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Sökning: WFRF:(Bergström L) > (2015-2019)

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1.
  • Lorenz, M. W., et al. (författare)
  • Carotid Intima-Media Thickness Progression and Risk of Vascular Events in People With Diabetes: Results From the PROG-IMT Collaboration
  • 2015
  • Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 38:10, s. 1921-1929
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVECarotid intima-media thickness (CIMT) is a marker of subclinical organ damage and predicts cardiovascular disease (CVD) events in the general population. It has also been associated with vascular risk in people with diabetes. However, the association of CIMT change in repeated examinations with subsequent CVD events is uncertain, and its use as a surrogate end point in clinical trials is controversial. We aimed at determining the relation of CIMT change to CVD events in people with diabetes.RESEARCH DESIGN AND METHODSIn a comprehensive meta-analysis of individual participant data, we collated data from 3,902 adults (age 33-92 years) with type 2 diabetes from 21 population-based cohorts. We calculated the hazard ratio (HR) per standard deviation (SD) difference in mean common carotid artery intima-media thickness (CCA-IMT) or in CCA-IMT progression, both calculated from two examinations on average 3.6 years apart, for each cohort, and combined the estimates with random-effects meta-analysis.RESULTSAverage mean CCA-IMT ranged from 0.72 to 0.97 mm across cohorts in people with diabetes. The HR of CVD events was 1.22 (95% CI 1.12-1.33) per SD difference in mean CCA-IMT, after adjustment for age, sex, and cardiometabolic risk factors. Average mean CCA-IMT progression in people with diabetes ranged between -0.09 and 0.04 mm/year. The HR per SD difference in mean CCA-IMT progression was 0.99 (0.91-1.08).CONCLUSIONSDespite reproducing the association between CIMT level and vascular risk in subjects with diabetes, we did not find an association between CIMT change and vascular risk. These results do not support the use of CIMT progression as a surrogate end point in clinical trials in people with diabetes.
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2.
  • Lorenz, M. W., et al. (författare)
  • Predictive value for cardiovascular events of common carotid intima media thickness and its rate of change in individuals at high cardiovascular risk - Results from the PROG-IMT collaboration
  • 2018
  • Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 13:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims Carotid intima media thickness (CIMT) predicts cardiovascular (CVD) events, but the predictive value of CIMT change is debated. We assessed the relation between CIMT change and events in individuals at high cardiovascular risk. From 31 cohorts with two CIMT scans (total n = 89070) on average 3.6 years apart and clinical follow-up, subcohorts were drawn: (A) individuals with at least 3 cardiovascular risk factors without previous CVD events, (B) individuals with carotid plaques without previous CVD events, and (C) individuals with previous CVD events. Cox regression models were fit to estimate the hazard ratio (HR) of the combined endpoint (myocardial infarction, stroke or vascular death) per standard deviation (SD) of CIMT change, adjusted for CVD risk factors. These HRs were pooled across studies. In groups A, B and C we observed 3483, 2845 and 1165 endpoint events, respectively. Average common CIMT was 0.79mm (SD 0.16mm), and annual common CIMT change was 0.01mm (SD 0.07mm), both in group A. The pooled HR per SD of annual common CIMT change (0.02 to 0.43mm) was 0.99 (95% confidence interval: 0.95-1.02) in group A, 0.98 (0.93-1.04) in group B, and 0.95 (0.89-1.04) in group C. The HR per SD of common CIMT (average of the first and the second CIMT scan, 0.09 to 0.75mm) was 1.15 (1.07-1.23) in group A, 1.13 (1.05-1.22) in group B, and 1.12 (1.05-1.20) in group C. We confirm that common CIMT is associated with future CVD events in individuals at high risk. CIMT change does not relate to future event risk in high-risk individuals.
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3.
  • van der Valk, Ralf J P, et al. (författare)
  • A novel common variant in DCST2 is associated with length in early life and height in adulthood.
  • 2015
  • Ingår i: Human molecular genetics. - : Oxford University Press (OUP). - 1460-2083 .- 0964-6906. ; 24:4, s. 1155-68
  • Tidskriftsartikel (refereegranskat)abstract
    • Common genetic variants have been identified for adult height, but not much is known about the genetics of skeletal growth in early life. To identify common genetic variants that influence fetal skeletal growth, we meta-analyzed 22 genome-wide association studies (Stage 1; N = 28 459). We identified seven independent top single nucleotide polymorphisms (SNPs) (P < 1 × 10(-6)) for birth length, of which three were novel and four were in or near loci known to be associated with adult height (LCORL, PTCH1, GPR126 and HMGA2). The three novel SNPs were followed-up in nine replication studies (Stage 2; N = 11 995), with rs905938 in DC-STAMP domain containing 2 (DCST2) genome-wide significantly associated with birth length in a joint analysis (Stages 1 + 2; β = 0.046, SE = 0.008, P = 2.46 × 10(-8), explained variance = 0.05%). Rs905938 was also associated with infant length (N = 28 228; P = 5.54 × 10(-4)) and adult height (N = 127 513; P = 1.45 × 10(-5)). DCST2 is a DC-STAMP-like protein family member and DC-STAMP is an osteoclast cell-fusion regulator. Polygenic scores based on 180 SNPs previously associated with human adult stature explained 0.13% of variance in birth length. The same SNPs explained 2.95% of the variance of infant length. Of the 180 known adult height loci, 11 were genome-wide significantly associated with infant length (SF3B4, LCORL, SPAG17, C6orf173, PTCH1, GDF5, ZNFX1, HHIP, ACAN, HLA locus and HMGA2). This study highlights that common variation in DCST2 influences variation in early growth and adult height.
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4.
  • Liao, X., et al. (författare)
  • Normative values for carotid intima media thickness and its progression: Are they transferrable outside of their cohort of origin?
  • 2016
  • Ingår i: European Journal of Preventive Cardiology. - : Oxford University Press (OUP). - 2047-4873 .- 2047-4881. ; 23:11, s. 1165-1173
  • Tidskriftsartikel (refereegranskat)abstract
    • Background The clinical use of carotid intima media thickness (cIMT) requires normal values, which may be subject to variation of geographical factors, ethnicity or measurement details. The influence of these factors has rarely been studied. The aim of this study was to determine whether normative cIMT values and their association with event risk are generalizable across populations. Design Meta-analysis of individual participant data. Method From 22 general population cohorts from Europe, North America and Asia we selected subjects free of cardiovascular disease. Percentiles of cIMT and cIMT progression were assessed separately for every cohort. Cox proportional hazards models for vascular events were used to estimate hazard ratios for cIMT in each cohort. The estimates were pooled across Europe, North America and Asia, with random effects meta-analysis. The influence of geography, ethnicity and ultrasound protocols on cIMT values and on the hazard ratios was examined by meta-regression. Results Geographical factors, ethnicity and the ultrasound protocol had influence neither on the percentiles of cIMT and its progression, nor on the hazard ratios of cIMT for vascular events. Heterogeneity for percentiles of cIMT and cIMT progression was too large to create meaningful normative values. Conclusions The distribution of cIMT values is too heterogeneous to define universal or regional population reference values. CIMT values vary widely between different studies regardless of ethnicity, geographic location and ultrasound protocol. Prediction of vascular events with cIMT values was more consistent across all cohorts, ethnicities and regions. © 2016 European Society of Cardiology.
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5.
  • Ots, R., et al. (författare)
  • Simulating secondary organic aerosol from missing diesel-related intermediate-volatility organic compound emissions during the Clean Air for London (ClearfLo) campaign
  • 2016
  • Ingår i: Atmospheric Chemistry and Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 16:10, s. 6453-6473
  • Tidskriftsartikel (refereegranskat)abstract
    • We present high-resolution (5aEuro-kmaEuro-aEuro parts per thousand x aEuro-5aEuro-km) atmospheric chemical transport model (ACTM) simulations of the impact of newly estimated traffic-related emissions on secondary organic aerosol (SOA) formation over the UK for 2012. Our simulations include additional diesel-related intermediate-volatility organic compound (IVOC) emissions derived directly from comprehensive field measurements at an urban background site in London during the 2012 Clean Air for London (ClearfLo) campaign. Our IVOC emissions are added proportionally to VOC emissions, as opposed to proportionally to primary organic aerosol (POA) as has been done by previous ACTM studies seeking to simulate the effects of these missing emissions. Modelled concentrations are evaluated against hourly and daily measurements of organic aerosol (OA) components derived from aerosol mass spectrometer (AMS) measurements also made during the ClearfLo campaign at three sites in the London area. According to the model simulations, diesel-related IVOCs can explain on average aEuro parts per thousand aEuro-30aEuro-% of the annual SOA in and around London. Furthermore, the 90th percentile of modelled daily SOA concentrations for the whole year is 3.8aEuro-A mu gaEuro-m(-3), constituting a notable addition to total particulate matter. More measurements of these precursors (currently not included in official emissions inventories) is recommended. During the period of concurrent measurements, SOA concentrations at the Detling rural background location east of London were greater than at the central London location. The model shows that this was caused by an intense pollution plume with a strong gradient of imported SOA passing over the rural location. This demonstrates the value of modelling for supporting the interpretation of measurements taken at different sites or for short durations.
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6.
