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- 2019
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Tidskriftsartikel (refereegranskat)
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- Dickie, DA, et al.
(författare)
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Blood pressure variability and leukoaraiosis in acute ischemic stroke
- 2018
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Ingår i: International journal of stroke : official journal of the International Stroke Society. - : SAGE Publications. - 1747-4949. ; 13:5, s. 473-480
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Tidskriftsartikel (refereegranskat)abstract
- Higher blood pressure, blood pressure variability, and leukoaraiosis are risk factors for early adverse events and poor functional outcome after ischemic stroke, but prior studies differed on whether leukoaraiosis was associated with blood pressure variability, including in ischemic stroke. In the Third International Stroke Trial, blood pressure was measured in the acute phase of ischemic stroke immediately prior to randomization, and at 0.5, 1, and 24 h after randomization. Masked neuroradiologists rated index infarct, leukoaraiosis, and atrophy on CT using validated methods. We characterized blood pressure variation by coefficient of variance and three other standard methods. We measured associations between blood pressure, blood pressure variability, and leukoaraiosis using generalized estimating equations, adjusting for age, and a number of covariates related to treatment and stroke type/severity. Among 3017 patients, mean (±SD) systolic and diastolic blood pressure decreased from 155(±24)/82(±15) mmHg pre-randomization to 146(±23)/78(±14) mmHg 24 h later ( P < 0.005). Mean within-subject coefficient of variance was 0.09 ± 0.05 for systolic and 0.11 ± 0.06 for diastolic blood pressure. Patients with most leukoaraiosis were older and had higher blood pressure than those with least ( P < 0.0001). Although statistically significant in simple pairwise comparisons, no measures of blood pressure variability were associated with leukoaraiosis when adjusting for confounding variables ( P > 0.05), e.g. age. Our results suggest that blood pressure variability is not a potential mechanism to explain the association between leukoaraiosis and poor outcome after acute stroke.
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- van Bergen, Jan E. A. M., et al.
(författare)
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Where to go to in chlamydia control? : From infection control towards infectious disease control
- 2021
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Ingår i: Sexually Transmitted Infections. - : BMJ Publishing Group Ltd. - 1368-4973 .- 1472-3263. ; 97:7, s. 501-506
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Forskningsöversikt (refereegranskat)abstract
- Objectives: The clinical and public health relevance of widespread case finding by testing for asymptomatic chlamydia infections is under debate. We wanted to explore future directions for chlamydia control and generate insights that might guide for evidence-based strategies. In particular, we wanted to know the extent to which we should pursue testing for asymptomatic infections at both genital and extragenital sites.Methods: We synthesised findings from published literature and from discussions among national and international chlamydia experts during an invitational workshop. We described changing perceptions in chlamydia control to inform the development of recommendations for future avenues for chlamydia control in the Netherlands.Results: Despite implementing a range of interventions to control chlamydia, there is no practice-based evidence that population prevalence can be reduced by screening programmes or widespread opportunistic testing. There is limited evidence about the beneficial effect of testing on pelvic inflammatory disease prevention. The risk of tubal factor infertility resulting from chlamydia infection is low and evidence on the preventable fraction remains uncertain. Overdiagnosis and overtreatment with antibiotics for self-limiting and non-viable infections have contributed to antimicrobial resistance in other pathogens and may affect oral, anal and genital microbiota. These changing insights could affect the outcome of previous cost-effectiveness analysis.Conclusion: The balance between benefits and harms of widespread testing to detect asymptomatic chlamydia infections is changing. The opinion of our expert group deviates from the existing paradigm of 'test and treat' and suggests that future strategies should reduce, rather than expand, the role of widespread testing for asymptomatic chlamydia infections.
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- Wu, S, et al.
