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Search: WFRF:(Karlström S)

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  • Lundgren, Fredrik, et al. (author)
  • PTFE bypass to below-knee arteries : distal vein collar or not? A prospective randomised multicentre study
  • 2010
  • In: European Journal of Vascular and Endovascular Surgery. - : Elsevier BV. - 1078-5884 .- 1532-2165. ; 39:6, s. 747-754
  • Journal article (peer-reviewed)abstract
    • BackgroundPatency and limb salvage after synthetic bypass to the arteries below-knee are inferior to that which can be achieved with autologous vein. Use of a vein collar at the distal anastomosis has been suggested to improve patency and limb salvage, a problem that is analysed in this randomised clinical study.MethodsPatients with critical limb ischaemia undergoing polytetrafluoroethylene (PTFE) bypass to below-knee arteries were randomly either assigned a vein collar or not in two groups – bypass to the popliteal artery below-knee (femoro-popliteal below-knee (FemPopBK)) and more distal bypass (femoro-distal bypass (FemDist)). Follow-up was scheduled until amputation, death or at most 5 years, whichever event occurred first.ResultsIn the FemPopBK and in the FemDist groups, 115/202 and 72/150 were randomised to have a vein collar, respectively. Information was available for 345 of 352 randomised patients (98%).At 3 years, primary patency was 26% (95% confidence interval (CI) 18–38) with a vein collar and 43 (33–58) without a vein collar for femoro-popliteal bypass and 20 (11–38), and 17 (9–33) for femoro-distal bypass, respectively. The corresponding figures for limb salvage were 64 (54–75) and 61 (50–74) for femoro-popliteal bypass, and 59 (46–76) and 44 (32–61) for femoro-distal bypass with and without a vein collar, respectively. Log-rank-test for the whole Kaplan–Meier life table curve showed no statistically significant differences with or without vein collar primary patency: p = 0.0853, p = 0.228; secondary patency: p = 0.317, p = 0.280; limb salvage: p = 0.757, p = 0.187 for FemPopBK and FemDist, respectively. The use of a vein collar did not influence patency or limb salvage.ConclusionThis study failed to show any benefit for vein collar with PTFE bypass to a below-knee artery.
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  • Zain Elabdien, B S, et al. (author)
  • Rising incidence of hip fracture in Uppsala, 1965-1980
  • 1984
  • In: Acta Orthopaedica Scandinavica. - 0001-6470. ; 55:3, s. 284-89
  • Journal article (peer-reviewed)abstract
    • The frequency and incidence of hip fracture in persons aged 55 years and older in the county of Uppsala during the years 1965, 1970, 1975 and 1980 are reported. For every 5-year interval, the number of hip fractures increased by 21-25 per cent. The ratio of women to men changed from 3.8 in 1965 to 3.1 in 1980. Trochanteric fractures were more common during the later years. The ratio of femoral neck fractures to trochanteric fractures decreased from 1.8 to 1.1 between 1965 and 1980. The incidence of hip fracture in the investigated part of the population increased from 43 per 10 000 in 1965 to 65 in 1980. The age-specific incidence increased especially in the group aged 85 years and older, in which fractures of the femoral neck were three times and trochanteric fractures four times more common in 1980 than in 1965. This investigation shows that the incidence of hip fracture has increased, particularly in the higher age groups. If the age-specific incidences continue to rise in the higher age groups, the frequency of hip fractures will be doubled within a 20-year period.
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  • Abouzayed, Ayman, et al. (author)
  • Preclinical Evaluation of the GRPR-Targeting Antagonist RM26 Conjugated to the Albumin-Binding Domain for GRPR-Targeting Therapy of Cancer
  • 2020
  • In: Pharmaceutics. - : MDPI. - 1999-4923. ; 12:10
  • Journal article (peer-reviewed)abstract
    • The targeting of gastrin-releasing peptide receptors (GRPR) was recently proposed for targeted therapy, e.g., radiotherapy. Multiple and frequent injections of peptide-based therapeutic agents would be required due to rapid blood clearance. By conjugation of the GRPR antagonist RM26 (D-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH2) to an ABD (albumin-binding domain), we aimed to extend the blood circulation of peptides. The synthesized conjugate DOTA-ABD-RM26 was labelled with indium-111 and evaluated in vitro and in vivo. The labelled conjugate was stable in PBS and retained specificity and its antagonistic function against GRPR. The half-maximal inhibitory concentration (IC50) of In-nat-DOTA-ABD-RM26 in the presence of human serum albumin was 49 +/- 5 nM. [In-111]In-DOTA-ABD-RM26 had a significantly longer residence time in blood and in tumors (without a significant decrease of up to 144 h pi) than the parental RM26 peptide. We conclude that the ABD-RM26 conjugate can be used for GRPR-targeted therapy and delivery of cytotoxic drugs. However, the undesirable elevated activity uptake in kidneys abolishes its use for radionuclide therapy. This proof-of-principle study justified further optimization of the molecular design of the ABD-RM26 conjugate.