  • Romania, P., et al. (författare)
  • Identification of a Genetic Variation in ERAP1 Aminopeptidase that Prevents Human Cytomegalovirus miR-UL112-5p-Mediated Immunoevasion
  • 2017
  • Ingår i: Cell Reports. - : Elsevier BV. - 2211-1247. ; 20:4, s. 846-853
  • Tidskriftsartikel (refereegranskat)abstract
    • Herein, we demonstrate that HCMV miR-UL112-5p targets ERAP1, thereby inhibiting the processing and presentation of the HCMV pp65495-503 peptide to specific CTLs. In addition, we show that the rs17481334 G variant, naturally occurring in the ERAP1 30 UTR, preserves ERAP1 from miR-UL1125p-mediated degradation. Specifically, HCMV miRUL112-5p binds the 30 UTR of ERAP1 A variant, but not the 30 UTR of ERAP1 G variant, and, accordingly, ERAP1 expression is reduced both at RNA and protein levels only in human fibroblasts homozygous for the A variant. Consistently, HCMV-infected GG fibroblasts were more efficient in trimming viral antigens and being lysed by HCMV-peptide-specific CTLs. Notably, a significantly decreased HCMV seropositivity was detected among GG individuals suffering from multiple sclerosis, a disease model in which HCMV is negatively associated with adultonset disorder. Overall, our results identify a resistance mechanism to HCMV miR-UL112-5p-based immune evasion strategy with potential implications for individual susceptibility to infection and other diseases.
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7.
  • Bergström, Gunnar, et al. (författare)
  • Preventing sickness absenteeism among employees with common mental disorders or stress-related symptoms at work : Design of a cluster randomized controlled trial of a problem-solving based intervention versus care-as-usual conducted at the Occupational Health Services
  • 2017
  • Ingår i: BMC Public Health. - : BioMed Central. - 1471-2458. ; 17:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Common mental disorders (CMDs) are among the leading causes of sick leave in Sweden and other OECD countries. They result in suffering for the individual and considerable financial costs for the employer and for society at large. The occupational health service (OHS) can offer interventions in which both the individual and the work situation are taken into account. The aim of this paper is to describe the design of a study evaluating the effectiveness of an intervention given at the OHS to employees with CMDs or stress-related symptoms at work. In addition, intervention fidelity and its relation to the outcome will be assessed in a process analysis.Methods: The study is designed as a cluster randomized trial in which the participating OHS consultants are randomized into either delivering the intervention or performing care as usual. Employees with CMDs or stress-related symptoms at work are recruited consecutively by the OHS consultants. The intervention aims to improve the match between the employee and the job situation. Interviews are held individually with the employee and the nearest supervisor, after which a joint meeting with both the employee and the supervisor takes place. A participatory approach is applied by which the supervisor and the employee are guided by the OHS consultant and encouraged to actively take part in problem solving concerning the work situation. Outcomes will be assessed at baseline and at six and 12 months. A long-term follow-up at 3 years will also be performed. The primary outcome is registered sickness absence during a 1-year period after study inclusion. Secondary outcomes are mental health and work ability. The intervention's cost effectiveness, compared to treatment as usual, both for society and for the employer will be evaluated. A process evaluation by both the OHS consultants and the employee will be carried out.Discussion: The study includes analyses of the effectiveness of the intervention (clinical and economic) as well as an analysis of its implementation at the participating OHSs. Possible methodological challenges such as selection bias and risk of contamination between OHS consultants delivering the experimental condition and consultants giving usual care are discussed.
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8.
  • Brugnara, Y., et al. (författare)
  • A collection of sub-daily pressure and temperature observations for the early instrumental period with a focus on the "year without a summer" 1816
  • 2015
  • Ingår i: Climate of the Past. - : Copernicus GmbH. - 1814-9324 .- 1814-9332. ; 11:8, s. 1027-1047
  • Tidskriftsartikel (refereegranskat)abstract
    • The eruption of Mount Tambora (Indonesia) in April 1815 is the largest documented volcanic eruption in history. It is associated with a large global cooling during the following year, felt particularly in parts of Europe and North America, where the year 1816 became known as the "year without a summer". This paper describes an effort made to collect surface meteorological observations from the early instrumental period, with a focus on the years of and immediately following the eruption (1815–1817). Although the collection aimed in particular at pressure observations, correspondent temperature observations were also recovered. Some of the series had already been described in the literature, but a large part of the data, recently digitised from original weather diaries and contemporary magazines and newspapers, is presented here for the first time. The collection puts together more than 50 sub-daily series from land observatories in Europe and North America and from ships in the tropics. The pressure observations have been corrected for temperature and gravity and reduced to mean sea level. Moreover, an additional statistical correction was applied to take into account common error sources in mercury barometers. To assess the reliability of the corrected data set, the variance in the pressure observations is compared with modern climatologies, and single observations are used for synoptic analyses of three case studies in Europe. All raw observations will be made available to the scientific community in the International Surface Pressure Databank.
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9.
  • Feeney, Orlagh M, et al. (författare)
  • 50 years of oral lipid-based formulations : Provenance, progress and future perspectives
  • 2016
  • Ingår i: Advanced Drug Delivery Reviews. - : Elsevier BV. - 0169-409X .- 1872-8294. ; 101, s. 167-194
  • Forskningsöversikt (refereegranskat)abstract
    • Lipid based formulations (LBF) provide well proven opportunities to enhance the oral absorption of drugs and drug candidates that sit close to, or beyond, the boundaries of Lipinski's 'rule-of-five' chemical space. Advantages in permeability, efflux and pre-systemic metabolism are evident; however, the primary benefit is in increases in dissolution and apparent intestinal solubility for lipophilic, poorly water soluble drugs. This review firstly details the inherent advantages of LBF, their general properties and classification and provides a brief retrospective assessment of the development of LBF over the past fifty years. More detailed analysis of the ability of LBF to promote intestinal solubilisation, supersaturation and absorption is then provided alongside review of the methods employed to assess formulation performance. Critical review of the ability of simple dispersion and more complex in vitro digestion methods to predict formulation performance subsequently reveals marked differences in the correlative ability of in vitro tests, depending on the properties of the drug involved. Notably, for highly permeable low melting drugs e.g. fenofibrate, LBF appear to provide significant benefit in all cases, and sustained on-going solubilisation may not be required. In other cases, and particularly for higher melting point drugs such as danazol, where re-dissolution of crystalline precipitate drug is likely to be slow, correlations with on-going solubilisation and supersaturation are more evident. In spite of their potential benefits, one limitation to broader use of LBF is low drug solubility in the excipients employed to generate formulations. Techniques to increase drug lipophilicity and lipid solubility are therefore explored, and in particular those methods that provide for temporary enhancement including lipophilic ionic liquid and prodrug technologies. The transient nature of these lipophilicity increases enhances lipid solubility and LBF viability, but precludes enduring effects on receptor promiscuity and off target toxicity. Finally, recent efforts to generate solid LBF are briefly described as a means to circumvent the need to encapsulate in soft or hard gelatin capsules, although the latter remain popular with consumers and a proven means of LBF delivery.
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11.
  • Leonov, A. A., et al. (författare)
  • Separation of electrons and protons in the GAMMA-400 gamma-ray telescope
  • 2015
  • Ingår i: Advances in Space Research. - : Elsevier BV. - 0273-1177 .- 1879-1948. ; 56:7, s. 1538-1545
  • Tidskriftsartikel (refereegranskat)abstract
    • The GAMMA-400 telescope will measure the fluxes of gamma rays and cosmic-ray electrons and positrons in the energy range from 100 MeV to several TeV. These measurements will allow it to achieve the following scientific objectives: search for signatures of dark matter, investigation of gamma-ray point-like and extended sources, study of the energy spectrum of the Galactic and extragalactic diffuse emission, study of gamma-ray bursts and gamma-ray emission from the active Sun, together with high-precision measurements of the high-energy electrons and positrons spectra, protons and nuclei up to the knee. The bulk of cosmic rays are protons and helium nuclei, whereas the lepton component in the total flux is similar to 10(-3) at high energy. In the present paper, the simulated capability of the GAMMA-400 telescope to distinguish electrons and positrons from protons in cosmic rays is addressed. The individual contribution to the proton rejection from each detector system of GAMMA-400 is studied separately. The use of the combined information from all detectors allows us to reach a proton rejection of the order of similar to 4 x 10(5) for vertical incident particles and similar to 3 x 10(5) for particles with initial inclination of 30 degrees in the electron energy range from 50 GeV to 1 TeV. (C) 2015 COSPAR.
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12.
  • Willeit, Peter, et al. (författare)
  • Inflammatory markers and extent and progression of early atherosclerosis : Meta-analysis of individual-participant-data from 20 prospective studies of the PROG-IMT collaboration
  • 2016
  • Ingår i: European Journal of Preventive Cardiology. - : Oxford University Press (OUP). - 2047-4873 .- 2047-4881. ; 23:2, s. 194-205
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundLarge-scale epidemiological evidence on the role of inflammation in early atherosclerosis, assessed by carotid ultrasound, is lacking. We aimed to quantify cross-sectional and longitudinal associations of inflammatory markers with common-carotid-artery intima-media thickness (CCA-IMT) in the general population. MethodsInformation on high-sensitivity C-reactive protein, fibrinogen, leucocyte count and CCA-IMT was available in 20 prospective cohort studies of the PROG-IMT collaboration involving 49,097 participants free of pre-existing cardiovascular disease. Estimates of associations were calculated within each study and then combined using random-effects meta-analyses. ResultsMean baseline CCA-IMT amounted to 0.74mm (SD=0.18) and mean CCA-IMT progression over a mean of 3.9 years to 0.011mm/year (SD=0.039). Cross-sectional analyses showed positive linear associations between inflammatory markers and baseline CCA-IMT. After adjustment for traditional cardiovascular risk factors, mean differences in baseline CCA-IMT per one-SD higher inflammatory marker were: 0.0082mm for high-sensitivity C-reactive protein (p<0.001); 0.0072mm for fibrinogen (p<0.001); and 0.0025mm for leucocyte count (p=0.033). Inflammatory load', defined as the number of elevated inflammatory markers (i.e. in upper two quintiles), showed a positive linear association with baseline CCA-IMT (p<0.001). Longitudinal associations of baseline inflammatory markers and changes therein with CCA-IMT progression were null or at most weak. Participants with the highest inflammatory load' had a greater CCA-IMT progression (p=0.015). ConclusionInflammation was independently associated with CCA-IMT cross-sectionally. The lack of clear associations with CCA-IMT progression may be explained by imprecision in its assessment within a limited time period. Our findings for inflammatory load' suggest important combined effects of the three inflammatory markers on early atherosclerosis.