(författare)
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Hyperdense artery sign, symptomatic infarct swelling and effect of alteplase in acute ischaemic stroke
- 2021
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Ingår i: Stroke and vascular neurology. - : BMJ. - 2059-8696 .- 2059-8688. ; 6:2, s. 238-243
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Tidskriftsartikel (refereegranskat)abstract
- Alteplase improves functional outcomes of patients with acute ischaemic stroke, but its effects on symptomatic infarct swelling, an adverse complication of stroke and the influence of CT hyperdense artery sign (HAS) are unclear. This substudy of the Third International Stroke Trial aimed to investigate the association between HAS and symptomatic infarct swelling and effect of intravenous alteplase on this association.MethodsWe included stroke patients whose prerandomisation scan was non-contrast CT. Raters, masked to clinical information, assessed baseline (prerandomisation) and follow-up (24–48 hours postrandomisation) CT scans for HAS, defined as an intracranial artery appearing denser than contralateral arteries. Symptomatic infarct swelling was defined as clinically significant neurological deterioration ≤7 days after stroke with radiological evidence of midline shift, effacement of basal cisterns or uncal herniation.ResultsAmong 2961 patients, HAS presence at baseline was associated with higher risk of symptomatic infarct swelling (OR 2.21; 95% CI 1.42 to 3.44). Alteplase increased the risk of swelling (OR 1.69; 95% CI 1.11 to 2.57), with no difference between patients with and those without baseline HAS (p=0.49). In patients with baseline HAS, alteplase reduced the proportion with HAS at follow-up (OR 0.67; 95% CI 0.50 to 0.91), where HAS disappearance was associated with reduced risk of swelling (OR 0.25, 95% CI 0.14 to 0.47).ConclusionAlthough alteplase was associated with increased risk of symptomatic infarct swelling in patients with or without baseline HAS, it was also associated with accelerated clearance of HAS, which in return reduced swelling, providing further mechanistic insights to underpin the benefits of alteplase.
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- Campbell, M, et al.
(författare)
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Detection of single electrons by means of a Micromegas-covered Medipix2 pixel CMOS readout circuit
- 2005
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Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002 .- 1872-9576. ; 540:2-3, s. 295-304
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Tidskriftsartikel (refereegranskat)abstract
- A small drift chamber was read out by means of a MediPix2 readout chip as a direct anode. A Micromegas foil was placed above the chip, and electron multiplication occurred in the gap. With a He/isobutane 80/20 mixture, gas multiplication factors up to tens of thousands were achieved, resulting in an efficiency for detecting single electrons of better than 90%. We recorded many frames containing 2D images with tracks from cosmic muons. Along these tracks, electron clusters were observed, as well as δ-rays.
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| 11. |
- Colas, P, et al.
(författare)
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The readout of a GEM or Micromegas-equipped TPC by means of the Medipix2 CMOS sensor as direct anode
- 2004
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Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - 0168-9002 .- 1872-9576. ; 535:1-2, s. 506-510
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Tidskriftsartikel (refereegranskat)abstract
- We have applied the Medipix2 pixel CMOS chip as direct anode readout for a TPC. For the gas amplification two options have been investigated: (i) a three-stage GEM system and (ii) a Micromegas mesh. The structure of the cloud of primary electrons, left after interactions of 55Fe quanta with the gas is visible with unprecedented precision. This proof-of-principle is an essential step in our project to realize a monolithic pixel sensor with integrated Micromegas, to be developed specially for the readout of TPCs, and applicable for drift chambers in general.
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- Thalin, C, et al.
(författare)
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Trousseau's Syndrome, a Previously Unrecognized Condition in Acute Ischemic Stroke Associated With Myocardial Injury
- 2014
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Ingår i: Journal of investigative medicine high impact case reports. - : SAGE Publications. - 2324-7096. ; 2:2, s. 2324709614539283-
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Tidskriftsartikel (refereegranskat)abstract
- Trousseau’s syndrome is a well-known malignancy associated hypercoagulative state leading to venous or arterial thrombosis. The pathophysiology is however poorly understood, although multiple mechanisms are believed to be involved. We report a case of Trousseau’s syndrome resulting in concomitant cerebral and myocardial microthrombosis, presenting with acute ischemic stroke and markedly elevated plasma troponin T levels suggesting myocardial injury. Without any previous medical history, the patient developed multiple cerebral infarctions and died within 11 days of admission. The patient was postmortem diagnosed with an advanced metastatic adenocarcinoma of the prostate with disseminated cerebral, pulmonary, and myocardial microthrombosis. Further analyses revealed, to the best of our knowledge for the first time in stroke patients, circulating microvesicles positive for the epithelial tumor marker CK18 and citrullinated histone H3 in thrombi, markers of the recently described cancer-associated procoagulant DNA-based neutrophil extracellular traps. We also found tissue factor, the main in vivo initiator of coagulation, both in thrombi and in metastases. Troponin elevation in acute ischemic stroke is common and has repeatedly been associated with an increased risk of mortality. The underlying pathophysiology is however not fully clarified, although a number of possible explanations have been proposed. We now suggest that unexplainable high levels of troponin in acute ischemic stroke deserve special attention in terms of possible occult malignancy.
