBC-serology had liver enzymes within reference limits. Among pSS cases without known AILD (n = 111), nine (8 center dot 1%) had PBC-associated, 12 (10 center dot 8%) AIH-associated autoantibodies and two overlapped. PBC-associated autoantibodies were found as frequently in SLE as in pSS but were, with few exceptions, not associated with laboratory signs of liver disease. Overall, AILD-associated autoantibodies were predominantly detected by immunoblot and no significant difference in liver enzymes was found between AILD autoantibody-negative and -positive patients.

    Ort, förlag, år, upplaga, sidor
    Wiley-Blackwell Publishing Inc., 2021
    Nyckelord
    autoantibodies; autoimmune hepatitis; primary biliary cholangitis; Sjogrens syndrome; systemic lupus erythematosus
    Nationell ämneskategori
    Gastroenterologi
    Identifikatorer
    urn:nbn:se:liu:diva-170539 (URN)10.1111/cei.13512 (DOI)000573490000001 ()32910463 (PubMedID)2-s2.0-85091690857 (Scopus ID)
    Anmärkning

    Funding Agencies|Swedish Rheumatism Association; Region ostergotland (ALF grants); Swedish Society of Medicine; King Gustaf Vs 80-year Anniversary foundation; King Gustaf V and Queen Victorias Freemasons foundation

    Tillgänglig från: 2020-10-16 Skapad: 2020-10-16 Senast uppdaterad: 2024-02-05Bibliografiskt granskad
    2. Autoantibodies Associated with Autoimmune Liver Diseases in a Healthy Population: Evaluation of a Commercial Immunoblot Test
    Öppna denna publikation i ny flik eller fönster >>Autoantibodies Associated with Autoimmune Liver Diseases in a Healthy Population: Evaluation of a Commercial Immunoblot Test
    Visa övriga...
    2022 (Engelska)Ingår i: Diagnostics, ISSN 2075-4418, Vol. 12, nr 7, artikel-id 1572Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Autoantibodies constitute important tools for diagnosing the autoimmune liver diseases (AILD) autoimmune hepatitis and primary biliary cholangitis. The EUROLINE immunoblot assay, detecting multiple specificities, is widely used, but the clinical importance of weakly positive findings is unclear. The manufacturers recommended cut-off was evaluated by investigating AILD-associated autoantibodies in 825 blood donors and 60 confirmed AILD cases. Positive findings were followed up with immunofluorescence microscopy on rat tissue, anti-M2-ELISA, alternative immunoblot assay, and liver function tests. Thirty-six (4.4%) blood donors were positive with EUROLINE. The most common specificities were LC-1 (1.6%), gp210 (1.3%), and AMA-M2 (1.1%). In general, the positive results were higher in patients than in blood donors, whereas anti-LC-1 was higher in blood donors. The liver function tests were slightly elevated in 2 of the 36 immunoblot positive blood donors. The majority of the positive EUROLINE findings could not be confirmed with the follow-up tests. The EUROLINE-Autoimmune Liver Diseases-(IgG) immunoblot detected autoantibodies in 4.4% of blood donors without signs of AILD. Our findings indicate that the recommended cut-off can be raised for most specificities without loss of diagnostic sensitivity. The prevalence of anti-LC-1 among blood donors indicates a problem with the antigen source.

    Ort, förlag, år, upplaga, sidor
    MDPI, 2022
    Nyckelord
    autoimmune liver disease; AIH; PBC; PML; Sp100; gp210; AMA-M2; EUROLINE
    Nationell ämneskategori
    Radiologi och bildbehandling
    Identifikatorer
    urn:nbn:se:liu:diva-187446 (URN)10.3390/diagnostics12071572 (DOI)000831404600001 ()35885478 (PubMedID)
    Anmärkning

    Funding Agencies|Region Ostergotland (ALF grants) [RO932055]

    Tillgänglig från: 2022-08-23 Skapad: 2022-08-23 Senast uppdaterad: 2024-02-05
    3. Autoantibodies associated with systemic sclerosis in three autoimmune diseases imprinted by type I interferon gene dysregulation: a comparison across SLE, primary Sjogrens syndrome and systemic sclerosis
    Öppna denna publikation i ny flik eller fönster >>Autoantibodies associated with systemic sclerosis in three autoimmune diseases imprinted by type I interferon gene dysregulation: a comparison across SLE, primary Sjogrens syndrome and systemic sclerosis
    Visa övriga...
    2022 (Engelska)Ingår i: Lupus Science and Medicine, E-ISSN 2053-8790, Vol. 9, nr 1, artikel-id e000732Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    ObjectiveSLE, primary Sjogrens syndrome (pSS) and systemic sclerosis (SSc) are heterogeneous autoimmune diseases with a dysregulated type I interferon (IFN) system. The diseases often show overlapping clinical manifestations, which may result in diagnostic challenges. We asked to which extent SSc-associated autoantibodies are present in SLE and pSS, and whether these link to serum IFN-alpha, clinical phenotypes and sex. Samples with clinical data from patients with SSc and healthy blood donors (HBDs) served as controls. Finally, the diagnostic performance of SSc-associated autoantibodies was evaluated.MethodsSamples from well-characterised subjects with SLE (n=510), pSS (n=116), SSc (n=57) and HBDs (n=236) were analysed using a commercially available immunoassay (EuroLine Systemic Sclerosis Profile (IgG)). IFN-alpha was quantified by ELISA. Self-reported data on Raynauds phenomenon (RP) were available.ResultsWith exceptions for anti-Ro52/SSA and anti-Th/To, SSc-associated autoantibodies were more frequent in SSc than in SLE, pSS and HBDs regardless of sex. IFN-alpha levels correlated with the number of positive SSc-associated autoantibodies (r=0.29, p<0.0001) and associated with Ro52/SSA positivity (p<0.0001). By using data from SLE, SSc and HBDs, RP was significantly associated with topoisomerase I, centromere protein (CENP)-B, RNA polymerase III 11 kDa, RNA polymerase III 155 kDa and PM-Scl100 whereas Ro52/SSA associated inversely with RP. In SLE, CENP-A was associated with immunological disorder, CENP-B with serositis and Ku with lupus nephritis. By combining analysis of ANA (immunofluorescence) with SSc-associated autoantibodies, the diagnostic sensitivity reached 98% and the specificity 33%.ConclusionsThe 13 specificities included in the EuroLine immunoassay are commonly detected in SSc, but they are also frequent among individuals with other diseases imprinted by type I IFNs. These findings are valuable when interpreting serological data on patients with suspected SSc, especially as patients may present with disease manifestations overlapping different rheumatological diseases. In SLE, we observed associations between manifestations and SSc-associated autoantibodies which have not previously been reported.

    Ort, förlag, år, upplaga, sidor
    BMJ PUBLISHING GROUP, 2022
    Nyckelord
    Sjogrens Syndrome; Scleroderma; Systemic; Lupus Erythematosus; Interferon Type I; Autoantibodies
    Nationell ämneskategori
    Reumatologi och inflammation
    Identifikatorer
    urn:nbn:se:liu:diva-191220 (URN)10.1136/lupus-2022-000732 (DOI)000906026900002 ()36581379 (PubMedID)
    Anmärkning

    Funding Agencies|King Gustaf V and Queen Victorias Freemasons Foundation; King Gustaf Vs 80-year Anniversary Foundation; Gustafsson Foundation; Swedish Rheumatism Association, Region OEstergoetland (ALF grants)

    Tillgänglig från: 2023-01-23 Skapad: 2023-01-23 Senast uppdaterad: 2024-02-05
    4. Doubtful Clinical Value of Subtyping Anti-U1-RNP Antibodies Regarding the RNP-70 kDa Antigen in Sera of Patients with Systemic Lupus Erythematosus
    Öppna denna publikation i ny flik eller fönster >>Doubtful Clinical Value of Subtyping Anti-U1-RNP Antibodies Regarding the RNP-70 kDa Antigen in Sera of Patients with Systemic Lupus Erythematosus
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    2023 (Engelska)Ingår i: International Journal of Molecular Sciences, ISSN 1661-6596, E-ISSN 1422-0067, Vol. 24, nr 12, artikel-id 10398Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    The detection of antinuclear antibodies is central to the diagnosis and prognosis of systemic lupus erythematosus (SLE), primary Sjogrens syndrome (pSS) and mixed connective tissue disease (MCTD). Anti-U1-RNP and anti-RNP70 antibodies were assayed in the sera of patients with SLE (n = 114), pSS (n = 54) and MCTD (n = 12). In the SLE group, 34/114 (30%) were anti-U1-RNP positive, and 21/114 (18%) were both anti-RNP70 positive and anti-U1-RNP positive. In the MCTD group, 10/12 (83%) were anti-U1-RNP positive, and 9/12 (75%) were anti-RNP70 positive. Only one individual with pSS was antibody positive (for both anti-U1-RNP and anti-RNP70). All anti-RNP70-positive samples were also anti-U1-RNP positive. Anti-U1-RNP-positive subjects with SLE were younger (p < 0.0001); showed lower concentrations of complement protein 3 (p = 0.03); had lower eosinophil (p = 0.0005), lymphocyte (p = 0.006) and monocyte (p = 0.03) counts; and had accrued less organ damage (p = 0.006) than the anti-U1-RNP-negative SLE patients. However, we observed no significant clinical or laboratory parameter differences between the anti-U1-RNP-positive individuals with/without anti-RNP70 in the SLE group. In conclusion, anti-RNP70 antibodies are not exclusive to MCTD but are rarely detected in pSS and healthy individuals. In SLE, anti-U1-RNP antibodies are associated with a clinical phenotype that resembles MCTD, with hematologic involvement and less damage accrual. Based on our results, the clinical value of subtyping anti-RNP70 in anti-U1-RNP-positive sera appears to be of limited value.

    Ort, förlag, år, upplaga, sidor
    MDPI, 2023
    Nyckelord
    autoantibodies; mixed connective tissue disease; primary Sjogrens syndrome; small nuclear ribonucleoprotein antibodies; systemic lupus erythematosus
    Nationell ämneskategori
    Odontologi
    Identifikatorer
    urn:nbn:se:liu:diva-196857 (URN)10.3390/ijms241210398 (DOI)001014922500001 ()37373545 (PubMedID)
    Tillgänglig från: 2023-08-24 Skapad: 2023-08-24 Senast uppdaterad: 2024-02-05
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  • 59.
    Ahmad, Awais
    et al.
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för inflammation och infektion. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk immunologi och transfusionsmedicin.
    Brylid, Andre
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för inflammation och infektion. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk immunologi och transfusionsmedicin.
    Dahle, Charlotte
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för inflammation och infektion. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk immunologi och transfusionsmedicin.
    Saleh, Muna Atallah
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för inflammation och infektion. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Medicincentrum, Reumatologiska kliniken i Östergötland.
    Dahlström, Örjan
    Linköpings universitet, Institutionen för beteendevetenskap och lärande, Psykologi. Linköpings universitet, Filosofiska fakulteten. Linköpings universitet, Institutet för handikappvetenskap (IHV).
    Enocsson, Helena
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för inflammation och infektion. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Medicincentrum, Reumatologiska kliniken i Östergötland.
    Sjöwall, Christopher
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för inflammation och infektion. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Medicincentrum, Reumatologiska kliniken i Östergötland.
    Doubtful Clinical Value of Subtyping Anti-U1-RNP Antibodies Regarding the RNP-70 kDa Antigen in Sera of Patients with Systemic Lupus Erythematosus2023Ingår i: International Journal of Molecular Sciences, ISSN 1661-6596, E-ISSN 1422-0067, Vol. 24, nr 12, artikel-id 10398Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The detection of antinuclear antibodies is central to the diagnosis and prognosis of systemic lupus erythematosus (SLE), primary Sjogrens syndrome (pSS) and mixed connective tissue disease (MCTD). Anti-U1-RNP and anti-RNP70 antibodies were assayed in the sera of patients with SLE (n = 114), pSS (n = 54) and MCTD (n = 12). In the SLE group, 34/114 (30%) were anti-U1-RNP positive, and 21/114 (18%) were both anti-RNP70 positive and anti-U1-RNP positive. In the MCTD group, 10/12 (83%) were anti-U1-RNP positive, and 9/12 (75%) were anti-RNP70 positive. Only one individual with pSS was antibody positive (for both anti-U1-RNP and anti-RNP70). All anti-RNP70-positive samples were also anti-U1-RNP positive. Anti-U1-RNP-positive subjects with SLE were younger (p < 0.0001); showed lower concentrations of complement protein 3 (p = 0.03); had lower eosinophil (p = 0.0005), lymphocyte (p = 0.006) and monocyte (p = 0.03) counts; and had accrued less organ damage (p = 0.006) than the anti-U1-RNP-negative SLE patients. However, we observed no significant clinical or laboratory parameter differences between the anti-U1-RNP-positive individuals with/without anti-RNP70 in the SLE group. In conclusion, anti-RNP70 antibodies are not exclusive to MCTD but are rarely detected in pSS and healthy individuals. In SLE, anti-U1-RNP antibodies are associated with a clinical phenotype that resembles MCTD, with hematologic involvement and less damage accrual. Based on our results, the clinical value of subtyping anti-RNP70 in anti-U1-RNP-positive sera appears to be of limited value.

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  • 60.
    Ahmad, Awais
    et al.
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för inflammation och infektion. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk immunologi och transfusionsmedicin.
    Dahle, Charlotte
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för inflammation och infektion. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk immunologi och transfusionsmedicin.
    Rönnelid, Johan
    Uppsala Univ, Sweden.
    Sjöwall, Christopher
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för inflammation och infektion. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Medicincentrum, Reumatologiska kliniken i Östergötland.
    Kechagias, Stergios
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för diagnostik och specialistmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Mag- tarmmedicinska kliniken.
    Autoantibodies Associated with Autoimmune Liver Diseases in a Healthy Population: Evaluation of a Commercial Immunoblot Test2022Ingår i: Diagnostics, ISSN 2075-4418, Vol. 12, nr 7, artikel-id 1572Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Autoantibodies constitute important tools for diagnosing the autoimmune liver diseases (AILD) autoimmune hepatitis and primary biliary cholangitis. The EUROLINE immunoblot assay, detecting multiple specificities, is widely used, but the clinical importance of weakly positive findings is unclear. The manufacturers recommended cut-off was evaluated by investigating AILD-associated autoantibodies in 825 blood donors and 60 confirmed AILD cases. Positive findings were followed up with immunofluorescence microscopy on rat tissue, anti-M2-ELISA, alternative immunoblot assay, and liver function tests. Thirty-six (4.4%) blood donors were positive with EUROLINE. The most common specificities were LC-1 (1.6%), gp210 (1.3%), and AMA-M2 (1.1%). In general, the positive results were higher in patients than in blood donors, whereas anti-LC-1 was higher in blood donors. The liver function tests were slightly elevated in 2 of the 36 immunoblot positive blood donors. The majority of the positive EUROLINE findings could not be confirmed with the follow-up tests. The EUROLINE-Autoimmune Liver Diseases-(IgG) immunoblot detected autoantibodies in 4.4% of blood donors without signs of AILD. Our findings indicate that the recommended cut-off can be raised for most specificities without loss of diagnostic sensitivity. The prevalence of anti-LC-1 among blood donors indicates a problem with the antigen source.