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13.
  • Abdelmagid, N., et al. (författare)
  • Von Willebrand Factor Gene Variants Associate with Herpes simplex Encephalitis
  • 2016
  • Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 11:5
  • Tidskriftsartikel (refereegranskat)abstract
    • Herpes simplex encephalitis (HSE) is a rare complication of Herpes simplex virus type-1 infection. It results in severe parenchymal damage in the brain. Although viral latency in neurons is very common in the population, it remains unclear why certain individuals develop HSE. Here we explore potential host genetic variants predisposing to HSE. In order to investigate this we used a rat HSE model comparing the HSE susceptible SHR (Spontaneously Hypertensive Rats) with the asymptomatic infection of BN (Brown Norway). Notably, both strains have HSV-1 spread to the CNS at four days after infection. A genome wide linkage analysis of 29 infected HXB/BXH RILs (recombinant inbred lines-generated from the prior two strains), displayed variable susceptibility to HSE enabling the definition of a significant QTL (quantitative trait locus) named Hse6 towards the end of chromosome 4 (160.89-174Mb) containing the Vwf (von Willebrand factor) gene. This was the only gene in the QTL with both cis-regulation in the brain and included several non-synonymous SNPs (single nucleotide polymorphism). Intriguingly, in human chromosome 12 several SNPs within the intronic region between exon 43 and 44 of the VWF gene were associated with human HSE pathogenesis. In particular, rs917859 is nominally associated with an odds ratio of 1.5 (95% CI 1.11-2.02; p-value = 0.008) after genotyping in 115 HSE cases and 428 controls. Although there are possibly several genetic and environmental factors involved in development of HSE, our study identifies variants of the VWF gene as candidates for susceptibility in experimental and human HSE.
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14.
  • Andersson, C., et al. (författare)
  • MATCH-SALSA - Multi-scale Atmospheric Transport and CHemistry model coupled to the SALSA aerosol microphysics model - Part 1: Model description and evaluation
  • 2015
  • Ingår i: Geoscientific Model Development. - : Copernicus GmbH. - 1991-959X .- 1991-9603. ; 8:2, s. 171-189
  • Tidskriftsartikel (refereegranskat)abstract
    • © Author(s) 2015. We have implemented the sectional aerosol dynamics model SALSA (Sectional Aerosol module for Large Scale Applications) in the European-scale chemistry-transport model MATCH (Multi-scale Atmospheric Transport and Chemistry). The new model is called MATCH-SALSA. It includes aerosol microphysics, with several formulations for nucleation, wet scavenging and condensation. The model reproduces observed higher particle number concentration (PNC) in central Europe and lower concentrations in remote regions. The modeled PNC size distribution peak occurs at the same or smaller particle size as the observed peak at four measurement sites spread across Europe. Total PNC is underestimated at northern and central European sites and accumulation-mode PNC is underestimated at all investigated sites. The low nucleation rate coefficient used in this study is an important reason for the underestimation. On the other hand, the model performs well for particle mass (including secondary inorganic aerosol components), while elemental and organic carbon concentrations are underestimated at many of the sites. Further development is needed, primarily for treatment of secondary organic aerosol, in terms of biogenic emissions and chemical transformation. Updating the biogenic secondary organic aerosol (SOA) scheme will likely have a large impact on modeled PM2.5 and also affect the model performance for PNC through impacts on nucleation and condensation.
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15.
  • Bergh, Johan, 1983- (författare)
  • Structural investigation of SOD1 aggregates in ALS : identification of prion strains using anti-peptide antibodies
  • 2018
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative syndrome characterized by progressive degeneration of motor neurons that result in muscle wasting. The symptoms advance gradually to paralysis and eventually death. Most patients suffer from sporadic ALS (sALS) but 10% report a familial predisposition. Mutations in the gene encoding super­oxide dismutase-1 (SOD1) were the first identified cause of ALS. The disease mecha­nism is debated but there is a consensus that mutations in this protein confer a cytotoxic gain of function. SOD1 aggregates in motor neurons are hallmarks of ALS both in patients and in transgenic mouse models expressing a mutated form of human SOD1 (hSOD1). Recently, our group showed that SOD1 aggregates are present also in sALS patients, thus indicating a broader involvement of this protein in ALS. Misfolding and aggregation of SOD1 are dif­ficult to study in vivo since aggregate concentration in the central nervous system (CNS) is exceedingly low. The aim of this thesis was to find a method circumventing this problem to investigate the hSOD1 aggregate structure, distribution and spread in ALS disease.Many studies provide circumstantial evidence that the wild-type hSOD1 protein can be neurotoxic. We developed the first homozygous mouse model that highly overexpresses the wild-type enzyme. These mice developed an ALS-like syndrome and become terminally ill after around 370 days. Motor neuron loss and SOD1 aggregate accumulation in the CNS were observed. This lends further support to the hypothesis of a more general involve­ment of SOD1 in human disease.A panel of polyclonal antibodies covering 90% of the SOD1 protein was developed by our laboratory. These antibodies were shown to be highly specific for misfolded SOD1. Aggre­gated hSOD1 was purified from the CNS of terminally ill hSOD1 mice. Disordered segments in aggregated hSOD1 could be identified with these antibodies. Two aggregate strains with different structural architectures, molecular properties, and growth kinetics, were found using this novel method. The strains, denoted A and B, were also associated with different disease progression. Aggregates formed in vitro were structurally different from these strains. The results gave rise to questions about aggregate development and possible prion-like spread. To investigate this, inoculations of purified strain A and B hSOD1 seeds was performed in lumbar spinal cords of 100-day old mice carrying a hSOD1G85R mutation. Mice seeded with A or B aggregates developed premature signs of ALS and became terminally ill 200 days earlier than mice inoculated with control preparation. Interestingly, a tem­plated spread of aggregates along the neuraxis was concomitantly observed, with strain A and B provoking the buildup of their respective hSOD1 aggregate structure. The phenotypes initiated by the A and B strains differed regarding progression rates, distribution, end-stage aggregate levels, and histopathology. To further establish the importance of hSOD1 aggregates in human disease, purification and inoculation of aggregate seeds from spinal cords of ALS patients and mice carrying the hSOD1G127X mutation were performed. Inoculation of both human and mouse seeds as described above, induced strain A aggregation and premature fatal ALS-like disease.In conclusion, the data presented in this thesis provide a new, straightforward method for characterization of aggregate strains in ALS, and plausibly also in other neurodegen­erative diseases. Two different prion strains of hSOD1 aggregates were identified in mice that resulted in ALS-like disease. Emerging data suggest that prion-like growth and spread of hSOD1 aggregation could be the primary pathogenic mechanism not only in hSOD1 transgenic models, but also in human ALS.
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17.
  • Bergström, Aileen L., et al. (författare)
  • An integrative review of information and communication technology based support interventions for carers of home dwelling older people
  • 2017
  • Ingår i: Technology and Disability. - : IOS Press. - 1055-4181 .- 1878-643X. ; 29:1-2, s. 1-14
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND A growing number of studies of informal carers of older people reveal positive results concerning support via Information and Communication Technologies (ICT). Systematic examination of factors that have a potential impact on carer outcomes are needed to inform future research.OBJECTIVE To explore studies concerning ICT support of adult carers of older people and to identify study characteristics that have a potential impact on carer outcomes.METHODS This integrative review includes 123 studies published since 2005. Fundamental questions for designing sensitive support interventions; ‘who, what, and how’ were applied to a synthesis of the results.RESULTS Identified characteristics from the studies responding to the who question included variables of the carers, such as their relationship with the care recipient or their ethnicity. Characteristics related to the what question related to the types of interventions, and the how question concerned the different services or programs offered, the idiosyncratic needs of the carers, and the types of technologies used.CONCLUSION Results are discussed according to micro, meso and macro levels of analysis. This extensive review can inform future studies and highlight the evidence in the area for decision makers, practitioners and/or NGOs working with innovative forms of support for carers of older people
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18.
  • Bergström, Aileen L., et al. (författare)
  • Complex negotiations : The lived experience of enacting agency after a stroke
  • 2015
  • Ingår i: Scandinavian Journal of Occupational Therapy. - : Informa UK Limited. - 1103-8128 .- 1651-2014. ; 22:1, s. 43-53
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: This qualitative, longitudinal, descriptive study aimed to understand the lived experience of enacting agency, and to describe the phenomenon of agency and the meaning structure of the phenomenon during the year after a stroke. Agency is defined as making things happen in everyday life through one's actions. Methods: This study followed six persons (three men and three women, ages 63 to 89), interviewed on four separate occasions. Interview data were analysed using the Empirical Phenomenological Psychological method. Results: The main findings showed that the participants experienced enacting agency in their everyday lives after stroke as negotiating different characteristics over a span of time, a range of difficulty, and in a number of activities, making these negotiations complex. The four characteristics described how the participants made things happen in their everyday lives through managing their disrupted bodies, taking into account their past and envisioning their futures, dealing with the world outside themselves, and negotiating through internal dialogues. Conclusions: This empirical evidence regarding negotiations challenges traditional definitions of agency and a new definition of agency is proposed. Understanding clients' complex negotiations and offering innovative solutions to train in real-life situations may help in the process of enabling occupations after a stroke.
