| 1. |
- Klingspor, L., et al.
(författare)
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Epidemiology of fungaemia in Sweden: A nationwide retrospective observational survey
- 2018
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Ingår i: Mycoses. - : Wiley. - 0933-7407 .- 1439-0507. ; 61:10, s. 777-785
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Tidskriftsartikel (refereegranskat)abstract
- ObjectivesTo identify the epidemiology and antifungal susceptibilities of Candida spp. among blood culture isolates to identify the epidemiology and antifungal susceptibilities of Candida spp. among blood culture isolates in Sweden. MethodsThe study was a retrospective, observational nationwide laboratory-based surveillance for fungaemia and fungal meningitis and was conducted from September 2015 to August 2016. ResultsIn total, 488 Candida blood culture isolates were obtained from 471 patients (58% males). Compared to our previous study, the incidence of candidaemia has increased from 4.2/100000 (2005-2006) to 4.7/100000 population/year (2015-2016). The three most common Candida spp. isolated from blood cultures were Candida albicans (54.7%), Candida glabrata (19.7%) and species in the Candida parapsilosis complex (9.4%). Candida resistance to fluconazole was 2% in C.albicans and between 0% and 100%, in non-albicans species other than C.glabrata and C.krusei. Resistance to voriconazole was rare, except for C.glabrata, C.krusei and C.tropicalis. Resistance to anidulafungin was 3.8% while no Candida isolate was resistant to amphotericin B. ConclusionsWe report an overall increase in candidaemia but a minor decrease of C.albicans while C.glabrata and C.parapsilosis remain constant over this 10-year period.
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| 2. |
- Lindqvist, Maria, et al.
(författare)
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Long-term persistence of a multi-resistant methicillin-susceptible Staphylococcus aureus (MR-MSSA) clone at a university hospital in southeast Sweden, without further transmission within the region
- 2015
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Ingår i: European Journal of Clinical Microbiology and Infectious Diseases. - : Springer Verlag (Germany). - 0934-9723 .- 1435-4373. ; 34:7, s. 1415-1422
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Tidskriftsartikel (refereegranskat)abstract
- The objective of this study was to characterise isolates of methicillin-susceptible Staphylococcus aureus (MSSA) with resistance to clindamycin and/or tobramycin in southeast Sweden, including the previously described ECT-R clone (t002) found in Östergotland County, focusing on clonal relatedness, virulence determinants and existence of staphylococcal cassette chromosome (SCC) mec remnants. MSSA isolates with resistance to clindamycin and/or tobramycin were collected from the three county councils in southeast Sweden and investigated with spa typing, polymerase chain reaction (PCR) targeting the SCCmec right extremity junction (MREJ) and DNA microarray technology. The 98 isolates were divided into 40 spa types, and by microarray clustered in 17 multi-locus sequence typing (MLST) clonal complexes (MLST-CCs). All isolates with combined resistance to clindamycin and tobramycin (n = 12) from Östergotland County and two additional isolates (clindamycin-R) were designated as spa type t002, MREJ type ii and were clustered in CC5, together with a representative isolate of the ECT-R clone, indicating the clones persistence. These isolates also carried several genes encoding exotoxins, Q9XB68-dcs and qacC. Of the isolates in CC15, 83 % (25/30) were tobramycin-resistant and were designated spa type t084. Of these, 68 % (17/25) were isolated from new-borns in all three counties. The persistence of the ECT-R clone in Östergotland County, although not found in any other county in the region, carrying certain virulence factors that possibly enhance its survival in the hospital environment, highlights the fact that basic hygiene guidelines must be maintained even when MRSA prevalence is low.
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| 3. |
- Beal, Jacob, et al.
(författare)
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Robust estimation of bacterial cell count from optical density
- 2020
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Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
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Tidskriftsartikel (refereegranskat)abstract
- Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
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| 4. |
- Boza-Serrano, Antonio, et al.