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  • 61.
    Ahmad, Awais
    et al.
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för inflammation och infektion. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk immunologi och transfusionsmedicin.
    Heijke, R.
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för inflammation och infektion. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Medicincentrum, Reumatologiska kliniken i Östergötland.
    Eriksson, Per
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för inflammation och infektion. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Medicincentrum, Reumatologiska kliniken i Östergötland.
    Wirestam, Lina
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för inflammation och infektion. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Medicincentrum, Reumatologiska kliniken i Östergötland.
    Kechagias, Stergios
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för diagnostik och specialistmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Mag- tarmmedicinska kliniken.
    Dahle, Charlotte
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för inflammation och infektion. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk immunologi och transfusionsmedicin.
    Sjöwall, Christopher
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för inflammation och infektion. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Medicincentrum, Reumatologiska kliniken i Östergötland.
    Autoantibodies associated with primary biliary cholangitis are common among patients with systemic lupus erythematosus even in the absence of elevated liver enzymes2021Ingår i: Clinical and Experimental Immunology, ISSN 0009-9104, E-ISSN 1365-2249, Vol. 203, nr 1, s. 22-31Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Knowledge of concomitant autoimmune liver diseases (AILD) is more detailed in primary Sjogrens syndrome (pSS) compared to systemic lupus erythematosus (SLE). Herein, the prevalence of autoantibodies associated with autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC) was investigated in stored sera from patients with SLE (n = 280) and pSS (n = 114). Antibodies against mitochondria (AMA), liver-kidney microsomal (LKM) antigen, smooth muscle (SMA) and anti-nuclear antibodies (ANA) were analysed with immunofluorescence microscopy. In addition, AILD-associated autoantibodies were tested with immunoblot. Prior to sampling, eight SLE (2 center dot 9%) and three pSS (2 center dot 6%) cases were diagnosed with AILD. Among SLE-cases without known AILD (n = 272), 26 (9 center dot 6%) had PBC-associated autoantibodies, 15 (5 center dot 5%) AIH-associated autoantibodies (excluding ANA) and one serological overlap. Most subjects with PBC-associated autoantibodies had liver enzymes within reference limits (22 of 27, 81%) or mild laboratory cholestasis (two of 27, 7 center dot 4%), while one fulfilled the diagnostic PBC-criteria. AMA-M2 detected by immunoblot was the most common PBC-associated autoantibody in SLE (20 of 272, 7 center dot 4%). The prevalence of SMA (4 center dot 4%) was comparable with a healthy reference population, but associated with elevated liver enzymes in four of 12 (25%), none meeting AIH-criteria. The patient with combined AIH/PBC-serology had liver enzymes within reference limits. Among pSS cases without known AILD (n = 111), nine (8 center dot 1%) had PBC-associated, 12 (10 center dot 8%) AIH-associated autoantibodies and two overlapped. PBC-associated autoantibodies were found as frequently in SLE as in pSS but were, with few exceptions, not associated with laboratory signs of liver disease. Overall, AILD-associated autoantibodies were predominantly detected by immunoblot and no significant difference in liver enzymes was found between AILD autoantibody-negative and -positive patients.

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  • 62.
    Ahmad, Irma
    et al.
    Orebro Univ, Sweden.
    Sandberg, Matilda
    Orebro Univ, Sweden.
    Brus, Ole
    Orebro Univ, Sweden.
    Ekman, Carl Johan
    Karolinska Inst, Sweden.
    Hammar, Åsa
    Univ Bergen, Norway.
    Landén, Mikael
    Karolinska Institutet, Stockholm, Sweden; The Sahlgrenska Academy at Gothenburg University, Gothenburg, Sweden.
    Lundberg, Johan
    Karolinska Inst, Sweden; Stockholm Health Care Services, Stockholm, Sweden.
    Nordanskog, Pia
    Linköpings universitet, Medicinska fakulteten. Region Östergötland, Psykiatricentrum, Psykiatriska kliniken i Linköping. Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Centrum för social och affektiv neurovetenskap.
    von Knorring, Lars
    Uppsala University, Uppsala, Sweden.
    Nordenskjöld, Axel
    Örebro University, Örebro, Sweden.
    Validity of diagnoses, treatment dates, and rating scales in the Swedish national quality register for electroconvulsive therapy2022Ingår i: Nordic Journal of Psychiatry, ISSN 0803-9488, E-ISSN 1502-4725, Vol. 76, nr 2, s. 96-103Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background The Swedish national quality register for electroconvulsive therapy (Q-ECT) contains data on patients receiving treatment with electroconvulsive therapy (ECT) in Sweden. Aim This study determined the validity of diagnoses, treatment dates, and rating scales in the Q-ECT by investigating the degree of accordance between data from the Q-ECT and patient records. Materials and methods From January 2016 to December 2017, 200 treatment series were randomly selected from the Q-ECT. The corresponding patient records were requested from the treating hospitals. Data on the indicative diagnosis, dates for the first and the last ECT session, and rating scales were compared between the Q-ECT and patient records using (i) a strict and (ii) a liberal method of assessment. Using the liberal method, each variable was assessed as accordant if it belonged to the same diagnosis group, or if the dates differed by less than 1 week, or ratings differed by only 1 point on the Clinical Global Impression Scale (CGI- S), or no more than 3 points on the Montgomery angstrom sberg Depression Rating Scale between the Q-ECT and the patient record. Results A total of 179 patient records were received. The strict method of assessment showed an accordance of 89% or higher for all studied variables. The liberal method showed an accordance of 95% or higher. Conclusions We conclude that data on the studied variables in the Q-ECT have high validity. However, limited use of some rating scales makes the results uncertain. Measures can be taken to further improve the data quality.

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  • 63.
    Ahmadi, Shilan Seyed
    et al.
    Univ Gothenburg, Sweden; Sahlgrens Univ Hosp, Sweden; Uddevalla Cent Hosp, Sweden.
    Pivodic, Aldina
    Stat Konsultgrp, Sweden; Univ Gothenburg, Sweden.
    Svensson, Ann-Marie
    Ctr Registers Reg Vastra Gotaland, Sweden.
    Wedel, Hans
    Univ Gothenburg, Sweden.
    Rathsman, Björn
    Sachs Children & Youth Hosp, Sweden.
    Nyström, Thomas
    Karolinska Inst, Sweden.
    Ludvigsson, Johnny
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Barn- och kvinnocentrum, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Lind, Marcus
    Univ Gothenburg, Sweden; Sahlgrens Univ Hosp, Sweden; NU Hosp Grp, Sweden.
    Risk factors for nephropathy in persons with type 1 diabetes: a population-based study2022Ingår i: Acta Diabetologica, ISSN 0940-5429, E-ISSN 1432-5233, Vol. 59, s. 761-772Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Aims Albuminuria is strongly associated with risk of renal dysfunction, cardiovascular disease and mortality. However, clinical guidelines diverge, and evidence is sparse on what risk factor levels regarding blood pressure, blood lipids and BMI are needed to prevent albuminuria in adolescents and young adults with type 1 diabetes. Methods A total of 9347 children and adults with type 1 diabetes [mean age 15.3 years and mean diabetes duration 1.4 years at start of follow-up] from The Swedish National Diabetes Registry were followed from first registration until end of 2017. Levels for risk factors for a risk increase in nephropathy were evaluated, and the gradient of risk per 1 SD (standard deviation) was estimated to compare the impact of each risk factor. Results During the follow-up period, 8610 (92.1%) remained normoalbuminuric, 737 (7.9%) individuals developed micro- or macroalbuminuria at any time period of whom 132 (17.9% of 737) individuals developed macroalbuminuria. Blood pressure >= 140/80 mmHg was associated with increased risk of albuminuria (p <= 0.0001), as were triglycerides >= 1.0 mmol/L (p = 0.039), total cholesterol >= 5.0 mmol/L (p = 0.0003), HDL < 1.0 mmol/L (p = 0.013), LDL 3.5- < 4.0 mmol/L (p = 0.020), and BMI >= 30 kg/m(2) (p = 0.033). HbA1c was the strongest risk factor for any albuminuria estimated by the measure gradient of risk per 1 SD, followed by diastolic blood pressure, triglycerides, systolic blood pressure, cholesterol and LDL. In patients with HbA1c > 65 mmol/mol (> 8.1%), blood pressure > 140/70 mmHg was associated with increased risk of albuminuria. Conclusions Preventing renal complications in adolescents and young adults with type 1 diabetes need avoidance at relatively high levels of blood pressure, blood lipids and BMI, whereas very tight control is not associated with further risk reduction. For patients with long-term poor glycaemic control, stricter blood pressure control is advocated.

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  • 64.
    Ahmadpour, Doryaneh
    et al.
    Region Östergötland, Närsjukvården i västra Östergötland, Medicinska specialistkliniken. Chalmers Univ Technol, Sweden.
    Kristoffersson, Anna
    Region Östergötland, Närsjukvården i västra Östergötland, Medicinska specialistkliniken.
    Fredrikson, Mats
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för inflammation och infektion. Linköpings universitet, Medicinska fakulteten, Forum Östergötland.
    Link, Yumin
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för neurobiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Neurologiska kliniken i Linköping.
    Eriksson, Anne
    Region Östergötland, Närsjukvården i västra Östergötland, Medicinska specialistkliniken.
    Iacobaeus, Ellen
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Landtblom, Anne-Marie
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för neurobiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Neurologiska kliniken i Linköping. Uppsala Univ, Sweden.
    Haghighi, Sara
    Region Östergötland, Sinnescentrum, Neurologiska kliniken i Linköping. Region Östergötland, Närsjukvården i västra Östergötland, Medicinska specialistkliniken.
    Inventory study of an early pandemic COVID-19 cohort in South-Eastern Sweden, focusing on neurological manifestations2023Ingår i: PLOS ONE, E-ISSN 1932-6203, Vol. 18, nr 1, artikel-id e0280376Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BackgroundNeurological manifestations in patients with COVID-19 have been reported previously as outcomes of the infection.The purpose of current study was to investigate the occurrence of neurological signs and symptoms in COVID-19 patients, in the county of ostergotland in southeastern Sweden. MethodsThis is a retrospective, observational cohort study. Data were collected between March 2020 and June 2020. Information was extracted from medical records by a trained research assistant and physician and all data were validated by a senior neurologist. ResultsSeventy-four percent of patients developed at least one neurological symptom during the acute phase of the infection. Headache (43%) was the most common neurological symptom, followed by anosmia and/or ageusia (33%), confusion (28%), hallucinations (17%), dizziness (16%), sleep disorders in terms of insomnia and OSAS (Obstructive Sleep Apnea) (9%), myopathy and neuropathy (8%) and numbness and tingling (5%). Patients treated in the ICU had a higher male presentation (73%). Several risk factors in terms of co-morbidities, were identified. Hypertension (54.5%), depression and anxiety (51%), sleep disorders in terms of insomnia and OSAS (30%), cardiovascular morbidity (28%), autoimmune diseases (25%), chronic lung diseases (24%) and diabetes mellitus type 2 (23%) founded as possible risk factors. ConclusionNeurological symptoms were found in the vast majority (74%) of the patients. Accordingly, attention to neurological, mental and sleep disturbances is warranted with involvement of neurological expertise, in order to avoid further complications and long-term neurological effect of COVID-19. Furthermore, risk factors for more severe COVID-19, in terms of possible co-morbidities that identified in this study should get appropriate attention to optimizing treatment strategies in COVID-19 patients.

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  • 65.
    Ahrens, Peter
    et al.
    Statens Serum Inst, Denmark.
    Andersen, Lee OBrien
    Statens Serum Inst, Denmark.
    Lilje, Berit
    Statens Serum Inst, Denmark.
    Johannesen, Thor Bech
    Statens Serum Inst, Denmark.
    Gomez Dahl, Ebba
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Medicincentrum, Hudkliniken i Östergötland. Statens Serum Inst, Denmark; Hlth Ctr Gullviksborg, Sweden.
    Baig, Sharmin
    Statens Serum Inst, Denmark.
    Jensen, Jorgen Skov
    Statens Serum Inst, Denmark.
    Falk, Lars
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Medicincentrum, Hudkliniken i Östergötland.
    Changes in the vaginal microbiota following antibiotic treatment forMycoplasma genitalium,Chlamydia trachomatisand bacterial vaginosis2020Ingår i: PLOS ONE, E-ISSN 1932-6203, Vol. 15, nr 7, artikel-id e0236036Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The human vagina harbor a rich microbiota. The optimal state is dominated by lactobacilli that help to maintain health and prevent various diseases. However, the microbiota may rapidly change to a polymicrobial state that has been linked to a number of diseases. In the present study, the temporal changes of the vaginal microbiota in patients treated for sexually transmitted diseases or bacterial vaginosis (BV) and in untreated controls were studied for 26 days. The patients included 52 women treated with azithromycin, tetracyclines or moxifloxacin for present or suspected infection withChlamydia trachomatisorMycoplasma genitalium. Women with concurrent BV were also treated with metronidazole. The controls were 10 healthy women of matching age. The microbiota was analyzed by 16S rRNA gene deep sequencing, specific qPCRs and microscopy. There was generally good correlation between Nugent score and community state type (CST) and qPCR confirmed the sequencing results. By sequencing, more than 600 different taxa were found, but only 33 constituted more than 1 parts per thousand of the sequences. In both patients and controls the microbiota could be divided into three different community state types, CST-I, CST-III and CST-IV. Without metronidazole, the microbiota remained relatively stable regarding CST although changes were seen during menstrual periods. Administration of metronidazole changed the microbiota from CST-IV to CST-III in approximately 50% of the treated patients. In contrast, the CST was generally unaffected by azithromycin or tetracyclines. In 30% of the BV patients,Gardnerella vaginaliswas not eradicated by metronidazole. The majority of women colonized withUreaplasma parvumremained positive after azithromycin whileU.urealyticumwas eradicated.