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19.
  • Bergström, Aileen L., et al. (författare)
  • Participation in everyday life and life satisfaction in persons with stroke and their caregivers 3–6 months after onset
  • 2015
  • Ingår i: Journal of Rehabilitation Medicine. - : Medical Journals Sweden AB. - 1650-1977 .- 1651-2081. ; 47:6, s. 508-515
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To explore and describe persons with stroke and their caregivers' restrictions in participation in everyday occupations, i.e. occupational gaps, 3-6 months post-stroke, in relation to life satisfaction, combined life satisfaction, caregiver burden, perceived impact of stroke, and activities of daily living. Design: Cross-sectional study. Subjects: Persons with stroke and their caregivers (105 dyads). Methods: The Occupational Gaps Questionnaire, Life Satisfaction Checklist, Caregiver Burden Scale, Stroke Impact Scale and Barthel Index were used. Correlations were analysed with Spearman's rank, and regression analyses used life satisfaction as the dependent variable. Results: At least one person in 86% of the dyads perceived restrictions in participation, with the most common gap in travelling for pleasure. Correlations were low between the numbers of occupational gaps and life satisfaction (R=-0.33, R=-0.31); however, life satisfaction accounted for occupational gaps both for persons with stroke and for caregivers. A greater number of occupational gaps were perceived in the dyads with combined low levels of life satisfaction compared with those with combined high levels of life satisfaction. Conclusion: Participation in everyday occupations is related to life satisfaction even for caregivers of persons with stroke. The results of this study add to our knowledge about the stroke-caregiver dyad and will help to inform family-centred approaches within stroke rehabilitation.
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20.
  • Bergström, L. Magnus (författare)
  • Explaining the growth behavior of surfactant micelles
  • 2015
  • Ingår i: Journal of Colloid and Interface Science. - : Elsevier BV. - 0021-9797 .- 1095-7103. ; 440, s. 109-118
  • Tidskriftsartikel (refereegranskat)abstract
    • The growth behavior of surfactant micelles has been investigated from a theoretical point of view. It is demonstrated that predictions deduced from the spherocylindrical micelle model, which considers micelles that are only able to grow in the length direction, are inconsistent with experimental measurements. Accordingly, the rise in aggregation numbers above a certain concentration, roughly corresponding to the second critical micelle concentration, appears to be much stronger than predicted by the spherocylindrical micelle model. On the other hand, predictions deduced from the general micelle model, which considers micelles that are able to grow with respect to both width and length, show excellent agreement with experimental observations. The latter theory is based on bending elasticity and it is demonstrated that the associated three parameters spontaneous curvature, bending rigidity and saddle-splay constant may all be determined for a micellar system from experimental measurements of the aggregation number as a function of surfactant concentration. The three parameters turn out to influence the appearance of a micellar growth curve rather differently. In accordance, the location of the second cmc is mainly determined by the saddle-splay constant and the bending rigidity. The shape of the growth curve, when going from the region of weakly growing micelles at low surfactant concentrations to strongly growing micelles above the second cmc, is mainly influenced by the bending rigidity.
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21.
  • Bergström, L. Magnus (författare)
  • Second CMC in surfactant micellar systems
  • 2016
  • Ingår i: Current Opinion in Colloid & Interface Science. - : Elsevier BV. - 1359-0294 .- 1879-0399. ; 22, s. 46-50
  • Forskningsöversikt (refereegranskat)abstract
    • Experimental reports of surfactant systems displaying a second critical micelle concentration (second CMC) have been surveyed. It turns out that surfactant micelles usually show a growth behavior with some typical features. (i) Micelles grow weakly at low surfactant concentrations but may switch to a much stronger growth behavior at higher concentrations. The second CMC is defined as the point of transition from wealdy to strongly growing micelles. (ii) Micelles are found to be non-spherically shaped below the second CMC. (iii) At the second CMC micelles are found to be much smaller, with aggregation numbers typically 100-200, than expected for flexible micelles. (iv) Micelles of intermediate size are present in a narrow concentration regime close to the second CMC. (v) Micelles grow much stronger above the second CMC than expected from a sphere-to-rod transition. The conventional spherocylindrical micelle model predicts a smooth growth behavior that contradicts the appearance of a second CMC. Modifying the model by means of including swollen end caps neither account for the presence of micelles with intermediate size, nor the strong growth behavior above the second CMC. Taking into account micelle flexibility is not consistent with the rather low micelle aggregation numbers observed at the second CMC. On the other hand, a recently proposed alternative theoretical approach, the general micelle model, have been demonstrated to take into account basically all features that are typical of experimentally observed micellar growth behaviors.
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22.
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23.
  • Bergström, Marcus, et al. (författare)
  • Immunological Profiling of Haemodialysis Patients and Young Healthy Individuals with Implications for Clinical Regulatory T Cell Sorting
  • 2015
  • Ingår i: Scandinavian Journal of Immunology. - : Wiley. - 0300-9475 .- 1365-3083. ; 81:5, s. 318-324
  • Tidskriftsartikel (refereegranskat)abstract
    • With the increasing interest in clinical trials with regulatory T cells (Tregs), immunological profiling of prospective target groups and standardized procedures for Treg isolation are needed. In this study, flow cytometry was used to assess peripheral blood lymphocyte profiles of young healthy individuals and patients undergoing haemodialysis treatment. Tregs obtained from the former may be used in haematopoietic stem cell transplantation and Tregs from the latter in the prevention of kidney transplant rejection. FOXP3 mRNA expression with accompanying isoform distribution was also assessed by the quantitative reverse transcriptase polymerase chain reaction. Flow-cytometric gating strategies were systematically analysed to optimize the isolation of Tregs. Our findings showed an overall similar immunological profile of both cohorts in spite of great differences in both age and health. Analysis of flow-cytometric gating techniques highlighted the importance of gating for both CD25high and CD127low expression in the isolation of FOXP3-positive cells. This study provides additional insight into the immunological profile of young healthy individuals and uraemic patients as well as in-depth analysis of flow-cytometric gating strategies for Treg isolation, supporting the development of Treg therapy using cells from healthy donors and uraemic patients.
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24.
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25.
  • Bergström, Stig M., et al. (författare)
  • Local and trans-Atlantic chemostratigraphic significance of new δ13Ccarb data from the Sandbian and Katian Stages (Middle–Upper Ordovician) of the Oslo region, Norway
  • 2017
  • Ingår i: GFF. - : Informa UK Limited. - 1103-5897 .- 2000-0863. ; 139:4, s. 289-300
  • Tidskriftsartikel (refereegranskat)abstract
    • Late Sandbian to early Katian δ13Ccarb chemostratigraphy has in Norway been described in only two previous reports that dealt with two geographically rather widely separated areas, namely the Oslo-Asker district and the Nes-Hamar district. No data have been available from the Ordovician outcrop areas between these districts that could help clarify the partly unclear regional stratigraphic relations across the Oslo region. A chemostratigraphic study of the classical road section at Tønnerud in the northwestern Hadeland district about halfway between the previously investigated districts resulted in the recognition of two δ13C excursions, namely one in the uppermost Furuberget Formation tentatively identified as the Guttenberg Isotopic Carbon Excursion and one in the lower Solvang Formation that is classified as the KOPE (RAKVERE) excursion. Based on these results, the Furuberget and Solvang formations are interpreted to be separated by a significant gap in the study area corresponding to the Oandu and lower Rakvere regional Baltoscandic stages. This suggests that the Tønnerud succession is less complete stratigraphically than those in the Oslo-Asker district. Similar gaps are not uncommon in this interval in Baltoscandia and in North America and probably reflect both eustatic and local epeirogenetic movements that make it difficult to establish a regionally applicable sequence stratigraphy.
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26.
  • Crisci, E., et al. (författare)
  • Complement Opsonization Promotes Herpes Simplex Virus 2 Infection of Human Dendritic Cells
  • 2016
  • Ingår i: Journal of Virology. - : American Society for Microbiology. - 0022-538X .- 1098-5514. ; 90:10, s. 4939-4950
  • Tidskriftsartikel (refereegranskat)abstract
    • Herpes simplex virus 2 (HSV-2) is one of the most common sexually transmitted infections globally, with a very high prevalence in many countries. During HSV-2 infection, viral particles become coated with complement proteins and antibodies, both present in genital fluids, which could influence the activation of immune responses. In genital mucosa, the primary target cells for HSV-2 infection are epithelial cells, but resident immune cells, such as dendritic cells (DCs), are also infected. DCs are the activators of the ensuing immune responses directed against HSV-2, and the aim of this study was to examine the effects opsonization of HSV-2, either with complement alone or with complement and antibodies, had on the infection of immature DCs and their ability to mount inflammatory and antiviral responses. Complement opsonization of HSV-2 enhanced both the direct infection of immature DCs and their production of new infectious viral particles. The enhanced infection required activation of the complement cascade and functional complement receptor 3. Furthermore, HSV-2 infection of DCs required endocytosis of viral particles and their delivery into an acid endosomal compartment. The presence of complement in combination with HSV-1- or HSV-2-specific antibodies more or less abolished HSV-2 infection of DCs. Our results clearly demonstrate the importance of studying HSV-2 infection under conditions that ensue in vivo, i.e., conditions under which the virions are covered in complement fragments and complement fragments and antibodies, as these shape the infection and the subsequent immune response and need to be further elucidated. During HSV-2 infection, viral particles should become coated with complement proteins and antibodies, both present in genital fluids, which could influence the activation of the immune responses. The dendritic cells are activators of the immune responses directed against HSV-2, and the aim of this study was to examine the effects of complement alone or complement and antibodies on HSV-2 infection of dendritic cells and their ability to mount inflammatory and antiviral responses. Our results demonstrate that the presence of antibodies and complement in the genital environment can influence HSV-2 infection under in vitro conditions that reflect the in vivo situation. We believe that our findings are highly relevant for the understanding of HSV-2 pathogenesis.