(författare)
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Galectin-3, a novel endogenous TREM2 ligand, detrimentally regulates inflammatory response in Alzheimer’s disease
- 2019
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Ingår i: Acta Neuropathologica. - : Springer Science and Business Media LLC. - 0001-6322 .- 1432-0533. ; 138:2, s. 251-273
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Tidskriftsartikel (refereegranskat)abstract
- Alzheimer’s disease (AD) is a progressive neurodegenerative disease in which the formation of extracellular aggregates of amyloid beta (Aβ) peptide, fibrillary tangles of intraneuronal tau and microglial activation are major pathological hallmarks. One of the key molecules involved in microglial activation is galectin-3 (gal3), and we demonstrate here for the first time a key role of gal3 in AD pathology. Gal3 was highly upregulated in the brains of AD patients and 5xFAD (familial Alzheimer’s disease) mice and found specifically expressed in microglia associated with Aβ plaques. Single-nucleotide polymorphisms in the LGALS3 gene, which encodes gal3, were associated with an increased risk of AD. Gal3 deletion in 5xFAD mice attenuated microglia-associated immune responses, particularly those associated with TLR and TREM2/DAP12 signaling. In vitro data revealed that gal3 was required to fully activate microglia in response to fibrillar Aβ. Gal3 deletion decreased the Aβ burden in 5xFAD mice and improved cognitive behavior. Interestingly, a single intrahippocampal injection of gal3 along with Aβ monomers in WT mice was sufficient to induce the formation of long-lasting (2 months) insoluble Aβ aggregates, which were absent when gal3 was lacking. High-resolution microscopy (stochastic optical reconstruction microscopy) demonstrated close colocalization of gal3 and TREM2 in microglial processes, and a direct interaction was shown by a fluorescence anisotropy assay involving the gal3 carbohydrate recognition domain. Furthermore, gal3 was shown to stimulate TREM2–DAP12 signaling in a reporter cell line. Overall, our data support the view that gal3 inhibition may be a potential pharmacological approach to counteract AD.
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| 5. |
- Egevad, L, et al.
(författare)
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Identification of areas of grading difficulties in prostate cancer and comparison with artificial intelligence assisted grading
- 2020
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Ingår i: Virchows Archiv : an international journal of pathology. - : Springer Science and Business Media LLC. - 1432-2307. ; 477:6, s. 777-786
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Tidskriftsartikel (refereegranskat)abstract
- The International Society of Urological Pathology (ISUP) hosts a reference image database supervised by experts with the purpose of establishing an international standard in prostate cancer grading. Here, we aimed to identify areas of grading difficulties and compare the results with those obtained from an artificial intelligence system trained in grading. In a series of 87 needle biopsies of cancers selected to include problematic cases, experts failed to reach a 2/3 consensus in 41.4% (36/87). Among consensus and non-consensus cases, the weighted kappa was 0.77 (range 0.68–0.84) and 0.50 (range 0.40–0.57), respectively. Among the non-consensus cases, four main causes of disagreement were identified: the distinction between Gleason score 3 + 3 with tangential cutting artifacts vs. Gleason score 3 + 4 with poorly formed or fused glands (13 cases), Gleason score 3 + 4 vs. 4 + 3 (7 cases), Gleason score 4 + 3 vs. 4 + 4 (8 cases) and the identification of a small component of Gleason pattern 5 (6 cases). The AI system obtained a weighted kappa value of 0.53 among the non-consensus cases, placing it as the observer with the sixth best reproducibility out of a total of 24. AI may serve as a decision support and decrease inter-observer variability by its ability to make consistent decisions. The grading of these cancer patterns that best predicts outcome and guides treatment warrants further clinical and genetic studies. Results of such investigations should be used to improve calibration of AI systems.
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| 6. |
- Gyllenberg, A, et al.
(författare)
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Age-dependent variation of genotypes in MHC II transactivator gene (CIITA) in controls and association to type 1 diabetes
- 2012
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Ingår i: Genes and Immunity. - Stockholm : Springer Science and Business Media LLC. - 1476-5470 .- 1466-4879. ; 76:2, s. 202-203
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Tidskriftsartikel (refereegranskat)abstract
- The major histocompatibility complex class II transactivator (CIITA) gene (16p13) has been reported to associate with susceptibility to multiple sclerosis, rheumatoid arthritis and myocardial infarction, recently also to celiac disease at genome-wide level. However, attempts to replicate association have been inconclusive. Previously, we have observed linkage to the CIITA region in Scandinavian type 1 diabetes (T1D) families. Here we analyze five Swedish T1D cohorts and a combined control material from previous studies of CIITA. We investigate how the genotype distribution within the CIITA gene varies depending on age, and the association to T1D. Unexpectedly, we find a significant difference in the genotype distribution for markers in CIITA (rs11074932, P=4 × 10(-5) and rs3087456, P=0.05) with respect to age, in the collected control material. This observation is replicated in an independent cohort material of about 2000 individuals (P=0.006, P=0.007). We also detect association to T1D for both markers, rs11074932 (P=0.004) and rs3087456 (P=0.001), after adjusting for age at sampling. The association remains independent of the adjacent T1D risk gene CLEC16A. Our results indicate an age-dependent variation in CIITA allele frequencies, a finding of relevance for the contrasting outcomes of previously published association studies.
