Publikationer från Uppsala Universitet
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Immune Characterization of a Vietnamese Cohort With Idiopathic Inflammatory Myopathies
No full textIntroduction/AimsIdiopathic inflammatory myopathies (IIMs) are classified into five subtypes that are associated with distinct groups of myositis-specific antibodies (MSAs). Variations in the prevalence, genetic predisposition and clinical manifestations exist in patients with IIM from different ethnic backgrounds. In this study, we aimed to characterize the immunopathological changes in muscle tissue and serum cytokines in a Vietnamese IIM cohort with Kinh ethnicity. Methods Muscle biopsies, sera, clinical data, and autoantibody profiles from 64 patients with IIM were included. Muscles were stained by immunohistochemistry using antibodies that target immune cells and molecules. Serum cytokines were measured by multiplex bead arrays. Clustering analysis was performed using the partitioning around medoids algorithm. Results The anti-MDA5 antibody was the most common MSA in this cohort (15.6%), followed by anti-Jo-1 (10.9%). A wide range of clinical manifestations and immunohistological features were seen within the serologically defined subgroups. There was no difference in the levels of immune cells, capillary density or dilation, or patterns of C5b-9 expression between the myositis subgroups. MHC-I patterns were the only immunomorphological variable that was different in these subgroups. IP-10, IL-17A, and APRIL were increased in patients with IIM compared to healthy controls (p = 5.7 x 10-3, 6.9 x 10-4, 2.4 x 10-3, respectively) but without difference between IIM subgroups. Discussion Vietnamese patients with IIM demonstrated widely varying clinical and immunopathological features, with dermatomyositis and immune-mediated necrotizing myopathy representing opposite ends of MHC-I upregulation in muscle tissue. Thus classification of myositis requires comprehensive evaluation of clinical manifestations, serology profiling and muscle pathology
Validation of the Swedish version of HLS19-Q12 : a measurement for general health literacy
No full textHealth literacy (HL) is a critical determinant of health, as it affects health behavior and outcomes, in addition to equity in health. This study aimed to translate, culturally adapt, and validate the Swedish version of HLS19-Q12 (HLS19-Q12-SE). The HLS19-Q12 is a widely used instrument that consists of 12-items and is often used to assess HL in Europe. A convergent mixed-methods design was applied, including cognitive interviews (n = 8) and psychometric testing with a survey sample (n = 374) and test–retest group (n = 28). The instrument was forward and backwards translated and culturally adapted. Data was analyzed using confirmatory and exploratory factor analysis, correlation testing, and reliability assessments. Cognitive interviews explored the clarity, interpretation, and contextual relevance of the items. Participants found the HLS19-Q12-SE clear and easy to understand, though some reported difficulties with unfamiliar health situations and uncertainty of the term “health information.” Based on the interviews, the examples for one of the items were culturally adapted. Psychometric testing showed good feasibility, no floor or ceiling effects on scale level, and moderate positive correlations with other HL instruments, supporting internal and external validity. Structural validity was confirmed, and internal consistency and test–retest reliability were satisfactory. However, ceiling effects were observed at the dichotomous item level, and correlations with self-rated health and social status were low. The HLS19-Q12-SE is a reliable and valid instrument for assessing general HL in Sweden. While psychometric properties were strong overall, future research should address ceiling effects on item level and explore the instrument’s performance in more diverse populations
Protocolized REDUction of Non‐Resuscitation Fluids in SEptic Shock Patients : A Protocol for the REDUSE Randomized Clinical Trial