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27.
  • Deininger, Anne, 1987- (författare)
  • Effects of inorganic nitrogen and organic carbon on pelagic food webs in boreal lakes
  • 2017
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Anthropogenic activities are increasing inorganic nitrogen (N) loadings to lakes in the northern hemisphere. In many boreal lakes phytoplankton are N limited, wherefore enhanced N input may affect the productivity of pelagic food webs. Simultaneously, global change causes increased inflows of terrestrial dissolved organic carbon (DOC) to boreal lakes. Between clear and humic lakes, whole lake primary and consumer production naturally differs. However, research is inconclusive as to what controls pelagic production in these lakes. Further, it is unclear how DOC affects the response of the pelagic food web to enhanced inorganic N availability. The overarching goal of this thesis was to study the effects of inorganic N and organic C for pelagic food webs in boreal lakes. In the thesis, I first identified the main drivers of pelagic production during summer in eight non-manipulated Swedish boreal lakes with naturally low or high DOC. Then I investigated how increased N availability affects the pelagic food chain, and how the response differs with DOC. Therefore, whole lake inorganic N fertilization experiments were conducted in six Swedish boreal lakes across a DOC gradient (low, medium, high) divided into three lake pairs (control, N enriched) with one reference and two impact years. In each lake, I also investigated the response of zooplankton growth using in situ mesocosm experiments excluding planktivores. I found that humic boreal lakes had lower phytoplankton production and biomass than clear water lakes. Further, phytoplankton community composition and food quality differed with DOC. However, high DOC did not reduce pelagic energy mobilization or zooplankton biomass, but promoted a higher dominance of cladoceran relative to copepod species. N addition clearly enhanced phytoplankton biomass and production in the experimental lakes. However, this stimulating N effect decreased with DOC as caused by light limitation. Further, the newly available phytoplankton energy derived from N addition was not efficiently transferred to zooplankton, which indicates a mismatch between producer energy supply and consumer energy use. Indeed, the mesocosm experiment revealed that decreased food quality of phytoplankton in response to N addition resulted in reduced food web performance, especially in clearer lakes. In humic lakes, zooplankton production and food web efficiency were clearly more resilient to N addition. In summary, my thesis suggests that any change in the landscape that enhances inorganic N availability will especially affect pelagic food webs in clear water lakes. In contrast, brownification will result in more lakes being resilient to eutrophication caused by enhanced N deposition.
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28.
  • Deininger, Anne, et al. (författare)
  • Pelagic food web response to whole lake N fertilization
  • 2017
  • Ingår i: Limnology and Oceanography. - : Wiley. - 0024-3590 .- 1939-5590. ; 62:4, s. 1498-1511
  • Tidskriftsartikel (refereegranskat)abstract
    • Anthropogenic activities are increasing inorganic nitrogen (N) loadings to unproductive boreal lakes. In many of these lakes phytoplankton are N limited, consequently N fertilization may affect ecosystem productivity and consumer resource use. Here, we conducted whole lake inorganic N fertilization experiments with six small N limited unproductive boreal lakes (three control and three N enriched) in an area receiving low N deposition with one reference and two impact years. Our aim was to assess the effects of N fertilization on pelagic biomass production and consumer resource use. We found that phytoplankton primary production (PP) and biomass, and the PP: bacterioplankton production ratio increased after fertilization. As expected, the relative contribution of phytoplankton derived resources (autochthony) that supported the crustacean zooplankton community increased. Yet, the response in the consumer community was modest with autochthony only increasing in one of the three major zooplankton groups and with no effect on zooplankton biomass. In conclusion, our findings imply that newly available phytoplankton energy derived from N fertilization was not efficiently transferred up to zooplankton, indicating a mismatch between producer energy supply and consumer energy use with potential accumulation of phytoplankton biomass as the result.
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29.
  • Deininger, Anne, et al. (författare)
  • Phytoplankton response to whole lake inorganic N fertilization along a gradient in dissolved organic carbon
  • 2017
  • Ingår i: Ecology. - : Wiley. - 0012-9658 .- 1939-9170. ; 98:4, s. 982-994
  • Tidskriftsartikel (refereegranskat)abstract
    • Global change has increased inorganic nitrogen (N) and dissolved organic carbon (DOC; i.e. ‘browning’) inputs to northern hemisphere boreal lakes. However, we do not know how phytoplankton in nutrient poor lake ecosystems of different DOC concentration respond to increased N availability. Here, we monitored changes in phytoplankton production, biomass and community composition in response to whole lake inorganic N fertilization in six boreal unproductive Swedish lakes divided into three lake pairs (control, N enriched) at three DOC levels (low, medium, high), with one reference year (2011) and two impact years (2012, 2013). We found that phytoplankton biomass and production decreased with DOC concentration before N fertilization. Further, phytoplankton community composition also differed with respect to DOC, with a dominance of non-flagellated autotrophs at low DOC towards an increasing dominance of flagellated autotrophs with increased lake DOC concentration. The N fertilization increased phytoplankton biomass and production in all lakes, but did not affect phytoplankton community composition. However, the net response in biomass and production to N fertilization declined with increasing DOC, implying that the lake DOC concentration is critical in order to infer phytoplankton responses to N fertilization, and that the system switches from being primarily nutrient limited to becoming increasingly light limited with increased DOC concentration. In conclusion, our results show that browning will reduce phytoplankton production and biomass and influence phytoplankton community composition, whereas increased inorganic N loadings from deposition, forestry or other land use will primarily enhance phytoplankton biomass and production. Together, any change in the landscape that enhances inorganic N availability will increase phytoplankton production and biomass, but the positive effects of N will be much weaker or even neutralized in browner lakes as caused by light limitation.
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30.
  • Eriksson, Leif, 1971-, et al. (författare)
  • Secular trend, seasonality and effects of a community-based intervention on neonatal mortality : follow-up of a cluster-randomised trial in Quang Ninh province, Vietnam
  • 2018
  • Ingår i: Journal of Epidemiology and Community Health. - : BMJ. - 0143-005X .- 1470-2738. ; 72:9, s. 776-782
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Little is know about whether the effects of community engagement interventions for child survival in low-income and middle-income settings are sustained. Seasonal variation and secular trend may blur the data. Neonatal mortality was reduced in a cluster-randomised trial in Vietnam where laywomen facilitated groups composed of local stakeholders employing a problem-solving approach for 3 years. In this analysis, we aim at disentangling the secular trend, the seasonal variation and the effect of the intervention on neonatal mortality during and after the trial.Methods: In Quang Ninh province, 44 communes were allocated to intervention and 46 to control. Births and neonatal deaths were assessed in a baseline survey in 2005, monitored during the trial in 2008–2011 and followed up by a survey in 2014. Time series analyses were performed on monthly neonatal mortality data.Results: There were 30 187 live births and 480 neonatal deaths. The intervention reduced the neonatal mortality from 19.1 to 11.6 per 1000 live births. The reduction was sustained 3 years after the trial. The control areas reached a similar level at the time of follow-up. Time series decomposition analysis revealed a downward trend in the intervention areas during the trial that was not found in the control areas. Neonatal mortality peaked in the hot and wet summers.Conclusions: A community engagement intervention resulted in a lower neonatal mortality rate that was sustained but not further reduced after the end of the trial. When decomposing time series of neonatal mortality, a clear downward trend was demonstrated in intervention but not in control areas.Trial registration number: ISRCTN44599712, Post-results.
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31.
  • Estrader, Marta, et al. (författare)
  • Origin of the large dispersion of magnetic properties in nanostructured oxides : FexO/Fe3O4 nanoparticles as a case study
  • 2015
  • Ingår i: Nanoscale. - : Royal Society of Chemistry (RSC). - 2040-3364 .- 2040-3372. ; 7:7, s. 3002-3015
  • Tidskriftsartikel (refereegranskat)abstract
    • The intimate relationship between stoichiometry and physicochemical properties in transition-metal oxides makes them appealing as tunable materials. These features become exacerbated when dealing with nanostructures. However, due to the complexity of nanoscale materials, establishing a distinct relationship between structure-morphology and functionalities is often complicated. In this regard, in the FexO/Fe3O4 system a largely unexplained broad dispersion of magnetic properties has been observed. Here we show, thanks to a comprehensive multi-technique approach, a clear correlation between the magneto-structural properties in large (45 nm) and small (9 nm) FexO/Fe3O4 core/shell nanoparticles that can explain the spread of magnetic behaviors. The results reveal that while the FexO core in the large nanoparticles is antiferromagnetic and has bulk-like stoichiometry and unit-cell parameters, the FexO core in the small particles is highly non-stoichiometric and strained, displaying no significant antiferromagnetism. These results highlight the importance of ample characterization to fully understand the properties of nanostructured metal oxides.