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  • 66.
    Ahs, Jill W.
    et al.
    Swedish Red Cross Univ, Sweden; Karolinska Inst, Sweden.
    Ranheim, Albertine
    Karolinska Inst, Sweden.
    Mattelin, Erica
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för barnafrid. Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Centrum för social och affektiv neurovetenskap. Linköpings universitet, Medicinska fakulteten.
    Eriksson, Henrik
    Univ West, Sweden.
    Mazaheri, Monir
    Karolinska Inst, Sweden; Sophiahemmet Univ, Sweden.
    Distance in Distant Care: Qualitative Content Analysis of Providers Experiences in Tele-Mental Care2023Ingår i: Journal of Medical Internet Research, E-ISSN 1438-8871, Vol. 25, artikel-id e38568Artikel i tidskrift (Övrigt vetenskapligt)
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  • 67.
    Ajiko, Mary Margaret
    et al.
    Soroti Reg Referral Hosp, Uganda; Karolinska Inst, Sweden.
    Kressner, Julia
    Karolinska Inst, Sweden.
    Matovu, Alphonsus
    Karolinska Inst, Sweden; Mubende Reg Referral Hosp, Uganda.
    Nordin, P.
    Umea Univ, Sweden; Ostersunds Sjukhus, Sweden.
    Wladis, Andreas
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Regionledningskontoret, Katastrofmedicinskt centrum.
    Löfgren, Jenny
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Surgical procedures for children in the public healthcare sector: a nationwide, facility-based study in Uganda2021Ingår i: BMJ Open, E-ISSN 2044-6055, Vol. 11, nr 7, artikel-id e048540Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective This study investigated the surgical services for children at the highest levels of the public healthcare sector in Uganda. The aim was to determine volumes and types of procedure performed and the patients and the human resource involved. Design The study was a facility-based, record review. Setting The study was carried out at the National Referral Hospital, all 14 regional referral hospitals and 14 general hospitals in Uganda, representing the highest levels of hospital in the public healthcare sector. Participants The subjects were children Results The study hospitals contribute with an average annual rate of paediatric surgery at 22.0 per 100 000 paediatric population. This is a fraction of the estimated need. Most of the procedures were performed for congenital anomalies (n=3111, 39.4%), inflammation and infection (n=2264, 28.7%) and trauma (n=1210, 15.3%). Specialist surgeons performed 60.3% (n=4758) of the procedures, and anaesthesia was administered by specialist physician anaesthetists in 11.6% (n=917) of the cases. Conclusions A variety of paediatric surgical procedures are performed in a relatively decentralised system throughout Uganda. Task shifting and task sharing of surgery and anaesthesia are widespread: a large proportion of surgical procedures was carried out by non-specialist physicians, with anaesthesia mostly delivered by non-physician anaesthetists. Reinforcing the capacity and promoting the expansion of the health facilities studied, in particular the general hospitals and regional referral hospitals, could help reduce the immense unmet need for surgical services for children in Uganda.

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  • 68.
    Ajiko, Mary Margaret
    et al.
    Department of Molecular Medicine and Surgery, Karolinska Institute, Solna, Sweden; Soroti Regional Referral Hospital, Soroti, Uganda.
    Weidman, Viking
    Uppsala University, Uppsala, Sweden.
    Nordin, Pär
    Department of Surgery and Perioperative Sciences, University of Umeå, Umeå, Sweden.
    Wladis, Andreas
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Regionledningskontoret, Katastrofmedicinskt centrum.
    Löfgren, Jenny
    Department of Molecular Medicine and Surgery, Karolinska Institute, Solna, Sweden.
    Correction: Prevalence of Paediatric Surgical Conditions in Eastern Uganda: A Cross-Sectional Study (Jan, 10.1007/s00268-021-06378-9, 2022)2022Ingår i: World Journal of Surgery, ISSN 0364-2313, E-ISSN 1432-2323, Vol. 46, nr 4, s. 966-966Artikel i tidskrift (Övrigt vetenskapligt)
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  • 69.
    Ajiko, Mary Margaret
    et al.
    Karolinska Inst, Sweden; Soroti Reg Referral Hosp, Uganda.
    Weidman, Viking
    Uppsala Univ, Sweden.
    Nordin, Pär
    Department of Surgery and Perioperative Sciences, University of Umeå, Umeå, Sweden.
    Wladis, Andreas
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Regionledningskontoret, Katastrofmedicinskt centrum.
    Löfgren, Jenny
    Karolinska Inst, Sweden.
    Prevalence of Paediatric Surgical Conditions in Eastern Uganda: A Cross-Sectional Study2022Ingår i: World Journal of Surgery, ISSN 0364-2313, E-ISSN 1432-2323, Vol. 46, nr 3, s. 701-708Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background The role of surgery in global health has gained greater attention in recent years. Approximately 1.8 billion children below 15 years live in low- and middle-income countries (LMIC). Many surgical conditions affect children. Therefore, paediatric surgery requires specific emphasis. Left unattended, the consequences can be dire. Despite this, there is a paucity of data regarding prevalence of surgical conditions in children in LMIC. The present objective was to investigate the prevalence of paediatric surgical conditions in children in a defined geographical area in Eastern Uganda. Method A cross-sectional study was carried out in the Iganga-Mayuge Health and Demographic Surveillance Site located in Eastern Uganda. Through a two-stage, cluster-based sampling process, 490 households from 49 villages were randomly selected, generating a study population of 1581 children. The childrens caregivers were interviewed, and the children were physically examined by two medical doctors to identify any surgical conditions. Results The interview was performed with 1581 children, and 1054 were physically examined. Among these, the overall prevalence of any surgical condition was 16.0 per cent (n = 169). Of these, 39 per cent had an unmet surgical need (66 of 169). This is equivalent to a 6.3 per cent prevalence of current unmet surgical need. The most common groups of surgical condition were congenital anomalies and trauma-related conditions. Conclusion Surgical conditions in children are common in eastern Uganda. The unmet need for surgery is high. With a growing population, the need for paediatric surgical capacity will increase even further. The health care system must be reinforced to provide services for children with surgical conditions if United Nations Sustainability Development Goal 3 is to be achieved by 2030.

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  • 70.
    Al Abri, Seif
    et al.
    Minist Hlth, Oman.
    Kasaeva, Thereza
    Who Global TB Programme, Switzerland.
    Migliori, Giovanni Battista
    Ist Clin Sci Maugeri IRCCS, Italy.
    Goletti, Delia
    Natl Inst Infect Dis Lazzaro Spallanzani IRCCS, Italy; ESCMID Study Grp Mycobacteria, Switzerland.
    Zenner, Dominik
    IOM, Belgium.
    Denholm, Justin
    Royal Melbourne Hosp, Australia; Victorian TB Programme, Australia.
    Al Maani, Amal
    Royal Hosp, Oman; Minist Hlth, Oman.
    Cirillo, Daniela Maria
    San Rafaele Sci Inst, Italy.
    Schön, Thomas
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för inflammation och infektion. Linköpings universitet, Medicinska fakulteten. Kalmar Cty Hosp, Sweden.
    Lillebaek, Troels
    Univ Copenhagen, Denmark.
    Al-Jardani, Amina
    Minist Hlth, Oman.
    Go, Un-Yeong
    Int TB Res Ctr, South Korea.
    Dias, Hannah Monica
    WHO Global TB Programme Unit Policy Strategy and In, Switzerland.
    Tiberi, Simon
    Barts Hlth NHS Trust, England; Queen Mary Univ London, England.
    Al Yaquobi, Fatma
    Minist Hlth, Oman.
    Khamis, Faryal Ali
    Minist Hlth, Oman.
    Kurup, Padmamohan
    Muscat Governorate, Oman.
    Wilson, Michael
    Zero TB Initiat, South Africa.
    Memish, Ziad
    Alfaisal Univ, Saudi Arabia; Emory Univ, GA 30322 USA.
    Al Maqbali, Ali
    North Bathinah Governorate, Oman.
    Akhtar, Muhammad
    WHO MENA Reg TB Programme, Egypt.
    Wejse, Christian
    Univ Aarhus, Denmark; ESCMID Study Grp Travel and Migrat, Switzerland.
    Petersen, Eskild
    Minist Hlth, Oman; Univ Aarhus, Denmark; ESCMID Emerging Infect Task Force, Switzerland.
    Tools to implement the World Health Organization End TB Strategy: Addressing common challenges in high and low endemic countries2020Ingår i: International Journal of Infectious Diseases, ISSN 1201-9712, E-ISSN 1878-3511, Vol. 92, s. S60-S68Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Aim: The purpose of this viewpoint is to summarize the advantages and constraints of the tools and strategies available for reducing the annual incidence of tuberculosis (TB) by implementing the World Health Organization (WHO) End TB Strategy and the linked WHO TB Elimination Framework, with special reference to Oman. Methods: The case-study was built based on the presentations and discussions at an international workshop on TB elimination in low incidence countries organized by the Ministry of Health, Oman, which took place from September 5 to September 7, 2019, and supported by the WHO and European Society of Clinical Microbiology and Infectious Diseases (ESCMID). Results: Existing tools were reviewed, including the screening of migrants for latent TB infection (LTBI) with interferon-gamma release assays, clinical examination for active pulmonary TB (APTB) including chest X-rays, organization of laboratory services, and the existing centres for mandatory health examination of pre-arrival or arriving migrants, including examination for APTB. The need for public-private partnerships to handle the burden of screening arriving migrants for active TB was discussed at length and different models for financing were reviewed. Conclusions: In a country with a high proportion of migrants from high endemic countries, screening for LTBI is of high priority. Molecular typing and the development of public-private partnerships are needed. (C) 2020 Published by Elsevier Ltd on behalf of International Society for Infectious Diseases.

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  • 71.
    Albadri, Zeyad
    et al.
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    AL Bayati, Doua
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten.
    Habel, Henrike
    Karolinska Inst, Sweden.
    Jerkovic Gulin, Sandra
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Div Dermatol & Venereol, Sweden.
    Groenhagen, Carina
    Lund Univ, Sweden.
    Seifert, Oliver
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Incidence of Dermatitis Herpetiformis in Sweden 2005 to 2018: A Nationwide Retrospective Cohort Study2023Ingår i: Acta Dermato-Venereologica, ISSN 0001-5555, E-ISSN 1651-2057, Vol. 103, artikel-id adv13210Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Dermatitis herpetiformis has been investigated in the past; however, only a limited number of studies have reported its incidence based on validated nationwide population-based registries. To address this gap, the aims of this study are to estimate the incidence of dermatitis herpetiformis in Sweden and to validate the National Patient Register (NPR) for diagnosis of dermatitis herpetiformis. A population-based open cohort study was conducted, including all patients diagnosed with dermatitis herpetiformis (International Classification of Diseases 10th revision; ICD-10 code L13.0) in Sweden from 2005 to 2018 (n = 1,724), identified from the NPR. The diagnosis of dermatitis herpetiformis in the NPR was validated using medical records, histopathological and immunopathological data, yielding a positive predictive value (PPV) of 62.5%. The mean annual incidence of dermatitis herpetiformis was 0.93/100,000 (95% confidence interval 0.79-1.08), female to male ratio 1:1, and mean age at diagnosis 60.9 years. In conclusion, this large nationwide cohort study showed a low validity for diagnosis of dermatitis herpetiformis in the NPR, and the adjusted incidence rate of dermatitis herpetiformis in Sweden was estimated to be 0.93/100,000, which is lower than that in previous Swedish studies.

  • 72.
    Albadri, Zeyad
    et al.
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Thorslund, Kristofer
    Karolinska Inst, Sweden.
    Habel, Henrike
    Karolinska Inst, Sweden.
    Seifert, Oliver
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Div Dermatol & Venereol, Sweden.
    Gronhagen, Carina
    Lund Univ, Sweden.
    Increased Risk of Squamous Cell Carcinoma of the Skin and Lymphoma Among 5,739 Patients with Bullous Pemphigoid: A Swedish Nationwide Cohort Study2020Ingår i: Acta Dermato-Venereologica, ISSN 0001-5555, E-ISSN 1651-2057, Vol. 100, artikel-id adv00289Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Evidence about the association of bullous pemphigoid and the risk of cancer is conflicting. Patients diagnosed with bullous pemphigoid (n = 5,739) between 2005 and 2016 were matched with a control cohort from the general population (n = 17,168) to estimate their overall and specific risk of cancer. The risk of squamous cell cancer of the skin (cSCC) was increased in patients with bullous pemphigoid (hazard ratio (HR) 1.3; 95% confidence interval (CI) 1.1-1.6). The risk of lymphoma within one year after bullous pemphigoid diagnosis was also increased (HR 3.1; 95% CI 1.3-7.6). While overall cancer risk prior to diagnosis of bullous pemphigoid was similar in cases and controls (prevalence odds ratio (POR) 1.0; 95% CI 0.9-1.0), the risk of male genital cancer within one year prior to diagnosis of bullous pemphigoid was lower in cases (POR 0.4; 95% CI 0.2-0.8). Clinicians must be aware of the increased risk of cSCC and lymphoma in patients with bullous pemphigoid.

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  • 73.
    Albanese-ONeill, Anastasia
    et al.
    Univ Florida, FL USA.
    Grimsmann, Julia M.
    Univ Ulm, Germany; German Ctr Diabet Res DZD, Germany.
    Svensson, Ann-Marie
    Ctr Registers Reg Vastra Gotaland, Sweden; Univ Gothenburg, Sweden.
    Miller, Kellee M.
    Jaeb Ctr Hlth Res, FL USA.
    Raile, Klemens
    Charite Univ Med Berlin, Germany.
    Åkesson, Karin
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten. Cty Hosp Ryhov, Sweden.
    Calhoun, Peter
    Jaeb Ctr Hlth Res, FL USA.
    Biesenbach, Beate
    Kepler Univ, Austria.
    Eeg-Olofsson, Katarina
    Univ Gothenburg, Sweden.
    Holl, Reinhard W.
    Univ Ulm, Germany; German Ctr Diabet Res DZD, Germany.
    Maahs, David M.
    Stanford Diabet Res Ctr, CA USA; Stanford Univ, CA USA.
    Hanas, Ragnar
    NU Hosp Grp, Sweden; Univ Gothenburg, Sweden.
    Changes in HbA1c Between 2011 and 2017 in Germany/Austria, Sweden, and the United States: A Lifespan Perspective2022Ingår i: Diabetes Technology & Therapeutics, ISSN 1520-9156, E-ISSN 1557-8593, Vol. 24, nr 1, s. 32-41Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Aims: This study assessed hemoglobin A1c (HbA1c) across the lifespan in people with type 1 diabetes (T1D) in Germany/Austria, Sweden, and the United States between 2011 and 2017 to ascertain temporal and age-related trends. Methods: Data from the Diabetes-Patienten-Verlaufsdokumentation (DPV) (n = 25,651 in 2011, n = 29,442 in 2017); Swedish Pediatric Diabetes Quality Registry (SWEDIABKIDS)/National Diabetes Register (NDR), (n = 44,474 in 2011, n = 53,690 in 2017); and T1D Exchange (n = 16,198 in 2011, n = 17,087 in 2017) registries were analyzed by linear regression to compare mean HbA1c overall and by age group. Results: Controlling for age, sex, and T1D duration, HbA1c increased in the United States between 2011 and 2017, decreased in Sweden, and did not change in Germany/Austria. Controlling for sex and T1D duration, mean HbA1c decreased between 2011 and 2017 in all age cohorts in Sweden (P < 0.001). In the United States, HbA1c stayed the same for participants <6 years and 45 to <65 years and increased in all other age groups (P < 0.05). In Germany/Austria, HbA1c stayed the same for participants <6 to <13 years and 18 to <25 years; decreased for participants ages 13 to <18 years (P < 0.01); and increased for participants >= 25 years (P < 0.05). Conclusions: The comparison of international trends in HbA1c makes it possible to identify differences, explore underlying causes, and share quality improvement processes. National quality improvement initiatives are well accepted in Europe but have yet to be implemented systematically in the United States. However, disparities created by the lack of universal access to health care coverage, unequal access to diabetes technologies (e.g., continuous glucose monitoring) regardless of insurance status, and high out-of-pocket cost for the underinsured ultimately limit the potential of quality improvement initiatives.