No full textIn septic shock, administration of large fluid volumes is associated with poor outcomes. Recent evidence shows that non-resuscitation fluids are the major modifiable source of fluids for patients with septic shock in intensive care units (ICUs). This clinical trial is designed to test the hypothesis that restrictive administration of non-resuscitation fluids improves outcomes compared to usual care. Adult patients admitted to ICUs with septic shock will be randomly assigned within 12 h of admission to receive protocolized restrictive administration of non-resuscitation fluids or usual care. The primary outcome is all-cause mortality at 90 days. Secondary outcomes are complications during ICU stay up to 90 days (defined as any acute kidney injury or cerebral, coronary, intestinal, or limb ischemia), mechanical ventilation free days within 90 days, and for survivors cognitive function (by the Montreal Cognitive Assessment [MOCA-BLIND]) and Health-Related Quality of Life (by the EQ Visual Analogue Scale [EQ-VAS]), both at 6 months. In addition, the climate impact of the interventions will be assessed. To detect an absolute reduction in mortality of 7.5%, with an alpha of 5% and a power of 90%, we aim to include 1850 patients. The trial is approved by the Swedish Ethical Review Authority. Results of primary and secondary clinical outcomes and the environmental outcome will be submitted for publication in a peer-reviewed journal. Trial Registration: NCT06140147
Parallel within-host evolution alters virulence factors in an opportunistic Klebsiella pneumoniae during a hospital outbreak
No full textBacterial pathogens adapt to host niches because of selective within-host pressures, an evolutionary process that offers invaluable insights into host-pathogen interactions. Here, we retrospectively track the evolution of a single multiresistant Klebsiella pneumoniae clone in 110 patients over a 5-year nosocomial outbreak. We combine comparative genomics with phenotypic characterization of mucoviscosity, serum survival, iron utilization, biofilm formation, and infection potential in Galleria mellonella for all isolates. Strong positive selection within patients targeted key virulence factors. Notably, convergent evolutionary trajectories were dominated by reduced acute virulence and recurrent changes in iron uptake regulation, capsule and lipopolysaccharide, and enhanced biofilm formation. These phenotypic changes likely represent clinical niche adaptations, with some resulting in trade-offs during gastrointestinal colonization. This study underscores the dynamic nature of within-host evolution and its role in shaping virulence in opportunistic pathogens, even on short time scales
How educational leaders in Sweden address interculturalism : a systematic literature review and an illustrative case
No full textThis article presents a systematic literature review to analyse the knowledge contributions of research in Sweden as to how educational leaders are addressing interculturalism in schools. In total 18 articles were analysed. Besides that, an educational leader was interviewed to enrich the findings from the literature with the experiences of an educational leader who addressed interculturalism from a particular perspective a time when there was an influx of migrants into Sweden. Bronfenbrenner’s [(1979). The ecology of human development: Experiments by nature and design. Harvard University Press] ecological theory was used as a conceptual framework. A major shortcoming in the research field on interculturalism is that there is little literature on how educational leaders in Sweden approach it. Furthermore, the research contributes with knowledge mostly about what hinders interculturalism and about the macrosystem. The findings of this article aim to explore these lacunae and provide suggestions on how to address interculturalism. The results are discussed in relation to needs for future research
Pyrophosphate-Containing Calcium Phosphates Negatively Impact Heterotopic Bone Quality
No full textIn bone, critical size defects pose substantial challenge in maxillofacial and orthopedic reconstructions as they are incapable of spontaneous regeneration. In such cases, autografts, allografts, and bone graft substitutes are used. Calcium phosphates (CaP) are widely used bone graft substitutes due to their biocompatibility, osteoconductive properties, and potential for osteoinductivity. CaP materials containing monetite, beta-tricalcium phosphate (beta-TCP), and a small amount of calcium pyrophosphate (Ca-PP) possess both osteoconductive and osteoinductive properties. However, the role of Ca-PP in osteoinduction and material degradation remains unexplored. This study investigates heterotopic bone formation in response to five CaP compositions, maintaining