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32.
  • Faithfull, Carolyn L., et al. (författare)
  • Food web efficiency differs between humic and clear water lake communities in response to nutrients and light
  • 2015
  • Ingår i: Oecologia. - : Springer Science and Business Media LLC. - 0029-8549 .- 1432-1939. ; 177:3, s. 823-835
  • Tidskriftsartikel (refereegranskat)abstract
    • This study demonstrates that clear and humic freshwater pelagic communities respond differently to the same environmental stressors, i.e. nutrient and light availability. Thus, effects on humic communities cannot be generalized from existing knowledge about these environmental stressors on clear water communities. Small humic lakes are the most numerous type of lake in the boreal zone, but little is known about how these lakes will respond to increased inflows of nutrients and terrestrial dissolved organic C (t-DOC) due to climate change and increased human impacts. Therefore, we compared the effects of nutrient addition and light availability on pelagic humic and clear water lake communities in a mesocosm experiment. When nutrients were added, phytoplankton production (PPr) increased in both communities, but pelagic energy mobilization (PEM) and bacterial production (BP) only increased in the humic community. At low light conditions, the addition of nutrients led to increased PPr only in the humic community, suggesting that, in contrast to the clear water community, humic phytoplankton were already adapted to lower ambient light levels. Low light significantly reduced PPr and PEM in the clear water community, but without reducing total zooplankton production, which resulted in a doubling of food web efficiency (FWE = total zooplankton production/PEM). However, total zooplankton production was not correlated with PEM, PPr, BP, PPr:BP or C:nutrient stoichiometry for either community type. Therefore, other factors such as food chain length, food quality, ultra-violet radiation or duration of the experiment, must have determined total zooplankton production and ultimately FWE.
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33.
  • Franzen-Rohl, E., et al. (författare)
  • Herpes simplex virus specific T cell response in a cohort with primary genital infection correlates inversely with frequency of subsequent recurrences
  • 2017
  • Ingår i: Sexually Transmitted Infections. - : BMJ. - 1368-4973 .- 1472-3263. ; 93:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives During the last decades, a changing epidemiological pattern of genital herpes simplex virus (HSV) infection has emerged. Primary infection is now caused as often by HSV-1 as by HSV-2. Once established, HSV can be reactivated leading to recurrent mucocutaneous lesions as well as meningitis. Why some otherwise immune-competent individuals experience severe and frequent recurrences is not known, and the immunological mechanism underlying recurrent symptomatic HSV infection is not fully understood. In this study, we investigate and characterise the immune response of patients with first episode of HSV genital infection and its relation to the frequency of symptomatic recurrences. Methods In this cohort study, clinical and immunological data were collected from 29 patients who were followed 1 year after presenting with a first episode of genital or meningeal HSV infection. They were classified by PCR and serology as those with primary HSV-1, primary HSV-2 and non-primary HSV-2 infection. Results HSV-specific interleukin(Il)-4 and II-10 responses at first visit were higher in primary infected HSV-2 infected patients experiencing lower numbers of recurrences during subsequent year. Conclusions The median number of recurrences following primary HSV-2 genital infection may partly be predicted by the strength of an early HSV-specific IL-4 and IL-10 response.
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34.
  • Henmyr, Viktor, et al. (författare)
  • Characterization of genetic variation in TLR8 in relation to allergic rhinitis
  • 2015
  • Ingår i: Allergy. European Journal of Allergy and Clinical Immunology. - : Wiley-Blackwell. - 0105-4538 .- 1398-9995.
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: A previous investigation of all 10 TLR-genes for associations with allergic rhinitis (AR) detected a number of significant SNPs in the TLR8 locus. The associations indicated that an accumulation of rare variants could explain the signal. The present study therefore searches for rare variants in the TLR8 region and also investigates the reproducibility of previous SNP associations.METHODS: The TLR8 gene was re-sequenced in 288 AR patients from Malmö and the data was compared with publically available data. Seven previously AR-associated SNPs from TLR8 were analyzed for AR-associations in 422 AR patients and 859 controls from the BAMSE cohort. The associations detected in present and previous studies were compared.RESULTS: Sequencing detected 13 polymorphisms (3 promotor, 10 coding) among 288 AR patients. Four of the coding polymorphisms were rare (MAF <1%) and three of those were novel. Two coding polymorphisms were benign missense mutations and the rest were synonymous. Comparison with 1000Genomes and Exome Aggregation Consortium data revealed no accumulation of rare variants in the AR cases. The AR-association tests made using the BAMSE cohort yielded 5 P-values < 0.05. Tests of IgE-levels yielded 4 significant SNP associations to birch pollen. Comparing results between different populations revealed opposing risk alleles, different gender effects and response to different allergens in the different populations.CONCLUSIONS: Rare variants in TLR8 are not associated with AR. Comparison of present and previous association studies reveal contradictory results for common variants. Thus, no associations exist between genetic variation in TLR8 and AR. This article is protected by copyright. All rights reserved.
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35.
  • Henmyr, Viktor, et al. (författare)
  • Characterization of genetic variation in TLR8 in relation to allergic rhinitis
  • 2015
  • Ingår i: Allergy. European Journal of Allergy and Clinical Immunology. - : Wiley. - 0105-4538 .- 1398-9995.
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: A previous investigation of all 10 TLR-genes for associations with allergic rhinitis (AR) detected a number of significant SNPs in the TLR8 locus. The associations indicated that an accumulation of rare variants could explain the signal. The present study therefore searches for rare variants in the TLR8 region and also investigates the reproducibility of previous SNP associations. METHODS: The TLR8 gene was re-sequenced in 288 AR patients from Malmö and the data was compared with publically available data. Seven previously AR-associated SNPs from TLR8 were analyzed for AR-associations in 422 AR patients and 859 controls from the BAMSE cohort. The associations detected in present and previous studies were compared. RESULTS: Sequencing detected 13 polymorphisms (3 promotor, 10 coding) among 288 AR patients. Four of the coding polymorphisms were rare (MAF <1%) and three of those were novel. Two coding polymorphisms were benign missense mutations and the rest were synonymous. Comparison with 1000Genomes and Exome Aggregation Consortium data revealed no accumulation of rare variants in the AR cases. The AR-association tests made using the BAMSE cohort yielded 5 P-values < 0.05. Tests of IgE-levels yielded 4 significant SNP associations to birch pollen. Comparing results between different populations revealed opposing risk alleles, different gender effects and response to different allergens in the different populations. CONCLUSIONS: Rare variants in TLR8 are not associated with AR. Comparison of present and previous association studies reveal contradictory results for common variants. Thus, no associations exist between genetic variation in TLR8 and AR. This article is protected by copyright. All rights reserved.
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36.
  • Jenkin, M. E., et al. (författare)
  • The CRI v2.2 reduced degradation scheme for isoprene
  • 2019
  • Ingår i: Atmospheric Environment. - : Elsevier BV. - 1873-2844 .- 1352-2310. ; 212:1 Sept., s. 172-182
  • Tidskriftsartikel (refereegranskat)abstract
    • The reduced representation of isoprene degradation in the Common Representative Intermediates (CRI)mechanism has been systematically updated, using the Master Chemical Mechanism (MCM v3.3.1)as a reference benchmark, with the updated mechanism being released as CRI v2.2. The complete isoprene degradation mechanism in CRI v2.2 consists of 186 reactions of 56 closed shell and free radical species, this being an order of magnitude reduction in size compared with MCM v3.3.1. The chemistry initiated by reaction with OH radicals, NO3 radicals and ozone (O3)is treated. An overview of the updates is provided, within the context of reported kinetic and mechanistic information. The revisions mainly relate to the OH-initiated chemistry, which tends to dominate under atmospheric conditions, although these include updates to the chemistry of products that are also generated from the O3- and NO3-initiated oxidation. The revisions have impacts in a number of key areas, including recycling of HOx and NOx. The performance of the CRI v2.2 isoprene mechanism has been compared with those of the preceding version (CRI v2.1)and the reference MCM v3.3.1 over a range of relevant conditions, using a box model of the tropical forested boundary layer. In addition, tests are carried out to ensure that the performance of MCM v3.3.1 remains robust to more recently reported information. CRI v2.2 has also been implemented into the STOCHEM chemistry-transport model, with a customized close-variant of CRI v2.2 implemented into the EMEP MSC-W chemistry-transport model. The results of these studies are presented and used to illustrate the global-scale impacts of the mechanistic updates on HOx radical concentrations.
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37.
  • Johansson, Leif B. G., et al. (författare)
  • An azide functionalized oligothiophene ligand - A versatile tool for multimodal detection of disease associated protein aggregates
  • 2015
  • Ingår i: Biosensors & bioelectronics. - : Elsevier. - 0956-5663 .- 1873-4235. ; 63, s. 204-211
  • Tidskriftsartikel (refereegranskat)abstract
    • Ligands for identifying protein aggregates are of great interest as such deposits are the pathological hallmark of a wide range of severe diseases including Alzheimers and Parkinsons disease. Here we report the synthesis of an azide functionalized fluorescent pentameric oligothiophene that can be utilized as a ligand for multimodal detection of disease-associated protein aggregates. The azide functionalization allows for attachment of the ligand to a surface by conventional click chemistry without disturbing selective interaction with protein aggregates and the oligothiophene-aggregate interaction can be detected by fluorescence or surface plasmon resonance. In addition, a methodology where the oligothiophene ligand is employed as a capturing molecule selective for aggregated proteins in combination with an antibody detecting a distinct peptide/protein is also presented. We foresee that this methodology will offer the possibility to create a variety of multiplex sensing systems for sensitive and selective detection of protein aggregates, the pathological hallmarks of several neurodegenerative diseases.