  • 74.
    Alehagen, Urban
    et al.
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för diagnostik och specialistmedicin. Linköpings universitet, Medicinska fakulteten.
    Aaseth, Jan
    Innlandet Hosp Trust, Norway.
    Lindahl, Tomas
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för klinisk kemi och farmakologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk kemi.
    Larsson, Anders
    Uppsala Univ, Sweden.
    Alexander, Jan
    Norwegian Inst Publ Hlth, Norway.
    Dietary Supplementation with Selenium and Coenzyme Q(10) Prevents Increase in Plasma D-Dimer While Lowering Cardiovascular Mortality in an Elderly Swedish Population2021Ingår i: Nutrients, E-ISSN 2072-6643, Vol. 13, nr 4, artikel-id 1344Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    A low intake of selenium is associated with increased cardiovascular mortality. This could be reduced by supplementation with selenium and coenzyme Q(10). D-dimer, a fragment of fibrin mirroring fibrinolysis, is a biomarker of thromboembolism, increased inflammation, endothelial dysfunction and is associated with cardiovascular mortality in ischemic heart disease. The objective was to examine the impact of selenium and coenzyme Q(10) on the level of D-dimer, and its relationship to cardiovascular mortality. D-dimer was measured in 213 individuals at the start and after 48 months of a randomised double-blind placebo-controlled trial with selenium yeast (200 mu g/day) and coenzyme Q(10) (200 mg/day) (n = 106) or placebo (n = 107). The follow-up time was 4.9 years. All included individuals were low in selenium (mean 67 mu g/L, SD 16.8). The differences in D-dimer concentration were evaluated by the use of T-tests, repeated measures of variance and ANCOVA analyses. At the end, a significantly lower D-dimer concentration was observed in the active treatment group in comparison with those on placebo (p = 0.006). Although D-dimer values at baseline were weakly associated with high-sensitive CRP, while being more strongly associated with soluble tumour necrosis factor receptor 1 and sP-selectin, controlling for these in the analysis there was an independent effect on D-dimer. In participants with a D-dimer level above median at baseline, the supplementation resulted in significantly lower cardiovascular mortality compared to those on placebo (p = 0.014). All results were validated with a persisting significant difference between the two groups. Therefore, supplementation with selenium and coenzyme Q(10) in a group of elderly low in selenium and coenzyme Q(10) prevented an increase in D-dimer and reduced the risk of cardiovascular mortality in comparison with the placebo group. The obtained results also illustrate important associations between inflammation, endothelial function and cardiovascular risk.

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  • 75.
    Alehagen, Urban
    et al.
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för diagnostik och specialistmedicin. Linköpings universitet, Medicinska fakulteten.
    Alexander, J.
    Norwegian Inst Publ Hlth, Norway.
    Aaseth, J.
    Innlandet Hosp Trust, Norway.
    Larsson, A.
    Uppsala Univ, Sweden.
    Lindahl, Tomas
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för klinisk kemi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk kemi.
    Significant decrease of von Willebrand factor and plasminogen activator inhibitor-1 by providing supplementation with selenium and coenzyme Q10 to an elderly population with a low selenium status2020Ingår i: European Journal of Nutrition, ISSN 1436-6207, E-ISSN 1436-6215, Vol. 59, s. 3581-3590Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose Endothelial dysfunction and inflammation are conditions which fuel atherosclerosis and ischaemic heart disease. We have previously reported reduced cardiovascular (CV) mortality following supplementation with selenium and coenzyme Q10 to 443 elderly individuals with low selenium status (mean 67 mu g/L) for 4 years. Here, we wanted to evaluate a possible association between the supplementation and the plasma concentrations of the von Willebrand factor (vWf), and the plasminogen activator inhibitor-1 (PAI-1), as they, besides other functions, are also strongly associated with endothelial function. Methods In this sub-study, 308 individuals (active substance: 157, placebo: 151) were included. Blood samples were drawn after 6 and 36 months and vWf and PAI-1 were determined in plasma by ELISA. Changes in concentrations of the biomarkers were evaluated by the use of T tests, repeated measures of variance, and ANCOVA analyses. Results The active treatment group presented a lower level of vWf after 36 months compared with the placebo group (1.08 U/mL vs. 5.10 U/mL; p = 0.0007). The results were validated through the repeated measures of variance evaluation. The PAI-1 levels showed an equally significant decrease in the active group (26.2 ng/mL vs. 49.2 ng/mL; p = 0.0002) and were also validated through repeated measures of variance evaluation. Conclusion In this sub-study on elderly receiving selenium and coenzyme Q10, or placebo we found significantly lower levels of vWf and PAI-1 in the active treatment group as compared to the placebo group. We interpret this as a better endothelial function because of the intervention, which accords with a previous finding of reduced CV mortality.

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  • 76.
    Alffenaar, J. W. C.
    et al.
    Univ Sydney, Australia; Westmead Hosp, Australia.
    Stocker, S. L.
    Univ Sydney, Australia; St Vincents Hosp, Australia; Univ NSW, Australia.
    Forsman, L. Davies
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Garcia-Prats, A.
    Stellenbosch Univ, South Africa; Univ Wisconsin, WI USA.
    Heysell, S. K.
    Univ Virginia, VA USA.
    Aarnoutse, R. E.
    Radboud Univ Nijmegen Med Ctr, Netherlands.
    Akkerman, O. W.
    Univ Groningen, Netherlands; Univ Groningen, Netherlands.
    Aleksa, A.
    Grodno State Med Univ, BELARUS.
    van Altena, R.
    Asian Harm Reduct Network AHRN, Myanmar; Med Act Myanmar MAM, Myanmar.
    de Onata, W. Arrazola
    Belgian Sci Inst Publ Hlth, Belgium.
    Bhavani, P. K.
    Indian Council Med Res Natl Inst Res TB, India.
    Vant Boveneind-Vrubleuskaya, N.
    Univ Groningen, Netherlands; Metropolitan Publ Hlth Serv, Netherlands.
    Carvalho, A. C. C.
    Fundacao Oswaldo Cruz, Brazil.
    Centis, R.
    Ist Ricovero & Cura Carattere Sci IRCCS, Italy.
    Chakaya, J. M.
    Kenyatta Univ, Kenya; Univ Liverpool Liverpool Sch Trop Med, England.
    Cirillo, D. M.
    IRCCS San Raffaele Sci Inst, Italy.
    Cho, J. G.
    Univ Sydney, Australia; Westmead Hosp, Australia; Parramatta Chest Clin, Australia.
    Ambrosio, L. D.
    Publ Hlth Consulting Grp, Switzerland.
    Dalcolmo, M. P.
    Funda Oswaldo Cruz Fiocruz, Brazil.
    Denti, P.
    Univ Cape Town, South Africa.
    Dheda, K.
    Univ Cape Town, South Africa; Univ Cape Town Lung Inst, South Africa; South African MRC Ctr Study Antimicrobial Resista, South Africa; London Sch Hyg & Trop Med, England.
    Fox, G. J.
    Univ Sydney, Australia; Woolcock Inst Med Res, Australia.
    Hesseling, A. C.
    Stellenbosch Univ, South Africa.
    Kim, H. Y.
    Univ Sydney, Australia; Westmead Hosp, Australia.
    Koser, C. U.
    Univ Cambridge, England.
    Marais, B. J.
    Univ Sydney, Australia; Childrens Hosp Westmead, Australia.
    Margineanu, I
    Univ Groningen, Netherlands.
    Martson, A. G.
    Univ Liverpool, England.
    Torrico, M. Munoz
    Inst Nacl Enfermedades Resp, Mexico.
    Nataprawira, H. M.
    Univ Padjadjaran, Indonesia.
    Ong, C. W. M.
    Natl Univ Singapore, Singapore; Natl Univ Singapore Hosp, Singapore.
    Otto-Knapp, R.
    German Cent Comm TB DZK, Germany.
    Peloquin, C. A.
    Univ Florida, FL USA.
    Silva, D. R.
    Univ Fed Rio Grande do Sul, Brazil.
    Ruslami, R.
    Univ Padjadjaran, Indonesia.
    Santoso, P.
    Univ Padjadjaran, Indonesia.
    Savic, R. M.
    Univ Calif San Francisco, CA USA.
    Singla, R.
    Natl Inst TB & Resp Dis, India.
    Svensson, E. M.
    Radboud Univ Nijmegen Med Ctr, Netherlands; Uppsala Univ, Sweden.
    Skrahina, A.
    Republican Res & Pract Ctr Pulmonol & TB, BELARUS.
    van Soolingen, D.
    Natl Inst Publ Hlth & Environm, Netherlands.
    Srivastava, S.
    Univ Texas Hlth Sci Ctr Tyler, TX USA.
    Tadolini, M.
    IRCCS Azienda Osped Univ Bologna, Italy; Alma Mater Studiorum Univ Bologna, Italy.
    Tiberi, S.
    Queen Mary Univ London, England.
    Thomas, T. A.
    Univ Virginia, VA USA.
    Udwadia, Z. F.
    PD Hinduja Natl Hosp & Med Res Ctr, India.
    Vu, D. H.
    Hanoi Univ Pharm, Vietnam.
    Zhang, W.
    Fudan Univ, Peoples R China.
    Mpagama, S. G.
    Kilimanjaro Christian Med Univ Coll, Tanzania; Kibongoto Infect Dis Hosp, Tanzania.
    Schön, Thomas
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för inflammation och infektion. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Medicincentrum, Infektionskliniken i Östergötland. Kalmar Cty Hosp, Sweden.
    Migliori, G. B.
    Grodno State Med Univ, BELARUS.
    Clinical standards for the dosing and management of TB drugs2022Ingår i: The International Journal of Tuberculosis and Lung Disease, ISSN 1027-3719, E-ISSN 1815-7920, Vol. 26, nr 6, s. 483-499Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Optimal drug dosing is important to ensure adequate response to treatment, prevent development of drug resistance and reduce drug toxicity. The aim of these clinical standards is to provide guidance on best practice for dosing and management of TB drugs.

    METHODS: A panel of 57 global experts in the fields of microbiology, pharmacology and TB care were identified; 51 participated in a Delphi process. A 5-point Likert scale was used to score draft standards. The final document represents the broad consensus and was approved by all participants.

    RESULTS: Six clinical standards were defined: Standard 1, defining the most appropriate initial dose for TB treatment; Standard 2, identifying patients who may be at risk of sub-optimal drug exposure; Standard 3, identifying patients at risk of developing drug-related toxicity and how best to manage this risk; Standard 4, identifying patients who can benefit from therapeutic drug monitoring (TDM); Standard 5, highlighting education and counselling that should be provided to people initiating TB treatment; and Standard 6, providing essential education for healthcare professionals. In addition, consensus research priorities were identified.

    CONCLUSION: This is the first consensus-based Clinical Standards for the dosing and management of TB drugs to guide clinicians and programme managers in planning and implementation of locally appropriate measures for optimal person-centred treatment to improve patient care.

  • 77.
    Alfsnes, Kristian
    et al.
    Norwegian Inst Publ Hlth, Norway.
    Lagerqvist, Nina
    Publ Hlth Agcy Sweden, Sweden.
    Vene, Sirkka
    Publ Hlth Agcy Sweden, Sweden.
    Bohlin, Jon
    Norwegian Inst Publ Hlth, Norway.
    Verner-Carlsson, Jenny
    Publ Hlth Agcy Sweden, Sweden.
    Ekqvist, David
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för inflammation och infektion. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Medicincentrum, Infektionskliniken i Östergötland.
    Brave, Andreas
    Publ Hlth Agcy Sweden, Sweden.
    Holmes, Edward C.
    Univ Sydney, Australia; Univ Sydney, Australia.
    Shi, Weifeng
    Shandong First Med Univ & Shandong Acad Med Sci, Peoples R China.
    Pettersson, John H-O
    Publ Hlth Agcy Sweden, Sweden; Univ Sydney, Australia; Univ Sydney, Australia; Uppsala Univ, Sweden.
    Retrospective meta-transcriptomic identification of severe dengue in a traveller returning from Africa to Sweden, 19902021Ingår i: One Health, ISSN 2352-7714, Vol. 12, artikel-id 100217Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Pathogens associated with haemorrhagic fever commonly have zoonotic origins. The first documented imported case of likely viral severe haemorrhagic fever in Sweden occurred in 1990. Despite extensive study, no aetiological agent was identified. Following retrospective investigation with total RNA-sequencing of samples collected between 7 and 36 days from onset of symptoms we identified dengue virus 3 (DENV-3) and a human pegivirus (HPgV). We conclude that the patient likely suffered from haemorrhagic symptoms due to an atypical severe and undiagnosed dengue infection.

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  • 78.
    Alfvén, Tobias
    et al.
    Karolinska institutet, Sverige; Sachsska barn- och ungdomssjukhuset, Sverige.
    Ekman, Anna-Theresia
    Karolinska institutet, Sverige; St Görans sjukhus, Stockholm, Sverige.
    Awil, Hana
    ST-läkare i allmänmedicin, Mora, Sverige.
    Holmer, Hampus
    Karolinska institutet, Stockholm, Sverige; Duke Global Health Institute, USA.
    Mia Ekström, Anna
    Karolinska institutet, Sverige; Karolinska universitetssjukhuset, Sverige.
    Preet, Raman
    Umeå universitet, Sverige.
    Agardh, Anette
    Lunds universitet, Sverige.
    Frielingsdorf Lundqvist, Helena
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Centrum för social och affektiv neurovetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Psykiatricentrum, Flyktingmedicinskt centrum.
    Agenda 2030 och målen för en hållbar utveckling angår oss alla [The 2030 Agenda for Sustainable Development - an important opportunity to improve global health]2020Ingår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 117Artikel, forskningsöversikt (Refereegranskat)
    Abstract [sv]

    Agenda 2030 och de 17 globala målen antogs av FN:s medlemsländer 2015. Målen utgör en gemensam plan för en hållbar utveckling och därigenom förbättrad hälsa i världen.