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- von Rosen, P, et al.
(författare)
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Menstrual irregularity and use of oral contraceptives in female adolescent athletes in Swedish National Sports High Schools
- 2017
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Ingår i: International journal of adolescent medicine and health. - : Walter de Gruyter GmbH. - 2191-0278. ; 32:2
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Tidskriftsartikel (refereegranskat)abstract
- ObjectiveFemale adolescent athletes seem to use oral contraceptives (OCs) in the same proportion as the general population. In athletes not using OCs, menstrual irregularity (MI) is reported to be common but there are few studies of MI in adolescent athletes. The aim of the study was to survey menarche, menstrual irregularity and use of OCs in adolescent athletes in the National Sports High Schools in Sweden. A further aim was to study the associations between current sport injury and menstrual irregularity as well as use of OCs.SubjectsTwo hundred and ninety-eight female adolescent athletes at Swedish National Sports High Schools.MethodsA web-based questionnaire containing questions related to menstrual status, contraception and current injury.ResultsOne third (32.6%) of the athletes used OCs and of the remaining athletes 31.8% had MI. The group of athletes with MI had a significantly (p = 0.038; Cohen’s d, 0.32) lower BMI and consisted of a significantly (p = 0.043) higher proportion of endurance athletes. OC users were less likely to participate in endurance sports compared to non-OC users (p = 0.024). Current injury was equally distributed in the OC and the non-OC group but athletes with MI had fewer sports injuries compared to eumenorrheic women.ConclusionOCs are frequently used among athletes at Swedish National Sports High Schools. OC users were less likely to participate in endurance sports compared to non-OC users. MI was common and athletes with MI had lower BMI compared to eumenorrheic athletes. Sports injuries were not associated with use of OC and eumenorrheic athletes had a higher proportion of current injury.
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| 23. |
- Vågberg, Mattias, et al.
(författare)
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Guidelines for the use of magnetic resonance imaging in diagnosing and monitoring the treatment of multiple sclerosis: recommendations of the Swedish Multiple Sclerosis Association and the Swedish Neuroradiological Society
- 2017
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Ingår i: Acta Neurologica Scandinavica. - Hoboken, USA : Hindawi Limited. - 0001-6314 .- 1600-0404. ; 135:1, s. 17-24
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Tidskriftsartikel (refereegranskat)abstract
- Multiple sclerosis (MS) is associated with inflammatory lesions in the brain and spinal cord. The detection of such inflammatory lesions using magnetic resonance imaging (MRI) is important in the consideration of the diagnosis and differential diagnoses of MS, as well as in the monitoring of disease activity and predicting treatment efficacy. Although there is strong evidence supporting the use of MRI for both the diagnosis and monitoring of disease activity, there is a lack of evidence regarding which MRI protocols to use, the frequency of examinations, and in what clinical situations to consider MRI examination. A national workshop to discuss these issues was held in Stockholm, Sweden, in August 2015, which resulted in a Swedish consensus statement regarding the use of MRI in the care of individuals with MS. The aim of this consensus statement is to provide practical advice for the use of MRI in this setting. The recommendations are based on a review of relevant literature and the clinical experience of workshop attendees. It is our hope that these recommendations will benefit individuals with MS and guide healthcare professionals responsible for their care.