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38.
  • Jonsson, Marina, et al. (författare)
  • Experiences of Daily Life Among Adolescents With Asthma - A Struggle With Ambivalence
  • 2017
  • Ingår i: Journal of Pediatric Nursing. - : Elsevier BV. - 0882-5963 .- 1532-8449. ; 35, s. 23-29
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: There is limited knowledge about how adolescents with asthma view their disease in daily life and how these views impact on management. The aim of this study was to describe experiences of daily life, with particular focus on thoughts, feelings and management of adolescents with asthma.METHODS: In this qualitative study, data were obtained from 10 interviews with adolescents (aged 16-18 years) with asthma recruited from the Swedish population-based prospective birth cohort, BAMSE. Data were analysed through Systematic Text Condensation.RESULTS: Experiences of daily life among adolescents with asthma were defined in four categories: Insight and understanding; Asthma not the focus of daily life; Being acknowledged and, Being affected by asthma symptoms. The adolescents had developed an insight into and understanding of their disease, but did not want asthma to be the focus of their daily lives. The adolescents wanted their asthma to be acknowledged, but not to the point that they were defined by their asthma. They reported having many asthma symptoms, especially during physical activity, but also described a desire to feel healthy, "normal" and like their peers.CONCLUSIONS: Having asthma in adolescence involves several struggles with ambivalence between adapting socially, feeling healthy and managing one's asthma.IMPLICATIONS IN CLINICAL PRACTICE: The provision of person-centred care may be one way to handle the ambivalence among adolescents with asthma and thereby help them to manage their asthma.
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39.
  • Le May, Marie, et al. (författare)
  • Activation of the rat hypothalamic supramammillary nucleus by food anticipation, food restriction or ghrelin administration
  • 2019
  • Ingår i: Journal of Neuroendocrinology. - : Wiley. - 0953-8194 .- 1365-2826. ; 31:7
  • Tidskriftsartikel (refereegranskat)abstract
    • The circulating orexigenic hormone ghrelin targets many brain areas involved in feeding control and signals via a dedicated receptor, the growth hormone secretagogue receptor 1A. One unexplored target area for ghrelin is the supramammillary nucleus (SuM), a hypothalamic area involved in motivation and reinforcement and also recently linked to metabolic control. Given that ghrelin binds to the SuM, we explored whether SuM cells respond to ghrelin and/or are activated when endogenous ghrelin levels are elevated. We found that peripheral ghrelin injection activates SuM cells in rats, reflected by an increase in the number of cells expressing c-Fos protein in this area, as welll as by the predominantly excitatory response of single SuM cells recorded in in vivo electrophysiological studies. Further c-Fos mapping studies reveal that this area is also activated in rats in situations when circulating ghrelin levels are known to be elevated: in food-restricted rats anticipating the consumption of food and in fed rats anticipating the consumption of an energy-dense food. We also show that intra-SuM injection of ghrelin induces a feeding response in rats suggesting that, if peripheral ghrelin is able to access the SuM, it may have direct effects on this brain region. Collectively, our data demonstrate that the SuM is activated when peripheral ghrelin levels are high, further supporting the emerging role for this brain area in metabolic and feeding control. © 2018 The Authors. Journal of Neuroendocrinology published by John Wiley & Sons Ltd on behalf of British Society for Neuroendocrinology
  •  
40.
  • Lindfors, Petra, et al. (författare)
  • Stress in paid and unpaid work as related to salivary cortisol measures and subjective health complaints in women working in the public sector
  • 2017
  • Konferensbidrag (refereegranskat)abstract
    • Purpose: From a biopsychosocial approach, moderate intensity and variation between demands of different life domains are central to health. Focusing on different aspects of work and non-work demands, we investigated how total workload (TWL) and work-family conflict (WFC) related to the stress marker cortisol and to subjective health complaints (SHC) among women working in the public sector. Overall, we hypothesized that more TWL and WFC would be reflected in poorer health.Design/methodology: Data came from a study of 250 women working within the health care sector. All provided self-reports in questionnaires on time spent on TWL and associated stress perceptions, WFC and SHC. A subsample of 68 women provided salivary samples during one workday. These samples were analyzed for cortisol and used to compute aggregate cortisol measures. Hierarchical regression analyses were performed to investigate how TWL and WFC were related to cortisol and SHC respectively.Results: TWL stress from unpaid work was associated with cortisol. Also, stress from both paid and unpaid work, and TWL-stress, were related to SHC. Importantly, number of hours spent on paid and unpaid work were not linked to any health-related measure. Instead, stress perceptions were associated with both cortisol and SHC. This underscores the importance of individuals’ experiences of demands from different life domains for different health-related measures.Limitations: We included only women.Research/practical implications: Time use data are insufficient meaning that self-reports of individual experiences are needed.Originality/value: Combining biomarker data with self-reports is an obvious strength.
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41.
  • Matic, L. P., et al. (författare)
  • Novel Multiomics Profiling of Human Carotid Atherosclerotic Plaques and Plasma Reveals Biliverdin Reductase B as a Marker of Intraplaque Hemorrhage
  • 2018
  • Ingår i: JACC: Basic to Translational Science. - : Elsevier BV. - 2452-302X. ; 3:4, s. 464-480
  • Tidskriftsartikel (refereegranskat)abstract
    • Clinical tools to identify individuals with unstable atherosclerotic lesions are required to improve prevention of myocardial infarction and ischemic stroke. Here, a systems-based analysis of atherosclerotic plaques and plasma from patients undergoing carotid endarterectomy for stroke prevention was used to identify molecular signatures with a causal relationship to disease. Local plasma collected in the lesion proximity following clamping prior to arteriotomy was profiled together with matched peripheral plasma. This translational workflow identified biliverdin reductase B as a novel marker of intraplaque hemorrhage and unstable carotid atherosclerosis, which should be investigated as a potential predictive biomarker for cardiovascular events in larger cohorts.
  •  
42.
  • Michalke, B., et al. (författare)
  • An approach for manganese biomonitoring using a manganese carrier switch in serum from transferrin to citrate at slightly elevated manganese concentration
  • 2015
  • Ingår i: Journal of Trace Elements in Medicine and Biology. - : Elsevier BV. - 0946-672X .- 1878-3252. ; 32, s. 145-154
  • Tidskriftsartikel (refereegranskat)abstract
    • After high-dose-short-term exposure (usually from occupational exposure) and even more under low-dose long term exposure (mainly environmental) manganese (Mn) biomonitoring is still problematic since these exposure scenarios are not necessarily reflected by a significant increase of total Mn in blood or serum. Usually, Mn concentrations of exposed and unexposed persons overlap and individual differentiation is often not possible. In this paper Mn speciation on a large sample size (n=180) was used in order to be able to differentiate between highly Mn-exposed or low or unexposed individuals at low total Mn concentration in serum (Mn(S)). The whole sample set consisted of three subsets from Munich, Emilia Romagna region in Italy and from Sweden. It turned out that also at low total Mn(S) concentrations a change in major Mn carriers in serum takes place from Mn-transferrin (Mn-Tf(S)) towards Mn-citrate (Mn-Cit(S)) with high statistical significance (p < 0.000002). This carrier switch from Mn-Tf(S) to Mn-Cit(S) was observed between Mn(S) concentrations of 1.5 mu g/L to ca. 1.7 mu g/L. Parallel to this carrier change, for sample donors from Munich where serum and cerebrospinal fluid were available, the concentration of Mn beyond neural barriers analysed as Mn in cerebrospinal fluid (Mn(C)) positively correlates to Mn-Cit(S) when Mn(S) concentration was above 1.7 mu g/L. The correlation between Mn-Cit(S) and Mn(C) reflects the facilitated Mn transport through neural barrier by means of Mn-citrate. Regional differences in switch points from Mn-Tf(S) to Mn-Cit(S) were observed for the three sample subsets. It is currently unknown whether these differences are due to differences in location, occupation, health status or other aspects. Based on our results, Mn-Cit(S) determination was considered as a potential means for estimating the Mn load in brain and CSF, i.e., it could be used as a biomarker for Mn beyond neural barrier. For a simpler Mn-Cit(S) determination than size exclusion chromatography inductively coupled plasma mass spectrometry (SEC-ICP-MS), ultrafiltration (UF) of serum samples was tested for suitability, the latter possibly being a preferred choice for routine occupational medicine laboratories. Our results revealed that UF could be an alternative if methodical prerequisites and limitations are carefully considered. These prerequisites were determined to be a thorough cleaning procedure at a minimum Mn(S) concentration >1.5 mu g/L, as at lower concentrations a wide scattering of the measured concentrations in comparison to the standardized SEC-ICP-MS results were observed.
  •  
43.