    Mellan 1990 och 2015 har hälsan i världen förbättrats. Medellivslängden har ökat och barna- och mödradödligheten har halverats. 

    Fortfarande dör över fem miljoner barn före sin fem­årsdag, 300 000 kvinnor dör i barnsäng varje år, antibiotikaresistens och icke-smittsamma sjukdomar ökar. Klimatförändringar har utsetts till århundradets största hälsohot. 

    När vi planerar för hur vårt samhälle och hälsosystem ska se ut efter covid-19-pandemin kan Agenda 2030 och dess fokus på internationellt samarbete och tvärprofessionella angreppssätt spela en viktig roll.

  • 79.
    Alghfeli, Latifa
    et al.
    Univ Sharjah, U Arab Emirates.
    Parambath, Divyasree
    Univ Sharjah, U Arab Emirates.
    Eldeen, Loaa A. Tag
    Suez Canal Univ, Egypt.
    El-Serafi, Ibrahim
    Ajman Univ, U Arab Emirates; Port Said Univ, Egypt.
    El-Serafi, Ahmed Taher
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Univ Sharjah, U Arab Emirates; Suez Canal Univ, Egypt.
    Non-additive effect of the DNA methylation inhibitor, 5-Aza-dC, and glass as a culture surface on osteogenic differentiation2022Ingår i: Heliyon, E-ISSN 2405-8440, Vol. 8, nr 12, artikel-id e12433Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The clinical need for bone regenerative solutions is expanding with increasing life expectancy and escalating incidence of accidents. Several strategies are being investigated to enhance the osteogenic differentiation of stem cells. We previously reported two different approaches for this purpose, in monolayer and three-dimensional cell culture. The first approach was based on pretreating cells with 5-Aza-dC, a DNA methylation inhibitor, before the applying the differentiation media. The second approach was based on culturing cells on a glass surface during differentiation. In this study, we investigated the potential effect of combining both methods. Our results sug-gested that both approaches were associated with decreasing global DNA methylation levels. Cells cultured as a monolayer on glass surface showed enhancement in alkaline phosphatase activity at day 10, while 5-Aza-dC pretreatment enhanced the activity at day 5, irrespective of the culture surface. In three-dimensional pellet cul-ture, 5-Aza-dC pretreatment enhanced osteogenesis through Runx-2 and TGF-beta 1 upregulation while the glass surface induced Osterix.Furthermore, pellets cultured on glass showed upregulation of a group of miRNAs, including pro-osteogenesis miR-20a and miR-148b and anti-osteogenesis miR-125b, miR-31, miR-138, and miR-133a. Interestingly, 5-Aza-dC was not associated with a change of miRNAs in cells cultured on tissue culture plastic but reverted the upregulated miRNAs on the glass to the basal level. This study confirms the two approaches for enhancing osteogenic differentiation and contradicts their combination.

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  • 80.
    Alghfeli, Latifa
    et al.
    Univ Sharjah, U Arab Emirates.
    Parambath, Divyasree
    Univ Sharjah, U Arab Emirates.
    Manzoor, Shaista
    Univ Sharjah, U Arab Emirates.
    Roach, Helmtrud I
    Univ Southampton, England.
    Oreffo, Richard O. C.
    Univ Southampton, England.
    El-Serafi, Ahmed Taher
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Univ Sharjah, U Arab Emirates; Suez Canal Univ, Egypt.
    Synthesis of scaffold-free, three dimensional, osteogenic constructs following culture of skeletal osteoprogenitor cells on glass surfaces2021Ingår i: Bone Reports, ISSN 2352-1872, Vol. 15, artikel-id 101143Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Efficient differentiation of stem cells into three-dimensional (3D) osteogenic construct is still an unmet challenge. These constructs can be crucial for patients with bone defects due to congenital or traumatic reasons. The modulation of cell fate and function as a consequence of interaction with the physical and chemical properties of materials is well known. Methods: The current study has examined the osteogenic differentiation potential of human skeletal populations following culture on glass surfaces, as a monolayer, or in glass tubes as a pellet culture. The 3D prosperities were assessed morphometrically and the differentiation was evaluated through molecular characterization as well as matrix formation. Results: Early temporal expression of alkaline phosphatase expression of skeletal populations was observed following culture on glass surfaces. Skeletal populations seeded on glass tubes, adhered as a monolayer to the tube base and subsequently formed 3D pellets at the air-media interface. The pellets cultured on glass displayed 4.9 +/- 1.3 times the weight and 2.9 +/- 0.1 the diameter of their counterpart cultured in plastic tubes and displayed enhanced production of osteogenic matrix proteins, such a collagen I and osteonectin. The size and weight of the pellets correlated with surface area in contrast to cell numbers seeded. Global DNA methylation level was decreased in pellets cultured on glass. In contrast, gene expression analysis confirmed upregulation extracellular matrix proteins and osteogenesis-related growth factors. Conclusion: This simple approach to the culture of skeletal cells on glass tubes provides a scaffold-free, 3D construct platform for generating pellets enabling analysis and evaluation of tissue development and integration of multiple constructs with implications for tissue repair and regenerative application on scale-up.

  • 81. Beställ onlineKöp publikationen >>
    Al-Hawasi, Abbas
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för sinnesorgan och kommunikation. Linköpings universitet, Medicinska fakulteten.
    Retinal ganglion cell examination with Optical Coherence Tomography reflects physiological and pathological changes in the eye and the brain.2023Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [sv]

    Den retinala ganglioncellen är belägen i den inre näthinnan och dess axoner, näthinnans nervfiberskikt (RNFL) eller nervfibrer, lämnar ögat för att bilda synnerven. Dessa ganglionceller utvecklas under fosterstadiet från framhjärnan och återskapar senare under utvecklingen förbindelser med olika delar av hjärnan som tjänar olika syften bland annat synen. Denna unika position och kopplingar gör det möjligt att undersöka dem med olika metoder. Optical Coherence Tomography (OCT) är en tillgänglig apparat på de flesta ögonkliniker och används vid olika ögonsjukdomar som grönstarr och sjukdomar i gula fläcken. Apparaten är lättmanövrerad, kostnadseffektiv och undersökningen kan göras i samband med kliniska besök. Undersökningen kan ge en detaljerad bild av näthinnas olika lager med en mikrometers precisionsnivå vid mätningar. I detta projekt har vi syftat till att se om undersökning av gangliecellerna med OCT kunde återspegla fysiologiska och patologiska förändringar i ögat och hjärnan.            

    I fall av synnervsinflammation (Arbete I), visar OCT-undersökningen tidig förtjockning av nervfibrerna följt av uttunning, det tog 6–9 månader för att minska till under den normala tjockleken utan att kunna skilja mellan verklig och falsk förtunning. Gangliecell-skiktet däremot visade en tjockleksminskning redan inom några veckor till 3 månader. Detta faktum ger ett snabbare och mer pålitligt resultat.

    I fall av tryck på synnerven på grund av ökat tryck i hjärnan, (idiopatisk Intrakraniell hypertoni) (Arbete II), förblir gangliecellslagret oförändrat och det finns ingen skillnad i nervfibrernas tjocklek jämfört med friska kontroller medan synnervshuvudets parameter som rim tjocklek och area, exkavationsvolymen och exkavation/synnervhuvudets-förhållande skiljer sig signifikant. Det bevisar att vid denna sjukdom, synnervshuvudet är först att bli påverkat medan gangliecell lagret visade ingen direkt eller bestående skada på nerven.   Vid Multipel skleros drabbas patienterna av sjukdomen ofta successivt och man behöver sätta in behandling för att förhindra funktionshinder. En grupp av dessa patienter slipper uppenbara funktionshinder även efter flera år av sjukdomen trots uteblivet behandlingsbehov. Den typen kallas för godartad eller benign (BMS).          

    I fall av godartad multipel skleros (Arbete IV) kan OCT undersökningen upptäcka och visa att ögonen som inte är drabbade av inflammation på synnerven har en årlig förtunning som liknar den hos en frisk population vilket är mindre uttalad än hos dem med MS med svårare sjukdomsförlopp. Med hjälp av undersökningen kan man bevisa ett mer godartat sjukdomsförlopp hos MS patienter och möjligen inget behov till behandling.

    I fall av fysiologiska faktorer som påverkar GCL i frisk population (Arbete III) visar OCT-undersökningen att det finns en signifikant förtunning av lagret med åldern men förtunningen är inte statistiskt signifikant när kön och axiell längd tas i beaktande. Män har en större gangliecell-volym än kvinnor och med åldern är det en signifikant minskning av volymen hos kvinnor, medan hos männen uteblir en signifikant förändring. Samma mönster ses i hjärnstorlek både med åldern och hos båda könen. En ökad axiell längd är associerad med tunnare ganglioncellskiktsvolym.        

    Sammanfattningsvis, en undersökning av retinala ganglieceller med OCT kan återspegla fysiologiska och patologiska förändringar i ögat och hjärnan och borde användas oftare för undersökning av patienter med olika sjukdomar. 

    Delarbeten
    1. Acute optic neuritis: retinal ganglion cell loss precedes retinal nerve fiber thinning.
    Öppna denna publikation i ny flik eller fönster >>Acute optic neuritis: retinal ganglion cell loss precedes retinal nerve fiber thinning.
    2015 (Engelska)Ingår i: Neurological Sciences, ISSN 1590-1874, E-ISSN 1590-3478, Vol. 36, nr 4, s. 617-620Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Optic neuritis (ON) causes axonal loss as reflected by thinning of retinal nerve fiber layer (RNFL) and can be tracked by optical coherence tomography (OCT) about 6 months after ON onset, when swelling of optic nerve head (ONH) has vanished. Changes of macular ganglion cell layer (GCL) thickness provide another window to track the disease process in ON. GCL thinning over time in relation to RNFL change after ON remains elusive. Using OCT, we followed 4 patients with acute unilateral isolated ON for more than 9 months. A diagnosis of multiple sclerosis (MS) was established in all 4 patients. First follow-up was 2-3 weeks after ON onset, and thereafter every 2-3 months. RNFL swelling peaked during first month after acute ON, followed by rapidly reduced swelling (pseudoatrophy) during following 2 months, and thereafter successively vanished 6 months after ON onset. GCL thinning was observed 1-3 months after ON onset, i.e. already during optic disk swelling and before real RNFL thinning. The results imply that quantifying GCL thickness provides opportunities to monitor early axonal loss and ON-to-MS progression, and facilitates distinguishing real atrophy from pseudoatrophy of RNFL after acute ON.

    Nationell ämneskategori
    Oftalmologi
    Identifikatorer
    urn:nbn:se:liu:diva-117096 (URN)10.1007/s10072-014-1982-3 (DOI)000351612200017 ()25311917 (PubMedID)
    Tillgänglig från: 2015-04-15 Skapad: 2015-04-15 Senast uppdaterad: 2023-11-16
    2. OCT measurements of optic nerve head changes in idiopathic intracranial hypertension
    Öppna denna publikation i ny flik eller fönster >>OCT measurements of optic nerve head changes in idiopathic intracranial hypertension
    2015 (Engelska)Ingår i: Clinical neurology and neurosurgery (Dutch-Flemish ed. Print), ISSN 0303-8467, E-ISSN 1872-6968, Vol. 130, s. 122-127Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Objective: Severity of papilledema and vision loss constitute a basis for therapeutic intervention in idiopathic intracranial hypertension (IIH), but both are often subjective and insensitive in guiding clinical management. The aim of this study was to identify reliable and sensitive measurements of optic nerve head (ONH) and macula, to provide objective guidance for prognostic evaluation and treatment in IIH. We analyzed potential of spectral domain optical coherence tomography (SD-OCT), to measure neuro-retinal rim thickness and area, optic cup-to-disc ratio (C/D) and cup volume of ONH which have not previously been reported in IIH. In parallel, thickness of peripapillary retinal nerve fiber layer (RNFL) and macular ganglion cell layer (GCL) together with inner plexiform layer (IPL) (GCL-IPL) were examined. Results: All 7 enrolled IIH patients had increased neuro-retinal rim thickness (p less than 0.01 for both eyes) and rim area (p less than 0.05), decreased C/D (p less than 0.01) and optic cup volume (p less than 0.01) when compared to findings in 18 sex- and age-matched healthy controls (HC). In a longitudinal study, two IIH patients were followed repetitively by SD-OCT before and after measurement of intracranial pressure (ICP) and removal of cerebrospinal fluid (CSF) by lumbar puncture. Rim thickness and area, C/D and optic cup volume remained altered. RNFL thickness may change with very high ICP, but not immediately after CSF removal. GCL-IPL thickness was unchanged irrespective of ICP change or CSF removal. Conclusion: SD-OCT allows detection of ONH changes even in subtle IIH without papilledema and has potential for routine use in IIH.

    Ort, förlag, år, upplaga, sidor
    Elsevier, 2015
    Nyckelord
    Cerebrospinal fluid; Idiopathic intracranial hypertension; Optic nerve head; Optical coherence tomography; Papilledema
    Nationell ämneskategori
    Oftalmologi
    Identifikatorer
    urn:nbn:se:liu:diva-116821 (URN)10.1016/j.clineuro.2014.12.021 (DOI)000350186200024 ()25614195 (PubMedID)
    Anmärkning

    Funding Agencies|County Council of Ostergotland, Sweden [LIO-121641, LiO-207242, LIO-276241]; Linkoping University

    Tillgänglig från: 2015-04-07 Skapad: 2015-04-07 Senast uppdaterad: 2023-11-16
    3. Retinal ganglion cell layer thickness and volume measured by OCT changes with age, sex, and axial length in a healthy population
    Öppna denna publikation i ny flik eller fönster >>Retinal ganglion cell layer thickness and volume measured by OCT changes with age, sex, and axial length in a healthy population
    2022 (Engelska)Ingår i: BMC Ophthalmology, E-ISSN 1471-2415, Vol. 22, nr 1, artikel-id 278Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Background The ganglion cell layer (GCL) measurements with Optical Coherence Tomography (OCT) are important for both ophthalmologists and neurologists because of their association with many ophthalmic and neurological diseases. Different factors can affect these measurements, such as brain pathologies, ocular axial length (AL) as well as age and sex. Studies conducted to measure the GCL have overlooked many of these factors. The purpose of this study is to examine the effect of age, sex, and AL on normal retinal GCL thickness and volume in a healthy population without any neurological diseases. Methods A prospective cross-sectional study was designed to measure GCL thickness and total volume with OCT with automated segmentation and manual correction where needed. Visual acuity, AL, and autorefraction were also measured. A mixed linear model was used to determine the association of the effect of the various parameters on the GCL thickness and volume. Results One hundred and sixteen eyes of 60 subjects (12-76 years of age, 55% female) were examined of which 77% had 0 +/- 2 D of spherical equivalent, and mean axial length was 23.86 mm. About 25% of the OCT-automated GCL measurements required manual correction. GCL thickness did not differ in similar anatomic regions in right and left eyes (P > 0.05). GCL volume was greater in males relative to females after adjustment for age and axial length (1.13 +/- 0.07 mm(3) for males vs 1.09 +/- 0.09 mm(3) for females; P = 0.031). GCL thickness differed between males and females in the inner retinal ring (P = 0.025) but not in the outer ring (P = 0.66). GCL volume declined with age (P = 0.031) but not after adjustment for sex and axial length (P = 0.138). GCL volume declined with longer axial length after adjustment for age and sex (P = 0.048). Conclusion Age, sex and axial length should be taken into consideration when measuring the GCL thickness and volume with OCT. Automated OCT segmentation should be reviewed for manual adjustments.