a constant monetite to beta-TCP ratio, with varying amounts of Ca-PP (0-12.5%). Twelve adult female sheep (Ovis aries) are subcutaneously implanted with constructs made of six CaP tiles interconnected by a Ti6Al4V frame and a control implant. Histological analysis, backscattered electron scanning electron microscopy, and Raman spectroscopy of samples retrieved at 12- and 52 weeks reveal that Ca-PP does not hinder heterotopic bone formation and minimally impacts CaP degradation. While monetite and beta-TCP transform into apatite, the Ca-PP phase remains unchanged. The addition of Ca-PP to the CaP influences heterotopic bone quality and inflammatory response during tissue regeneration
Frequent Hybridisation Between Parapatric Lekking Bird-of-Paradise Species
No full textHybridisation is known to occur between a wide range of taxa, including species for which strong sexual selection has led to markedly different sexual phenotypes and lek-mating behaviours. To what extent occasional hybridisation can overcome the reproductive barriers in such systems and, for example, lead to the establishment of hybrid zones is poorly known. In this study, we address this question by focusing on one of the most well-known avian radiations in which sexual selection has resulted in an extraordinary assemblage of phenotypic diversity and lek-mating behaviours: the birds-of-paradise (Paradisaeidae). We quantify the genome-wide distribution of introgression and find multiple signals of recent and historical gene flow between and within two genera of birds-of-paradise, Astrapia and Paradigalla. In addition, we present the first empirical genomic indication of a putative hybrid zone between two lekking bird-of-paradise species that differ substantially in their sexually selected traits and behaviours. Our findings are consistent with the idea that behavioural and phenotypic traits may constitute weaker pre- and post-zygotic barriers to gene flow than generally thought in lek-mating species
AI supported diagnostic innovations for impact in global women's health
No full textNina Linder and colleagues examine how artificial intelligence could be applied to diagnostic methods that rely on highly trained experts, such as cytological screening for cervical cancer, enabling implementation even in resource limited setting
In Vitro Elimination of Highly Multidrug-Resistant Bacteria by the Lactic Acid Bacterial Drug Candidate ILP100
No full textIntroduction: Multidrug resistance (MDR) has been identified in wound bacterial isolates from Ukrainian war victims treated in Ukraine and across Europe. ILP100, a drug candidate for the treatment of skin wounds, is composed of a Limosilactobacillus reuteri expressing human chemokine CXCL12. In this study, the antimicrobial effects of ILP100 were tested on MDR bacteria isolated from wounds of Ukrainian war victims. Methods: ILP100 was co-cultured with one of the wound pathogens (Pseudomonas aeruginosa, Acinetobacter baumannii, Enterobacter cloacae, Klebsiella pneumoniae, Proteus mirabilis, Staphylococcus aureus; 12 non-MDR and 12 MDR isolates) in broth media for 12 h with subsequent survival recovery on agar plates. Additionally, agar plates were precoated with ILP100 at clinical doses (3 vs. 24 h, 1 x 10(7) CFU/cm(2)) followed by co-culture with pathogens inoculated in soft agar (1 x 10(4 )CFU/cm(2)). To compare ILP100 with relevant antibiotics, MDR-inoculated soft agar was applied to plates with standardized ILP100 drops and antibiotic-loaded discs, followed by 18-20 h aerobic incubation at 37 degrees C. Results: Dose-dependent growth inhibition of all pathogens was demonstrated, as 1000:1 and 100:1 (ILP100/isolate) inhibited pathogenic growth up to log 6.4 and log 4.3 CFU/ml, respectively. Potent antimicrobial effects were demonstrated after precoating with ILP100, as pathogen recovery was only demonstrated after 3 h of precoating, only for 10/18 isolates and then only partially. Benchmarking to relevant antibiotic discs resulted in large cleared zones surrounding the ILP100 spots but not the antibiotic discs, demonstrating potent bacterial killing by ILP100-secreted factors. Interestingly, the MDR pathogens were significantly more sensitive to the ILP100 released factors than the non-MDR isolates. Conclusion: ILP100 effectively eliminates MDR wound pathogens, which reveals a promising strategy for the development of new classes of urgently needed antimicrobials