  • Mäkeläinen, Suvi, et al. (författare)
  • An ABCA4 loss-of-function mutation causes a canine form of Stargardt disease
  • 2019
  • Ingår i: PLOS Genetics. - : Public Library of Science. - 1553-7390 .- 1553-7404. ; 15:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Autosomal recessive retinal degenerative diseases cause visual impairment and blindness in both humans and dogs. Currently, no standard treatment is available, but pioneering gene therapy-based canine models have been instrumental for clinical trials in humans. To study a novel form of retinal degeneration in Labrador retriever dogs with clinical signs indicating cone and rod degeneration, we used whole-genome sequencing of an affected sib-pair and their unaffected parents. A frameshift insertion in the ATP binding cassette subfamily A member 4 (ABCA4) gene (c.4176insC), leading to a premature stop codon in exon 28 (p.F1393Lfs*1395), was identified. In contrast to unaffected dogs, no full-length ABCA4 protein was detected in the retina of an affected dog. The ABCA4 gene encodes a membrane transporter protein localized in the outer segments of rod and cone photoreceptors. In humans, the ABCA4 gene is associated with Stargardt disease (STGD), an autosomal recessive retinal degeneration leading to central visual impairment. A hallmark of STGD is the accumulation of lipofuscin deposits in the retinal pigment epithelium (RPE). The discovery of a canine homozygous ABCA4 loss-of-function mutation may advance the development of dog as a large animal model for human STGD.
  •  
44.
  • Noda, Jun, 1969, et al. (författare)
  • Aerosol from Biomass Combustion in Northern Europe: Influence of Meteorological Conditions and Air Mass History
  • 2019
  • Ingår i: Atmosphere. - 2073-4433. ; 10:12
  • Tidskriftsartikel (refereegranskat)abstract
    • Alkali-containing submicron particles were measured continuously during three months, including late winter and spring seasons in Gothenburg, Sweden. The overall aims were to characterize the ambient concentrations of combustion-related aerosol particles and to address the importance of local emissions and long-range transport for atmospheric concentrations in the urban background environment. K and Na concentrations in the particulate matter PM1 size range were measured by an Alkali aerosol mass spectrometer (Alkali-AMS) and a cluster analysis was conducted. Local meteorological conditions and trace gas and PM concentrations were also obtained for a nearby location. In addition, back trajectory analyses and chemical transport model (CTM) simulations were included for the evaluation. The Alkali-AMS cluster analysis indicated three major clusters: (1) biomass burning origin, (2) mixture of other combustion sources, and (3) marine origin. Low temperatures and low wind speed conditions correlated with high concentrations of K-containing particles, mainly owing to local and regional emissions from residential biomass combustion; transport of air masses from continental Europe also contribute to Cluster 1. The CTM results indicate that open biomass burning in the eastern parts of Europe may have contributed substantially to high PM2.5 concentrations (and to Cluster 1) during an episode in late March. According to the CTM results, the mixed cluster (2) is likely to include particles emitted from different source types and no single geographical source region seems to dominate for this cluster. The back trajectory analysis and meteorological conditions indicated that the marine origin cluster was correlated with westerly winds and high wind speed; this cluster had high concentrations of Na-containing particles, as expected for sea salt particles.
  •  
45.
  • Persson, K. I., et al. (författare)
  • Motivators and barriers for HIV testing among men who have sex with men in Sweden
  • 2016
  • Ingår i: Journal of Clinical Nursing. - : Wiley. - 0962-1067 .- 1365-2702. ; 25:23-24, s. 3605-3618
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims and objectives: To explore motivators and barriers to HIV testing and to assess the factors associated with testing among men who have sex with men. Background: Previous research has considered fear, worries and structural barriers as hindrances to HIV testing among men who have sex with men. However, few studies have included assessments of actual HIV testing when exploring barriers or motivators for such testing. Design: The design of the study was a stratified cross-sectional online survey (n=2373). Method: Factor analysis was conducted to analyse the barriers and motivators for HIV testing. Logistic regression analysis was conducted to assess predictors for HIV testing. Results: Many men who have sex with men test for HIV regularly, and specific reasons for testing were having unprotected sex or starting/ending a relationship. A lack of awareness and a perception of being at low risk for exposure were common reasons for never being tested. Fear and anxiety as well as barriers related to the use of test services remain important hindrances for testing. Predictors associated with having been tested within the past 12months were: younger age (15–25years old compared with 47+); knowledge on where to take an HIV test on short notice as well as having talked with a counsellor, having received condoms for free, or having had unprotected anal intercourse with casual partners within the last 12months. Conclusion: Easily accessible test services offering testing and counselling on short notice should be available for all men who have sex with men. Outreach activities, distribution of free condoms and testing at venues where men who have sex with men meet are important prevention add-ons that can contribute to increased awareness about HIV and testing. Relevance to clinical practice: Test services must ensure confidentiality and health care professionals who meet men who have sex with men for testing need competency with regards to men who have sex with men sexual health needs. © 2016 John Wiley & Sons Ltd
  •  
46.
  • Protudjer, Jennifer L. P., et al. (författare)
  • Milk-Related Symptoms and Immunoglobulin E Reactivity in Swedish Children from Early Life to Adolescence
  • 2018
  • Ingår i: Nutrients. - : MDPI. - 2072-6643. ; 10:5
  • Tidskriftsartikel (refereegranskat)abstract
    • Cow's milk often causes symptoms in infants. Whereas, some continue to experience symptoms through childhood, others become tolerant. Yet, the ages at which persistence and tolerance occur are less clear. Thus, we examined the age of onset and persistence of milk-related symptoms from early life to adolescence, and Immunoglobulin E (IgE) milk reactivity, focusing on gender differences in a large, population-based birth cohort. Overall, 20.0% (537/2985) of children, with a comparable gender distribution, had early life milk-related symptoms. At 16y, approximately 2% (62/2985) children had persistent symptoms and high milk IgE levels (e.g., median at 4 years: 1.5 kU(A)/L) that were beginning in early life. In contrast, 94% had transient symptoms and low median IgE levels (early life: 0.63 kU(A)/L, 8y: 0.72 kU(A)/L; 16 years: 1.1 kU(A)/L). Also, at 16 years, approximately 6% of females and 3% of males without any previously reported symptoms reported adolescent-onset of symptoms (p < 0.001). Such symptoms were almost exclusively gastrointestinal symptoms and were not associated with detectable IgE. In conclusion, early life milk-related symptoms are common, although most cases are transient by 16 years. Twice as many females vs. males report adolescent-onset symptoms, and particularly gastrointestinal symptoms. Children with persistent symptoms have both a higher prevalence and higher milk IgE levels, as compared to other phenotypes.
  •  
47.
  • Shafer, Aaron B A, et al. (författare)
  • Reply to Garner et al
  • 2016
  • Ingår i: Trends in Ecology & Evolution. - : Elsevier BV. - 0169-5347 .- 1872-8383. ; 31:2, s. 83-84
  • Tidskriftsartikel (refereegranskat)
  •  
48.
  • Skoglund, Sara, et al. (författare)
  • A novel explanation for the enhanced colloidal stability of silver nanoparticles in the presence of an oppositely charged surfactant
  • 2017
  • Ingår i: Physical Chemistry, Chemical Physics - PCCP. - : Royal Society of Chemistry (RSC). - 1463-9076 .- 1463-9084. ; 19:41, s. 28037-28043
  • Tidskriftsartikel (refereegranskat)abstract
    • The structural behavior in aqueous mixtures of negatively charged silver nanoparticles (Ag NPs) together with the cationic surfactants cetyltrimethylammonium bromide (CTAB) and dodecyltrimethylammonium chloride (DTAC), respectively, has been investigated using SANS and SAXS. From our SANS data analysis we are able to conclude that the surfactants self-assemble into micellar clusters surrounding the Ag NPs. We are able to quantify our results by means of fitting experimental SANS data with a model based on cluster formation of micelles with very good agreement. Based on our experimental results, we propose a novel mechanism for the stabilization of negatively charged Ag NPs in a solution of positively charged surfactants in which cluster formation of micelles in the vicinity of the particles prevents the particles from aggregating. Complementary SAXS and DLS measurements further support this novel way of explaining stabilization of small hydrophilic nanoparticles in surfactant-containing solutions.
  •  
49.
  •  
50.
  • Steingrimsson, S, et al. (författare)
  • Triclosan-coated sutures and sternal wound infections: a prospective randomized clinical trial.
  • 2015
  • Ingår i: European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology. - : Springer Science and Business Media LLC. - 1435-4373 .- 0934-9723. ; 34:12, s. 2331-2338
  • Tidskriftsartikel (refereegranskat)abstract
    • Surgical site infection is a common complication following cardiac surgery. Triclosan-coated sutures have been shown to reduce the rate of infections in various surgical wounds, including wounds after vein harvesting in coronary artery bypass grafting patients. Our purpose was to compare the rate of infections in sternotomy wounds closed with triclosan-coated or conventional sutures. A total of 357 patients that underwent coronary artery bypass grafting were included in a prospective randomized double-blind single-center study. The patients were randomized to closure of the sternal wound with either triclosan-coated sutures (Vicryl Plus and Monocryl Plus, Ethicon, Inc., Somerville, NJ, USA) (n=179) or identical sutures without triclosan (n=178). Patients were followed up after 30days (clinical visit) and 60days (telephone interview). The primary endpoint was the prevalence of sternal wound infection according to the Centers for Disease Control and Prevention (CDC) criteria. The demographics in both groups were comparable, including age, gender, body mass index, and rate of diabetes and smoking. Sternal wound infection was diagnosed in 43 patients; 23 (12.8%) sutured with triclosan-coated sutures compared to 20 (11.2%) sutured without triclosan (p=0.640). Most infections were superficial (n=36, 10.1%), while 7 (2.0%) were deep sternal wound infections. There were 16 positive cultures in the triclosan group and 17 in the non-coated suture group (p=0.842). The most commonly identified main pathogens were Staphylococcus aureus (45.4%) and coagulase-negative staphylococci (36.4%). Skin closure with triclosan-coated sutures did not reduce the rate of sternal wound infection after coronary artery bypass grafting. (clinicaltrials.gov: NCT01212315).
  •  
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