    Ort, förlag, år, upplaga, sidor
    BMC, 2022
    Nyckelord
    Ganglion cell layer (GCL); Retinal ganglion cell layer (RGCL); Ganglion cell layer thickness (GCLT); Optical coherence tomography (OCT); Ganglion cell volume (GCV)
    Nationell ämneskategori
    Oftalmologi
    Identifikatorer
    urn:nbn:se:liu:diva-186815 (URN)10.1186/s12886-022-02488-7 (DOI)000815497900004 ()35751115 (PubMedID)
    Anmärkning

    Funding Agencies|Linkoping University

    Tillgänglig från: 2022-07-04 Skapad: 2022-07-04 Senast uppdaterad: 2024-01-11
    4. Longitudinal Optical Coherence Tomography Measurement of Retinal Ganglion Cell and Nerve Fiber Layer to Assess Benign Course in Multiple Sclerosis
    Öppna denna publikation i ny flik eller fönster >>Longitudinal Optical Coherence Tomography Measurement of Retinal Ganglion Cell and Nerve Fiber Layer to Assess Benign Course in Multiple Sclerosis
    2023 (Engelska)Ingår i: Journal of Clinical Medicine, E-ISSN 2077-0383, Vol. 12, nr 6, artikel-id 2240Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    A benign form of multiple sclerosis (BMS) is not easily diagnosed, but changes of the retinal ganglion cell layer-inner plexiform layer (GCL-IPL) and retinal nerve fiber layer (RNFL) may be sensitive to the disease. The aim of this study was to use optical coherence tomography (OCT) to investigate longitudinal changes of GCL-IPL and RNFL in BMS. Eighteen patients with BMS and 22 healthy control (HC) subjects were included, with a mean follow-up period of 32.1 months in BMS and 34.3 months in HC. Mean disease duration in BMS was 23.3 years, with 14 patients left untreated. Unilateral optic neuritis (ON) was found in eight patients. Non-ON eyes showed thinner GCL-IPL layer in the BMS group relative to HC (p < 0.001). The thinning rate of GCL-IPL in non-ON BMS, however, was -0.19 +/- 0.15 mu m/year vs. 0 +/- 0.11 mu m/year for HC (p = 0.573, age-adjusted). Thinning rate of RNFL in non-ON BMS was -0.2 +/- 0.27 mu m/year vs. -0.05 +/- 0.3 mu m/year for HC (p = 0.454, age adjusted). Conclusions: Thinning rate of the GCL-IPL and RNFL in BMS is similar to the healthy population but differs from the thinning rate in relapsing-remitting MS, presenting a non-invasive OCT-based criterion for assessing a benign course in multiple sclerosis.

    Ort, förlag, år, upplaga, sidor
    MDPI, 2023
    Nyckelord
    retinal ganglion cell; retinal nerve fiber layer; ganglion cell complex; multiple sclerosis; benign multiple sclerosis; optical coherence tomography; biomarker; neural biomarker
    Nationell ämneskategori
    Oftalmologi
    Identifikatorer
    urn:nbn:se:liu:diva-193025 (URN)10.3390/jcm12062240 (DOI)000955333800001 ()36983241 (PubMedID)
    Tillgänglig från: 2023-04-14 Skapad: 2023-04-14 Senast uppdaterad: 2023-11-16
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  • 82.
    Al-Hawasi, Abbas
    et al.
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för sinnesorgan och kommunikation. Linköpings universitet, Medicinska fakulteten.
    Lagali, Neil
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för sinnesorgan och kommunikation. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Ögonkliniken US.
    Retinal ganglion cell layer thickness and volume measured by OCT changes with age, sex, and axial length in a healthy population2022Ingår i: BMC Ophthalmology, E-ISSN 1471-2415, Vol. 22, nr 1, artikel-id 278Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background The ganglion cell layer (GCL) measurements with Optical Coherence Tomography (OCT) are important for both ophthalmologists and neurologists because of their association with many ophthalmic and neurological diseases. Different factors can affect these measurements, such as brain pathologies, ocular axial length (AL) as well as age and sex. Studies conducted to measure the GCL have overlooked many of these factors. The purpose of this study is to examine the effect of age, sex, and AL on normal retinal GCL thickness and volume in a healthy population without any neurological diseases. Methods A prospective cross-sectional study was designed to measure GCL thickness and total volume with OCT with automated segmentation and manual correction where needed. Visual acuity, AL, and autorefraction were also measured. A mixed linear model was used to determine the association of the effect of the various parameters on the GCL thickness and volume. Results One hundred and sixteen eyes of 60 subjects (12-76 years of age, 55% female) were examined of which 77% had 0 +/- 2 D of spherical equivalent, and mean axial length was 23.86 mm. About 25% of the OCT-automated GCL measurements required manual correction. GCL thickness did not differ in similar anatomic regions in right and left eyes (P > 0.05). GCL volume was greater in males relative to females after adjustment for age and axial length (1.13 +/- 0.07 mm(3) for males vs 1.09 +/- 0.09 mm(3) for females; P = 0.031). GCL thickness differed between males and females in the inner retinal ring (P = 0.025) but not in the outer ring (P = 0.66). GCL volume declined with age (P = 0.031) but not after adjustment for sex and axial length (P = 0.138). GCL volume declined with longer axial length after adjustment for age and sex (P = 0.048). Conclusion Age, sex and axial length should be taken into consideration when measuring the GCL thickness and volume with OCT. Automated OCT segmentation should be reviewed for manual adjustments.

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  • 83.
    Al-Hawasi, Abbas
    et al.
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för sinnesorgan och kommunikation. Linköpings universitet, Medicinska fakulteten.
    Lagali, Neil
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för sinnesorgan och kommunikation. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Ögonkliniken US.
    Fagerholm, Per
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för sinnesorgan och kommunikation. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Ögonkliniken US.
    Link, Yumin
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för neurobiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Neurologiska kliniken i Linköping.
    Longitudinal Optical Coherence Tomography Measurement of Retinal Ganglion Cell and Nerve Fiber Layer to Assess Benign Course in Multiple Sclerosis2023Ingår i: Journal of Clinical Medicine, E-ISSN 2077-0383, Vol. 12, nr 6, artikel-id 2240Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    A benign form of multiple sclerosis (BMS) is not easily diagnosed, but changes of the retinal ganglion cell layer-inner plexiform layer (GCL-IPL) and retinal nerve fiber layer (RNFL) may be sensitive to the disease. The aim of this study was to use optical coherence tomography (OCT) to investigate longitudinal changes of GCL-IPL and RNFL in BMS. Eighteen patients with BMS and 22 healthy control (HC) subjects were included, with a mean follow-up period of 32.1 months in BMS and 34.3 months in HC. Mean disease duration in BMS was 23.3 years, with 14 patients left untreated. Unilateral optic neuritis (ON) was found in eight patients. Non-ON eyes showed thinner GCL-IPL layer in the BMS group relative to HC (p < 0.001). The thinning rate of GCL-IPL in non-ON BMS, however, was -0.19 +/- 0.15 mu m/year vs. 0 +/- 0.11 mu m/year for HC (p = 0.573, age-adjusted). Thinning rate of RNFL in non-ON BMS was -0.2 +/- 0.27 mu m/year vs. -0.05 +/- 0.3 mu m/year for HC (p = 0.454, age adjusted). Conclusions: Thinning rate of the GCL-IPL and RNFL in BMS is similar to the healthy population but differs from the thinning rate in relapsing-remitting MS, presenting a non-invasive OCT-based criterion for assessing a benign course in multiple sclerosis.

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  • 84.
    Ali, A.
    et al.
    Malmo Univ, Sweden; Malmo Univ, Sweden; Speximo AB, Sweden.
    Skedung, L.
    RISE Res Inst Sweden Bioecon & Hlth, Sweden.
    Burleigh, S.
    Lund Univ, Sweden.
    Lavant, E.
    Malmo Univ, Sweden; Malmo Univ, Sweden.
    Ringstad, L.
    RISE Res Inst Sweden Bioecon & Hlth, Sweden.
    Anderson, Chris D
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Medicincentrum, Hudkliniken i Östergötland.
    Wahlgren, M.
    Lund Univ, Sweden.
    Engblom, J.
    Malmo Univ, Sweden; Malmo Univ, Sweden.
    Relationship between sensorial and physical characteristics of topical creams: A comparative study on effects of excipients2022Ingår i: International Journal of Pharmaceutics, ISSN 0378-5173, E-ISSN 1873-3476, Vol. 613, artikel-id 121370Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Rising consumer demands for safer, more natural, and sustainable topical products have led to increased interest in finding alternative excipients, while retaining functionality and cosmetic appeal. Particle-stabilized Pickering creams have emerged as possible alternatives to replace traditional surfactant-stabilized creams and are thus one of the focuses in this study. The aim of this paper was to study relationships between sensorial characteristics and physical properties to understand how different excipients affect these aspects, comparing one starch particle-stabilized and three surfactant-stabilized formulations. A human panel was used to evaluate sensorial perception, while physical properties were deduced by rheology and tactile friction, together with in vivo and ex vivo skin hydration measurements. The results show that sensorial attributes related to the application phase can be predicted with rheology, while afterfeel attributes can be predicted with tactile friction studies. Differences in rheological and sensory properties among surfactant-based creams could mainly be attributed to the type of emollients used, presence of thickeners and surfactant composition. Differences between surfactant-based creams and a Pickering cream were more evident in relation to the afterfeel perception. Presence of starch particles in the residual film on skin results in high tactile friction and low perception of residual coating, stickiness, greasiness, and slipperiness in sensorial afterfeel.

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  • 85.
    Ali, Abshir A.
    et al.
    East Africa Univ, Somalia.
    Aalto, Mikko
    Bosaso Gen Hosp, Somalia.
    Jonasson, Jon
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk genetik.
    Osman, Abdimajid
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för klinisk kemi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk kemi.
    Genome-wide analyses disclose the distinctive HLA architecture and the pharmacogenetic landscape of the Somali population2020Ingår i: Scientific Reports, E-ISSN 2045-2322, Vol. 10, nr 1, artikel-id 5652Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    African populations are underrepresented in medical genomics studies. For the Somali population, there is virtually no information on genomic markers with significance to precision medicine. Here, we analyzed nearly 900,000 genomic markers in samples collected from 95 unrelated individuals in the North Eastern Somalia. ADMIXTURE program for estimation of individual ancestries revealed a homogenous Somali population. Principal component analysis with PLINK software showed approximately 60% East African and 40% West Eurasian genes in the Somali population, with a close relation to the Cushitic and Semitic speaking Ethiopian populations. We report the unique features of human leukocyte antigens (HLA) in the Somali population, which seem to differentiate from all other neighboring regions compared. Current study identified high prevalence of the diabetes type 1 (T1D) predisposing HLA DR-DQ haplotypes in Somalia. This finding may explain the increased T1D risk observed among Somali children. In addition, ethnic Somalis were found to host the highest frequencies observed thus far for several pharmacogenetic variants, including UGT1A4*2. In conclusion, we report that the Somali population displays genetic traits of significance to health and disease. The Somali dataset is publicly available and will add more information to the few genomic datasets available for African populations.

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  • 86.
    Ali, Adnan
    et al.
    Univ Lancaster, England.
    Ahle, Margareta
    Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Röntgenkliniken i Linköping. Linköpings universitet, Institutionen för hälsa, medicin och vård.
    Björnsson, Bergthor
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Kirurgiska kliniken US.
    Sandström, Per
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Kirurgiska kliniken US.
    Portal vein embolization with N-butyl cyanoacrylate glue is superior to other materials: a systematic review and meta-analysis2021Ingår i: European Radiology, ISSN 0938-7994, E-ISSN 1432-1084, Vol. 31, nr 8, s. 5464-5478Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Objectives It remains uncertain which embolization material is best for portal vein embolization (PVE). We investigated the various materials for effectiveness in inducing future liver remnant (FLR) hypertrophy, technical and growth success rates, and complication and resection rates. Methods A systematic review from 1998 to 2019 on embolization materials for PVE was performed on Pubmed, Embase, and Cochrane. FLR growth between the two most commonly used materials was compared in a random effects meta-analysis. In a separate analysis using local data (n = 52), n-butyl cyanoacrylate (NBCA) was compared with microparticles regarding costs, radiation dose, and procedure time. Results In total, 2896 patients, 61.0 +/- 4.0 years of age and 65% male, from 51 papers were included in the analysis. In 61% of the patients, either NBCA or microparticles were used for embolization. The remaining were treated with ethanol, gelfoam, or sclerosing agents. The FLR growth with NBCA was 49.1% +/- 29.7 compared to 42.2% +/- 40 with microparticles (p = 0.037). The growth success rate with NBCA vs microparticles was 95.3% vs 90.7% respectively (p < 0.001). There were no differences in major complications between NBCA and microparticles. In the local analysis, NBCA (n = 41) entailed shorter procedure time and reduced fluoroscopy time (p < 0.001), lower radiation exposure (p < 0.01), and lower material costs (p < 0.0001) than microparticles (n = 11). Conclusion PVE with NBCA seems to be the best choice when combining growth of the FLR, procedure time, radiation exposure, and costs.