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- Aufwerber, S, et al.
(författare)
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Does Early Functional Mobilization Affect Long-Term Outcomes After an Achilles Tendon Rupture? A Randomized Clinical Trial
- 2020
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Ingår i: Orthopaedic journal of sports medicine. - : SAGE Publications. - 2325-9671. ; 8:3, s. 2325967120906522-
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Tidskriftsartikel (refereegranskat)abstract
- Functional deficits and health-related impairments are common after an Achilles tendon rupture (ATR). Rehabilitation protocols vary greatly, and few studies have allowed loading in combination with ankle motion immediately after surgery (ie, early functional mobilization [EFM]). It is unclear whether EFM may counteract the negative impact of ankle immobilization after an ATR. Purpose: The primary aim of this study was to assess the efficacy of EFM compared with standard treatment (ie, 2 weeks of unloading in a plaster cast followed by 4 weeks of weightbearing in an orthosis) regarding patient-reported and functional outcomes in patients with an ATR after acute operative repair. The secondary aim was to explore whether the occurrence of deep venous thrombosis (DVT) during the 2 postoperative treatments affected outcomes. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: A total of 135 patients who underwent ATR repair, randomized to either EFM, including immediate postoperative loading and ankle motion, or standard treatment, were evaluated with functional tests and 5 self-administered outcome questionnaires at 6 and 12 months postoperatively. Results: At 6 months, the EFM group scored higher on the RAND 36-Item Health Survey (RAND-36) questionnaire subscales of general health and vitality ( P < .05) compared with the control group. No significant differences between the groups were found on disease-specific questionnaires (Achilles tendon Total Rupture Score [ATRS] and Foot and Ankle Outcome Score [FAOS]). At 12 months, no significant differences on any of the patient-reported outcome measures or the functional heel-rise test were seen between the groups. The RAND-36 subscale of general health, however, exhibited higher values in the EFM group (82.6 ± 16.9) than the control group (77.1 ± 17.0) ( P = .051) at 12 months after the injury. Patients sustaining DVT postoperatively had lower self-reported outcomes on the ATRS, FAOS, and RAND-36 questionnaires at 6 and 12 months compared with patients not having sustained DVT (all P < .05). Conclusion: This study demonstrated that an accelerated postoperative protocol with immediate loading and ankle motion resulted in better general health and vitality at 6 months. However, there were no differences between the groups in the recovery of heel-rise function. Future studies should focus on the means to reduce the risk of DVT to improve patient outcomes after ATR. Registration: NCT02318472 (ClinicalTrials.gov identifier).
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- Aufwerber, S, et al.
(författare)
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High Plantar Force Loading After Achilles Tendon Rupture Repair With Early Functional Mobilization
- 2019
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Ingår i: The American journal of sports medicine. - : SAGE Publications. - 1552-3365 .- 0363-5465. ; 47:4, s. 894-900
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Tidskriftsartikel (refereegranskat)abstract
- Mechanical loading is essential for tendon healing and may explain variability in patient outcomes after Achilles tendon rupture (ATR) repair. However, there is no consensus regarding the optimal postoperative regimen, and the actual amount of loading during orthosis immobilization is unknown. Purpose: The primary aim of this study was to assess the number of steps and the amount of loading in a weightbearing orthosis during the first 6 weeks after surgical ATR repair. A secondary purpose was to investigate if the amount of loading was correlated to fear of movement and/or experience of pain. Study Design: Case series; Level of evidence, 4. Methods: Thirty-four patients (mean ± SD age, 38.8 ± 8.7 years) with ATR repair were included. Early functional mobilization was allowed postoperatively in an orthosis with adjustable ankle range of motion. During the first postoperative 2 weeks, patient-reported loading and pain were assessed with a visual analog scale and step counts with a pedometer. At the 2- and 6-week follow-up, a mobile force sensor was used for measuring plantar force loading, and the Tampa Scale for Kinesiophobia was used to examine fear of movement. Results: Between the first and second weeks, there was a significant increase in the mean number of daily steps taken (from 2025 to 2753, P < .001) as well as an increase in self-reported loading (from 20% to 53%, P < .001). Patient self-reported loading was significantly associated with the plantar force measurement (rho = 0.719, P < .001). At 6 weeks, loading was 88.2% on the injured limb versus the uninjured limb. Fear of movement was not correlated with pedometer data, subjective loading, pain, or force data. Patients with less pain during activity, however, reported significantly higher subjective load and took more steps ( P < .05). Conclusion: This is the first study to demonstrate the actual loading patterns during postoperative functional mobilization among patients with surgically repaired ATR. The quick improvements in loading magnitude and frequency observed may reflect improved tendon loading essential for healing. Pain, rather than fear of movement, was associated with the high variability in loading parameters. The data of this study may be used to improve ATR rehabilitation protocols for future studies. Registration: NCT02318472 (ClinicalTrials.gov).