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| 7. |
- Malmvall, Bo-Erik, et al.
(författare)
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Reduction of antibiotics sales and sustained low incidence of bacterial resistance : report on a broad approach during 10 years to implement evidence-based indications for antibiotic prescribing in Jönköping County, Sweden
- 2007
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Ingår i: Quality Management in Health Care. - 1063-8628 .- 1550-5154. ; 16:1, s. 60-67
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Tidskriftsartikel (refereegranskat)abstract
- Background: Increased prevalence of resistance in major pathogens decreases the possibility to treat common infectious conditions. In the beginning of the 1990s, resistant pneumococci spread among children in southern Sweden, which alarmed both the profession and the medical authorities. We describe the measures taken to curb the spread of resistance and to reduce the use of antibiotics in outpatient care.Method: A national organization, Strama (Swedish Strategic Programme for the Rational Use of Antimicrobial Agents and Surveillance of Resistance), was initiated in 1994 and a regional committee was formed in Jönköping County in 1995. A multifaceted program was started aiming at reducing antibiotic use in the county by 25% and that the prevalence of resistant pneumococci should not increase.Results: The efforts by the Jönköping County committee has resulted in a 31% total reduction of the consumption of antibiotic drugs in primary care between 1993 and 2005 and a 50% reduction among children aged 0 to 4 years. There has been no increase in the prevalence of resistant pneumococci or Haemophilus influenzae in the county. The decrease in antibiotic use was greater than the average in Sweden.Conclusion: Our regional efforts have been successful. This has probably been achieved by a sustained strategy including repeated campaigns in the media, information to the profession, implementation of guidelines, and feedback to the profession on data on antibiotic prescribing and resistance. We believe it is of outmost importance not only to inform the profession but also the public on the limited effects of antibiotics in most respiratory tract infections.
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| 8. |
- Puschmann, Andreas, et al.
(författare)
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Heterozygous PINK1 p.G411S increases risk of Parkinson's disease via a dominant-negative mechanism
- 2017
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Ingår i: Brain. - : Oxford University Press (OUP). - 1460-2156 .- 0006-8950. ; 140:1, s. 98-117
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Tidskriftsartikel (refereegranskat)abstract
- SEE GANDHI AND PLUN-FAVREAU DOI101093/AWW320 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: It has been postulated that heterozygous mutations in recessive Parkinson's genes may increase the risk of developing the disease. In particular, the PTEN-induced putative kinase 1 (PINK1) p.G411S (c.1231G>A, rs45478900) mutation has been reported in families with dominant inheritance patterns of Parkinson's disease, suggesting that it might confer a sizeable disease risk when present on only one allele. We examined families with PINK1 p.G411S and conducted a genetic association study with 2560 patients with Parkinson's disease and 2145 control subjects. Heterozygous PINK1 p.G411S mutations markedly increased Parkinson's disease risk (odds ratio = 2.92, P = 0.032); significance remained when supplementing with results from previous studies on 4437 additional subjects (odds ratio = 2.89, P = 0.027). We analysed primary human skin fibroblasts and induced neurons from heterozygous PINK1 p.G411S carriers compared to PINK1 p.Q456X heterozygotes and PINK1 wild-type controls under endogenous conditions. While cells from PINK1 p.Q456X heterozygotes showed reduced levels of PINK1 protein and decreased initial kinase activity upon mitochondrial damage, stress-response was largely unaffected over time, as expected for a recessive loss-of-function mutation. By contrast, PINK1 p.G411S heterozygotes showed no decrease of PINK1 protein levels but a sustained, significant reduction in kinase activity. Molecular modelling and dynamics simulations as well as multiple functional assays revealed that the p.G411S mutation interferes with ubiquitin phosphorylation by wild-type PINK1 in a heterodimeric complex. This impairs the protective functions of the PINK1/parkin-mediated mitochondrial quality control. Based on genetic and clinical evaluation as well as functional and structural characterization, we established p.G411S as a rare genetic risk factor with a relatively large effect size conferred by a partial dominant-negative function phenotype.
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