  • 87.
    Ali, Tahir
    et al.
    Univ Calgary, Canada.
    Klein, Antonia N.
    Univ Calgary, Canada.
    McDonald, Keegan
    Univ Calgary, Canada.
    Johansson, Lovisa
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för neurobiologi. Linköpings universitet, Medicinska fakulteten.
    Mukherjee, Priyanka Ganguli
    Univ Calgary, Canada.
    Hallbeck, Martin
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för neurobiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk patologi.
    Doh-ura, Katsumi
    Tohoku Univ, Japan.
    Schatzl, Hermann M.
    Univ Calgary, Canada.
    Gilch, Sabine
    Univ Calgary, Canada.
    Cellulose ether treatment inhibits amyloid beta aggregation, neuroinflammation and cognitive deficits in transgenic mouse model of Alzheimers disease2023Ingår i: Journal of Neuroinflammation, ISSN 1742-2094, E-ISSN 1742-2094, Vol. 20, nr 1, artikel-id 177Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Alzheimers disease (AD) is an incurable, progressive and devastating neurodegenerative disease. Pathogenesis of AD is associated with the aggregation and accumulation of amyloid beta (A & beta;), a major neurotoxic mediator that triggers neuroinflammation and memory impairment. Recently, we found that cellulose ether compounds (CEs) have beneficial effects against prion diseases by inhibiting protein misfolding and replication of prions, which share their replication mechanism with A & beta;. CEs are FDA-approved safe additives in foods and pharmaceuticals. Herein, for the first time we determined the therapeutic effects of the representative CE (TC-5RW) in AD using in vitro and in vivo models. Our in vitro studies showed that TC-5RW inhibits A & beta; aggregation, as well as neurotoxicity and immunoreactivity in A & beta;-exposed human and murine neuroblastoma cells. In in vivo studies, for the first time we observed that single and weekly TC-5RW administration, respectively, improved memory functions of transgenic 5XFAD mouse model of AD. We further demonstrate that TC-5RW treatment of 5XFAD mice significantly inhibited A & beta; oligomer and plaque burden and its associated neuroinflammation via regulating astrogliosis, microgliosis and proinflammatory mediator glial maturation factor beta (GMF & beta;). Additionally, we determined that TC-5RW reduced lipopolysaccharide-induced activated gliosis and GMF & beta; in vitro. In conclusion, our results demonstrate that CEs have therapeutic effects against A & beta; pathologies and cognitive impairments, and direct, potent anti-inflammatory activity to rescue neuroinflammation. Therefore, these FDA-approved compounds are effective candidates for developing therapeutics for AD and related neurodegenerative diseases associated with protein misfolding.

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  • 88.
    Ali, Zaheer
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten.
    Cui, Dongmei
    Sun Yat Sen Univ, Peoples R China.
    Yang, Yunlong
    Fudan Univ, Peoples R China.
    Tracey-White, Dhani
    UCL Inst Ophthalmol, England.
    Vazquez Rodriguez, Gabriela
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Moosajee, Mariya
    UCL Inst Ophthalmol, England.
    Ju, Rong
    Sun Yat Sen Univ, Peoples R China.
    Li, Xuri
    Sun Yat Sen Univ, Peoples R China.
    Cao, Yihai
    Karolinska Inst, Sweden.
    Jensen, Lasse
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för diagnostik och specialistmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk farmakologi.
    Synchronized tissue-scale vasculogenesis and ubiquitous lateral sprouting underlie the unique architecture of the choriocapillaris2020Ingår i: Developmental Biology, ISSN 0012-1606, E-ISSN 1095-564X, Vol. 457, nr 2, s. 206-214Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The choriocapillaris is an exceptionally high density, two-dimensional, sheet-like capillary network, characterized by the highest exchange rate of nutrients for waste products per area in the organism. These unique morphological and physiological features are critical for supporting the extreme metabolic requirements of the outer retina needed for vision. The developmental mechanisms and processes responsible for generating this unique vascular network remain, however, poorly understood. Here we take advantage of the zebrafish as a model organism for gaining novel insights into the cellular dynamics and molecular signaling mechanisms involved in the development of the choriocapillaris. We show for the first time that zebrafish have a choriocapillaris highly similar to that in mammals, and that it is initially formed by a novel process of synchronized vasculogenesis occurring simultaneously across the entire outer retina. This initial vascular network expands by un-inhibited sprouting angiogenesis whereby all endothelial cells adopt tip-cell characteristics, a process which is sustained throughout embryonic and early post-natal development, even after the choriocapillaris becomes perfused. Ubiquitous sprouting was maintained by continuous VEGF-VEGFR2 signaling in endothelial cells delaying maturation until immediately before stages where vision becomes important for survival, leading to the unparalleled high density and lobular structure of this vasculature. Sprouting was throughout development limited to two dimensions by Bruchs membrane and the sclera at the anterior and posterior surfaces respectively. These novel cellular and molecular mechanisms underlying choriocapillaris development were recapitulated in mice. In conclusion, our findings reveal novel mechanisms underlying the development of the choriocapillaris during zebrafish and mouse development. These results may explain the uniquely high density and sheet-like organization of this vasculature.

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  • 89.
    Ali, Zaheer
    et al.
    BioReperia AB, Linkoping, Sweden.
    Vildevall, Malin
    BioReperia AB, Linkoping, Sweden.
    Rodriguez, Gabriela Vazquez
    BioReperia AB, Linkoping, Sweden.
    Tandiono, Decky
    BioReperia AB, Linkoping, Sweden.
    Vamvakaris, Ioannis
    Athens Chest Hosp Sotiria, Greece.
    Evangelou, Georgios
    Natl Kapodistrian Univ Athens, Greece.
    Lolas, Georgios
    Natl Kapodistrian Univ Athens, Greece; Catalan Inst Oncol ICO, Spain.
    Syrigos, Konstantinos N.
    Natl Kapodistrian Univ Athens, Greece.
    Villanueva, Alberto
    InCELLiA PC, Greece; Xenopat SL, Spain.
    Wick, Michael
    XenoSTART, TX USA.
    Omar, Shenga
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för diagnostik och specialistmedicin. Linköpings universitet, Medicinska fakulteten.
    Erkstam, Anna
    BioReperia AB, Linkoping, Sweden.
    Schueler, Julia
    Charles River Labs, Germany.
    Fahlgren, Anna
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. BioReperia AB, Linkoping, Sweden.
    Jensen, Lasse
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för diagnostik och specialistmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk farmakologi. BioReperia AB, Linkoping, Sweden.
    Zebrafish patient-derived xenograft models predict lymph node involvement and treatment outcome in non-small cell lung cancer2022Ingår i: Journal of Experimental & Clinical Cancer Research, E-ISSN 1756-9966, Vol. 41, nr 1, artikel-id 58Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background Accurate predictions of tumor dissemination risks and medical treatment outcomes are critical to personalize therapy. Patient-derived xenograft (PDX) models in mice have demonstrated high accuracy in predicting therapeutic outcomes, but methods for predicting tumor invasiveness and early stages of vascular/lymphatic dissemination are still lacking. Here we show that a zebrafish tumor xenograft (ZTX) platform based on implantation of PDX tissue fragments recapitulate both treatment outcome and tumor invasiveness/dissemination in patients, within an assay time of only 3 days. Methods Using a panel of 39 non-small cell lung cancer PDX models, we developed a combined mouse-zebrafish PDX platform based on direct implantation of cryopreserved PDX tissue fragments into zebrafish embryos, without the need for pre-culturing or expansion. Clinical proof-of-principle was established by direct implantation of tumor samples from four patients. Results The resulting ZTX models responded to Erlotinib and Paclitaxel, with similar potency as in mouse-PDX models and the patients themselves, and resistant tumors similarly failed to respond to these drugs in the ZTX system. Drug response was coupled to elevated expression of EGFR, Mdm2, Ptch1 and Tsc1 (Erlotinib), or Nras and Ptch1 (Paclitaxel) and reduced expression of Egfr, Erbb2 and Foxa (Paclitaxel). Importantly, ZTX models retained the invasive phenotypes of the tumors and predicted lymph node involvement of the patients with 91% sensitivity and 62% specificity, which was superior to clinically used tests. The biopsies from all four patient tested implanted successfully, and treatment outcome and dissemination were quantified for all patients in only 3 days. Conclusions We conclude that the ZTX platform provide a fast, accurate, and clinically relevant system for evaluation of treatment outcome and invasion/dissemination of PDX models, providing an attractive platform for combined mouse-zebrafish PDX trials and personalized medicine.

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  • 90.
    Ali, Zaheer
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten.
    Zang, Jingjing
    Univ Zurich, Switzerland.
    Lagali, Neil S
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för sinnesorgan och kommunikation. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Ögonkliniken US.
    Schmitner, Nicole
    Univ Innsbruck, Austria.
    Salvenmoser, Willi
    Univ Innsbruck, Austria.
    Mukwaya, Anthony
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för sinnesorgan och kommunikation. Linköpings universitet, Medicinska fakulteten.
    Neuhauss, Stephan C. F.
    Univ Zurich, Switzerland.
    Jensen, Lasse
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för diagnostik och specialistmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk farmakologi.
    Kimmel, Robin A.
    Univ Innsbruck, Austria.
    Photoreceptor Degeneration Accompanies Vascular Changes in a Zebrafish Model of Diabetic Retinopathy2020Ingår i: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 61, nr 2, artikel-id UNSP 43Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    PURPOSE. Diabetic retinopathy (DR) is a leading cause of vision impairment and blindness worldwide in the working-age population, and the incidence is rising. Until now it has been difficult to define initiating events and disease progression at the molecular level, as available diabetic rodent models do not present the full spectrum of neural and vascular pathologies. Zebrafish harboring a homozygous mutation in the pancreatic transcription factor pdx1 were previously shown to display a diabetic phenotype from larval stages through adulthood. In this study, pdx1 mutants were examined for retinal vascular and neuronal pathology to demonstrate suitability of these fish for modeling DR. METHODS. Vessel morphology was examined in pdx1 mutant and control fish expressing the fli1a:EGFP transgene. We further characterized vascular and retinal phenotypes in mutants and controls using immunohistochemistry, histology, and electron microscopy. Retinal function was assessed using electroretinography. RESULTS. Pdx1 mutants exhibit clear vascular phenotypes at 2 months of age, and disease progression, including arterial vasculopenia, capillary tortuosity, and hypersprouting, could be detected at stages extending over more than 1 year. Neural-retinal pathologies are consistent with photoreceptor dysfunction and loss, but do not progress to blindness. CONCLUSIONS. This study highlights pdx1 mutant zebrafish as a valuable complement to rodent and other mammalian models of DR, in particular for research into the mechanistic interplay of diabetes with vascular and neuroretinal disease. They are furthermore suited for molecular studies to identify new targets for treatment of early as well as late DR.

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  • 91.
    Alim, Md Abdul
    et al.
    Uppsala Univ, Sweden.
    Grujic, Mirjana
    Uppsala Univ, Sweden.
    Ackerman, Paul W.
    Karolinska Inst, Sweden.
    Kristiansson, Per
    Uppsala Univ, Sweden.
    Eliasson, Pernilla T.
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten.
    Peterson, Magnus
    Uppsala Univ, Sweden; Acad Primary Hlth Care, Sweden.
    Pejler, Gunnar
    Uppsala Univ, Sweden; Swedish Univ Agr Sci, Sweden.
    Glutamate triggers the expression of functional ionotropic and metabotropic glutamate receptors in mast cells2021Ingår i: Cellular & Molecular Immunology, ISSN 1672-7681, E-ISSN 2042-0226, Vol. 18, s. 2383-2392Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Mast cells are emerging as players in the communication between peripheral nerve endings and cells of the immune system. However, it is not clear the mechanism by which mast cells communicate with peripheral nerves. We previously found that mast cells located within healing tendons can express glutamate receptors, raising the possibility that mast cells may be sensitive to glutamate signaling. To evaluate this hypothesis, we stimulated primary mast cells with glutamate and showed that glutamate induced the profound upregulation of a panel of glutamate receptors of both the ionotropic type (NMDAR1, NMDAR2A, and NMDAR2B) and the metabotropic type (mGluR2 and mGluR7) at both the mRNA and protein levels. The binding of glutamate to glutamate receptors on the mast cell surface was confirmed. Further, glutamate had extensive effects on gene expression in the mast cells, including the upregulation of pro-inflammatory components such as IL-6 and CCL2. Glutamate also induced the upregulation of transcription factors, including Egr2, Egr3 and, in particular, FosB. The extensive induction of FosB was confirmed by immunofluorescence assessment. Glutamate receptor antagonists abrogated the responses of the mast cells to glutamate, supporting the supposition of a functional glutamate-glutamate receptor axis in mast cells. Finally, we provide in vivo evidence supporting a functional glutamate-glutamate receptor axis in the mast cells of injured tendons. Together, these findings establish glutamate as an effector of mast cell function, thereby introducing a novel principle for how cells in the immune system can communicate with nerve cells.

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  • 92.
    Alim, Md Abdul
    et al.
    Uppsala Univ, Sweden; Uppsala Univ, Sweden.
    Grujic, Mirjana
    Uppsala Univ, Sweden.
    Ackermann, Paul W.
    Karolinska Inst, Sweden.
    Kristiansson, Per
    Uppsala Univ, Sweden.
    Blomgran, Parmis
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten.
    Eliasson, Pernilla T.
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten.
    Peterson, Magnus
    Uppsala Univ, Sweden; Acad Primary Hlth Care, Sweden.
    Pejler, Gunnar
    Uppsala Univ, Sweden; Swedish Univ Agr Sciences, Sweden.
    Correction: Glutamate triggers the expression of functional ionotropic and metabotropic glutamate receptors in mast cells (vol 74, pg 613, 2020)Ingår i: Cellular & Molecular Immunology, ISSN 1672-7681, E-ISSN 2042-0226, s. 2020-2020Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    An amendment to this paper has been published and can be accessed via a link at the top of the paper.

  • 93.
    Aljabery, Firas
    et al.
    Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Urologiska kliniken i Östergötland. Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi.
    Shabo, Ivan
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Saudi, Aus
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Urologiska kliniken i Östergötland.
    Holmbom, Martin
    Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Urologiska kliniken i Östergötland. Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi.
    Olson, Hans
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk patologi.
    Jahnson, Staffan
    Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Urologiska kliniken i Östergötland. Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi.
    The emerging role of cell cycle protein p53 expression by tumor cells and M2-macrophage infiltration in urinary bladder cancer2023Ingår i: Urologic Oncology, ISSN 1078-1439, E-ISSN 1873-2496, Vol. 41, nr 3Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose: To investigate the association between p53 expression in tumor cells and intratumoral macrophage infiltration in muscle-invasive urinary bladder cancer (MIBC) in relation to clinical and pathological variables and outcomes after radical cystectomy. Methods: Tumor specimens of the primary tumor from patients treated with radical cystectomy for MIBC were immunostained with the M2-macrophage-specific marker CD163 and the cell cycle protein p53. The expression of these markers was analyzed in relation to patients and tumor characteristics and outcome. Results: Out of 100 patients with urinary bladder cancer (UBC) pathological stage T1-4 N0-3 M0, 77% were men. The patients had a median age of 69 years and 80% had nonorgan-confined tumors (pT3-4). Lymph node metastasis was found in 42 (42%) of all patients. P53-positive expressions were found in 63 (63%) patients. Strong macrophage infiltration in the tumor microenvironment was shown in 74 (74%) patients. Combinations of CD163/p53 status were as follows: CD163+/p53+, 50%; CD163+/p53-, 24%; CD163-/p53+, 13%; and CD163-/p53-, 13%. Patients with CD163+/P53+ had higher proportions of organ-confined tumors. Conclusions: In the present series of patients with MIBC treated with cystectomy, we found that high CD163+ macrophage infiltration in the tumor micro-environment often was combined with p53+ cancer cells. This simultaneous expression of p53 by tumor cells and increased infiltration of M2-macrophages in the tumor microenvironment was associated with improved CSS, which might indicate a possible protective effect of M2 macrophages in p53+ tumors. Further investigations are needed to explore the biological relation between mutational burden and immune profile in MIBC. (c) 2022 Published by Elsevier Inc.