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- Baeza-Delgado, Carlos, et al.
(författare)
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Biological insertion of computationally designed short transmembrane segments
- 2016
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- The great majority of helical membrane proteins are inserted co-translationally into the ER membrane through a continuous ribosome-translocon channel. The efficiency of membrane insertion depends on transmembrane (TM) helix amino acid composition, the helix length and the position of the amino acids within the helix. In this work, we conducted a computational analysis of the composition and location of amino acids in transmembrane helices found in membrane proteins of known structure to obtain an extensive set of designed polypeptide segments with naturally occurring amino acid distributions. Then, using an in vitro translation system in the presence of biological membranes, we experimentally validated our predictions by analyzing its membrane integration capacity. Coupled with known strategies to control membrane protein topology, these findings may pave the way to de novo membrane protein design.
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- Boekel, Carolina, 1977-
(författare)
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Integration and topology of membrane proteins
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Membrane proteins comprise around 20-30% of most proteomes. They play important roles in most biochemical pathways. All receptors and ion channels are membrane proteins, which make them attractive targets for drug design. Membrane proteins insert and fold co-translationally into the endoplasmic reticular membrane of eukaryotic cells. The protein-conducting channel that inserts the protein into the membrane is called Sec61 translocon, which is a hetero-oligomeric channel that allows transmembrane segments to insert laterally into the lipid bilayer. The focus of this thesis is how the translocon recognizes the transmembrane helices and integrates them into the membrane.We have investigated the sequence requirements for the translocon-mediated integration of a transmembrane α-helix into the ER by challenging the Sec61 translocon with designed polypeptide segments in an in vitro expression system that allows a quantitative assessment of membrane insertion efficiency. Our studies suggest that helices might interact with each other already during the membrane-insertion step, possibly forming helical hairpins that partition into the membrane as a single unit. Further, the insertion efficiency for Nin-Cout vs. Nout-Cin transmembrane helices and the integration efficiency of Alzheimer’s Aβ-peptide fragments has been investigated.Finally, detailed topology mapping was performed on two biologically interesting proteins with unknown topology, the human seipin protein and Drosophila melanogaster odorant receptor OR83b.
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- Emanuelsson, O., von Heijne, G., Elofsson, A., Cristóbal, S.
(författare)
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In silico prediction of the peroxisomal proteome in fungi, plants and animals
- 2003
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Ingår i: J. Mol. Biol.. ; 330, s. 443-456
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Tidskriftsartikel (refereegranskat)abstract
- In an attempt to improve our abilities to predict peroxisomal proteins, we have combined machine-learning techniques for analyzing peroxisomal targeting signals (PTS1) with domain-based cross-species comparisons between eight eukaryotic genomes. Our resul
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- Juncker, Agnieszka S, et al.
(författare)
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Sequence-based feature prediction and annotation of proteins
- 2009
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Ingår i: Genome biology. - : Springer Science and Business Media LLC. - 1465-6914 .- 1465-6906. ; 10:2, s. 206-
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Tidskriftsartikel (refereegranskat)abstract
- A recent trend in computational methods for annotation of protein function is that many prediction tools are combined in complex workflows and pipelines to facilitate the analysis of feature combinations, for example, the entire repertoire of kinase-binding motifs in the human proteome.
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