  • 94.
    Alkaissi, Lina Y.
    et al.
    Linköpings universitet, Medicinska fakulteten. Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi.
    Winberg Tinnerfelt, Martin
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten.
    Heil, Stéphanie
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för molekylär medicin och virologi. Linköpings universitet, Medicinska fakulteten.
    Haapaniemi, Staffan
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Kirurgiska kliniken ViN.
    Myrelid, Pär
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Kirurgiska kliniken US.
    Stange, Eduard F
    Department of Gastroenterology, Dept. Internal Medicine I, University of Tübingen, 72076 Tübingen, Germany.
    Söderholm, Johan D
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Kirurgiska kliniken US.
    Keita, Åsa
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten.
    Antagonism of Adherent Invasive E. coli LF82 With Human α-defensin 5 in the Follicle-associated Epithelium of Patients With Ileal Crohn’s Disease2021Ingår i: Inflammatory Bowel Diseases, ISSN 1078-0998, E-ISSN 1536-4844, Vol. 27, nr 7, s. 1116-1127Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: The first visible signs of Crohns disease (CD) are microscopic erosions over the follicle-associated epithelium (FAE). The aim of the study was to investigate the effects of human alpha-defensin 5 (HD5) on adherent-invasive Escherichia coli LF82 translocation and HD5 secretion after LF82 exposure in an in vitro model of human FAE and in human FAE ex vivo. Methods: An in vitro FAE-model was set up by the coculture of Raji B cells and Caco-2-cl1 cells. Ileal FAE from patients with CD and controls were mounted in Ussing chambers. The effect of HD5 on LF82 translocation was studied by LF82 exposure to the cells or tissues with or without incubation with HD5. The HD5 secretion was measured in human FAE exposed to LF82 or Salmonella typhimurium. The HD5 levels were evaluated by immunofluorescence, immunoblotting, and ELISA. Results: There was an increased LF82 translocation across the FAE-model compared with Caco-2-cl1 (P < 0.05). Incubation of cell/tissues with HD5 before LF82 exposure reduced bacterial passage in both models. Human FAE showed increased LF82 translocation in CD compared with controls and attenuated passage after incubation with sublethal HD5 in both CD and controls (P < 0.05). LF82 exposure resulted in a lower HD5 secretion in CD FAE compared with controls (P < 0.05), whereas Salmonella exposure caused equal secretion on CD and controls. There were significantly lower HD5 levels in CD tissues compared with controls. Conclusions: Sublethal HD5 reduces the ability of LF82 to translocate through FAE. The HD5 is secreted less in CD in response to LF82, despite a normal response to Salmonella. This further implicates the integrated role of antimicrobial factors and barrier function in CD pathogenesis.

  • 95.
    Allorto, Nikki
    et al.
    Univ KwaZulu Natal, South Africa.
    Rencken, Camerin A.
    Brown Univ, RI USA.
    Wall, Shelley
    Univ KwaZulu Natal, South Africa; Univ KwaZulu Natal, South Africa.
    Pompermaier, Laura
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Hand- och plastikkirurgiska kliniken US.
    Factors impacting time to surgery and the effect on in-hospital mortality2021Ingår i: Burns, ISSN 0305-4179, E-ISSN 1879-1409, Vol. 47, nr 4, s. 922-929Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objectives: Early surgery improves outcomes after burn injuries but is often not available in limited resource settings (LRS), where a more conservative approach is widespread. This study aimed to analyze factors associated with delay in surgical treatment, and the impact on in-hospital mortality. Methods: All patients with burns treated with surgery between 2016 and 2019 at the Pietermaritzburg Burn Service, in South Africa, were included in this retrospective study. Early surgery was defined as patients who underwent surgery within 7 days from injury. The population was analyzed descriptively and differences between groups were tested using t-test, and chi(2) test or Fishers exact test, as appropriate. Multivariable logistic regression was used to analyze the effect of delay in surgical treatment on in-hospital mortality, after adjustment for confounders. Results: During the study period, 620 patients with burns underwent surgery. Of them, 16% had early surgery. The early surgery group had a median age and TBSA of 11 years (3-35) and 12.0% (5-22) compared to 7 years (2-32) and 6.0% (3-13) in the late surgery group (p=0.45, p&lt;0.001). In logistic regression, female sex [aOR: 3.30 (95% CI: 1.47-7.41)], TBSA% [aOR: 1.09 (95% CI: 1.05-1.12)], and FTB [aOR: 3.21 (95% CI: 1.43-7.18)] were associated with in-hospital mortality, whereas having early surgery was not [aOR: 1.74 (95% CI: 0.76-3.98)]. Conclusion: This study found that early surgery was not associated with in-hospital mortality. Independent predictors of in-hospital mortality were female sex, presence of full thickness burn, and larger burn size. Future studies should investigate if burn care capacity in LRS may influence the association between early excision and outcome. (C) 2020 Elsevier Ltd and ISBI. All rights reserved.

  • 96.
    Alm Mårtensson, Anna
    et al.
    Länsstyrelsen i Jönköping, Sverige.
    Boström, Anita
    Institutionen för hälsovetenskaper, Karlstads universitet, Sverige.
    Lindmark, Ulrika
    Jönköping University, HHJ, Avd. för naturvetenskap och biomedicin, Sverige.
    Lundgren, Charlie
    Länsstyrelsen Västerbotten, Sverige.
    Ludvigsson, Mikael
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Centrum för social och affektiv neurovetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Psykiatricentrum, Psykiatriska kliniken i Linköping. Region Östergötland, Närsjukvården i centrala Östergötland, Medicinska och geriatriska akutkliniken. Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för prevention, rehabilitering och nära vård.
    Simmons, Johanna
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för prevention, rehabilitering och nära vård. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Närsjukvården i centrala Östergötland, Medicinska och geriatriska akutkliniken.
    Att möta våldsutsatta äldre personer2022Ingår i: Äldre personers utsatthet för våld i nära relationer: Interprofessionella perspektiv / [ed] Lena Östlund, Lund: Studentlitteratur AB , 2022, s. 183-220Kapitel i bok, del av antologi (Övrigt vetenskapligt)
  • 97.
    Almeida, Joana R.
    et al.
    Univ Porto, Portugal.
    Palmeira, Andreia
    Univ Porto, Portugal.
    Campos, Alexandre
    Univ Porto, Portugal.
    Cunha, Isabel
    Univ Porto, Portugal.
    Freitas, Micaela
    Univ Porto, Portugal; Univ Geneva, Switzerland.
    Felpeto, Aldo Barreiro
    Univ Porto, Portugal.
    Turkina, Maria V
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för neurobiologi. Linköpings universitet, Medicinska fakulteten.
    Vasconcelos, Vitor
    Univ Porto, Portugal.
    Pinto, Madalena
    Univ Porto, Portugal.
    Correia-da-Silva, Marta
    Univ Porto, Portugal.
    Sousa, Emilia
    Univ Porto, Portugal.
    Structure-Antifouling Activity Relationship and Molecular Targets of Bio-Inspired(thio)xanthones2020Ingår i: Biomolecules, E-ISSN 2218-273X, Vol. 10, nr 8, artikel-id 1126Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The development of alternative ecological and effective antifouling technologies is still challenging. Synthesis of nature-inspired compounds has been exploited, given the potential to assure commercial supplies of potential ecofriendly antifouling agents. In this direction, the antifouling activity of a series of nineteen synthetic small molecules, with chemical similarities with natural products, were exploited in this work. Six (4,5,7,10,15and17) of the tested xanthones showed in vivo activity toward the settlement ofMytilus galloprovincialislarvae (EC50: 3.53-28.60 mu M) and low toxicity to this macrofouling species (LC50&gt; 500 mu M and LC50/EC50: 17.42-141.64), and two of them (7and10) showed no general marine ecotoxicity (Artemia salinamortality) after 48 h of exposure. Regarding the mechanism of action in mussel larvae, the best performance compounds4and5might be acting by the inhibition of acetylcholinesterase activity (in vitro and in silico studies), while7and10showed specific targets (proteomic studies) directly related with the mussel adhesive structure (byssal threads), given by the alterations in the expression ofMytiluscollagen proteins (PreCols) and proximal thread proteins (TMPs). A quantitative structure-activity relationship (QSAR) model was built with predictive capacity to enable speeding the design of new potential active compounds.

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  • 98.
    Almeland, Stian Kreken
    et al.
    Haukeland Hosp, Norway; Univ Bergen, Norway; Norwegian Directorate Hlth, Norway.
    Depoortere, Evelyn
    European Commiss, Belgium.
    Jennes, Serge
    Grand Hop Charleroi, Belgium.
    Sjöberg, Folke
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Hand- och plastikkirurgiska kliniken US.
    Basanta, J. Alfonso Lozano
    European Commiss, Belgium.
    Zanatta, Sofia
    European Commiss, Belgium.
    Alexandru, Calin
    Minist Internal Affairs, Romania.
    Ramon Martinez-Mendez, Jose
    Hosp Univ La Paz, Spain.
    van der Vlies, Cornelis H.
    Maasstad Hosp, Netherlands; Erasmus MC, Netherlands.
    Hughes, Amy
    Int Network Training Educ & Res Burns, Wales; Barts Hlth NHS Trust, England; Essex & Herts Air Ambulance Charitable Trust, England.
    Barret, Juan P.
    Univ Autonoma Barcelona, Spain.
    Moiemen, Naiem
    Univ Hosp Birmingham Fdn Trust, England; Univ Birmingham, England.
    Leclerc, Thomas
    Percy Mil Teaching Hosp, France.
    Burn mass casualty incidents in Europe: A European response plan within the European Union Civil Protection Mechanism2022Ingår i: Burns, ISSN 0305-4179, E-ISSN 1879-1409, Vol. 48, nr 8, s. 1794-1804Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Burn care is centralized in highly specialized burn centers in Europe. These centers are of limited capacity and may be overwhelmed by a sudden surge in case of a burn mass casualty incident. Prior incidents in Europe and abroad have sustained high standards of care through well-orchestrated responses to share the burden of care in several burn centers. A burn mass casualty incident in Romania in 2015 sparked an initiative to strengthen the existing EU mechanisms. This paper aims to provide insight into developing a response plan for burn mass casualties within the EU Civil Protection Mechanism. Methods: The European Burns Association drafted medical guidelines for burn mass casualty incidents based on a literature review and an in-depth analysis of the Romanian incident. An online questionnaire surveyed European burn centers and EU States for burn mass casualty preparedness. Results: The Romanian burn mass casualty in 2015 highlighted the lack of a burn-specific mechanism, leading to the late onset of international transfers. In Europe, 71% of respondents had existing mass casualty response plans, though only 35% reported having a burn-specific plan. A burns response plan for burn mass casualties was developed and adopted as a Commission staff working document in preparation for further implementation. The plan builds on the existing Union Civil Protection Mechanism framework and the standards of the WHO Emergency Medical Teams initiative to provide 1) burn assessment teams for specialized in-hospital triage of patients, 2) specialized burn care across European burn centers, and 3) medevac capacities from participating states. Conclusion: The European burn mass casualty response plan could enable the delivery of high-level burn care in the face of an overwhelming incident in an affected European country. Further steps for integration and implementation of the plan within the Union Civil Protection Mechanism framework are needed.

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  • 99.
    Almlöv, Karin
    et al.
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Kirurgiska kliniken ViN.
    Woisetschläger, Mischa
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för diagnostik och specialistmedicin. Region Östergötland, Diagnostikcentrum, Röntgenkliniken i Linköping. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV. Linköpings universitet, Medicinska fakulteten.
    Loftås, Per
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Kirurgiska kliniken US.
    Hallböök, Olof
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Kirurgiska kliniken US.
    Elander, Nils
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Sandström, Per
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Kirurgiska kliniken US.
    MRI Lymph Node Evaluation for Prediction of Metastases in Rectal Cancer2020Ingår i: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 40, nr 5, s. 2757-2763Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Aim: To explore whether the size and characteristics of the largest regional lymph node in patients with rectal cancer, based on magnetic resonance imaging (MRI), following neoadjuvant therapy and before surgery, is able to identify patients at high risk of developing metachronous metastases.

    Patients and Methods: A retrospective case–control study with data from the Swedish Colo-Rectal Cancer Registry. Forty patients were identified with metachronous metastases (M+), and 40 patients without metastases (M0) were matched as controls.

    Results: Patients with M+ disease were more likely to have a regional lymph node measuring ≥5 mm than patients with M0. (87% vs. 65%, p=0.02). There was also a significant difference between the groups regarding the presence of an irregular border of the largest lymph node (68% vs. 40%, p=0.01).

    Conclusion: Lymph nodes measuring ≥5 mm with/without displaying irregular borders at MRI performed after neoadjuvant therapy emerged as risk factors for metachronous metastases in patients with rectal cancer. Intensified follow-up programmes may be indicated in these patients.

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  • 100.
    Al-Motlaq, Mohammad
    et al.
    Hashemite Univ, Jordan.
    Neill, Sarah
    Univ Plymouth, England.
    Foster, Mandie Jane
    Edith Cowan Univ, Australia; Perth Childrens Hosp, Australia.
    Coyne, Imelda
    Trinity Coll Dublin, Ireland; Trinity Coll Dublin, Ireland.
    Houghton, Davina
    Edith Cowan Univ, Australia.
    Angelhoff, Charlotte
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Barn- och kvinnocentrum, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Rising-Holmstrom, Malin
    Mid Sweden Univ, Sweden.
    Majamanda, Maureen
    Univ Malawi, Malawi; Consortium Adv Training Africa CARTA, Kenya.
    Position statement of the international network for child and family centered care: Child and family centred care during the COVID19 pandemic2021Ingår i: Journal of Pediatric Nursing: Nursing Care of Children and Families, ISSN 0882-5963, E-ISSN 1532-8449, Vol. 61, s. 140-143Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    It is the position of the International Network for Child and Family Centered Care (INCFCC) that COVID-19 restrictions pose tremendous challenges for the health care team in their efforts to provide child and family centered care (CFCC). COVID-19 restrictions impact on the familys right to be presernt with their ill child and to contribute to the caring process. A limited number of articles have discussed challenges about the successful delivery of CFCC during the COVID-19 pandemic. Based on current literature, the INCFCC stresses the need for continuous facilitation implementation of child and family centred care as, it is essential for childrens physical and psychological wellbeing. Furthermore we believe that the families presence and participation holds more benefits than risks to the health of children, their families, and the health care team. (C) 2021 Elsevier Inc. All rights reserved.

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