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  • Arvidsson-Lenner, R, et al. (author)
  • Glycaemic index
  • 2004
  • In: Scandinavian Journal of Food and Nutrition. - : Informa UK Limited. - 1748-2976. ; 48:2, s. 84-94
  • Journal article (peer-reviewed)abstract
    • The glycaemic index (GI) concept is based on the difference in blood glucose response after ingestion of the same amount of carbohydrates from different foods, and possible implications of these differences for health, performance and well-being. GI is defined as the incremental blood glucose area (0-2 h) following ingestion of 50 g of available carbohydrates in the test product as a percentage of the corresponding area following an equivalent amount of carbohydrate from a reference product. A high GI is generally accompanied by a high insulin response. The glycaemic load (GL) is the GI×the amount (g) of carbohydrate in the food/100. Many factors affect the GI of foods, and GI values in published tables are indicative only, and cannot be applied directly to individual foods. Properly determined GI values for individual foods have been used successfully to predict the glycaemic response of a meal, while table values have not. An internationally recognised method for GI determination is available, and work is in progress to improve inter- and intra-laboratory performance. Some epidemiological studies and intervention studies indicate that low GI diets may favourably influence the risk of chronic diseases such as diabetes and coronary heart disease, although further well-controlled studies are needed for more definite conclusions. Low GI diets have been demonstrated to improve the blood glucose control, LDL-cholesterol and a risk factor for thrombosis in intervention studies with diabetes patients, but the effect in free-living conditions remains to be shown. The impact of GI in weight reduction and maintenance as well as exercise performance also needs further investigation. The GI concept should be applied only to foods providing at least 15 g and preferably 20 g of available carbohydrates per normal serving, and comparisons should be kept within the same food group. For healthy people, the significance of GI is still unclear and general labelling is therefore not recommended. If introduced, labelling should be product-specific and considered on a case-by-case basis.
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  • Carlbring, Per, et al. (author)
  • Internet-Delivered Attention Training for SAD : who Responds and Why
  • 2014
  • In: Abstracts from the 48th Annual Convention of the Association for Behavioral and Cognitive Therapies.
  • Conference paper (other academic/artistic)abstract
    • While attention modification programs (AMP) have shown promise as laboratory-based treatments for social anxiety disorder, trials of internet-delivered AMP have not yielded significant differences between active and control conditions. To address these inconsistencies, we examined the moderational and mediational role of attention bias in the efficacy of attention training. We compared data reported by Carlbring et al. (2012) to an identical AMP condition, with the exception that participants were instructed to activate social anxiety fears prior to each attention training session (AMP+FACT; n=39). We also compared all attention training groups to an internet-delivered cognitive-behavioral therapy (iCBT) condition (n=40). Participants in the AMP+FACT group experienced greater reductions in social anxiety symptoms than both active (n=40) and control (n=39) groups reported by Carlbring et al., and did not differ in symptom reductions from the iCBT group. Higher attention bias predicted greater symptom reductions for participants who completed AMP, but not for the control group. Moreover, change in attention bias mediated the relationship between AMP group (active condition reported by Carlbring et al. versus AMP+FACT) and change in social anxiety symptoms. These results suggest the importance of interpreting findings related to symptom change in attention training studies in the context of bias effects.
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  • Cavallaro, Sara, et al. (author)
  • Label-Free Surface Protein Profiling of Extracellular Vesicles by an Electrokinetic Sensor
  • 2019
  • In: ACS Sensors. - : AMER CHEMICAL SOC. - 2379-3694. ; 4:5, s. 1399-1408
  • Journal article (peer-reviewed)abstract
    • Small extracellular vesicles (sEVs) generated from the endolysosomal system, often referred to as exosomes, have attracted interest as a suitable biomarker for cancer diagnostics, as they carry valuable biological information and reflect their cells of origin. Herein, we propose a simple and inexpensive electrical method for label-free detection and profiling of sEVs in the size range of exosomes. The detection method is based on the electrokinetic principle, where the change in the streaming current is monitored as the surface markers of the sEVs interact with the affinity reagents immobilized on the inner surface of a silica microcapillary. As a proof-of-concept, we detected sEVs derived from the non-small-cell lung cancer (NSCLC) cell line H1975 for a set of representative surface markers, such as epidermal growth factor receptor (EGFR), CD9, and CD63. The detection sensitivity was estimated to be similar to 175000 sEVs, which represents a sensor surface coverage of only 0.04%. We further validated the ability of the sensor to measure the expression level of a membrane protein by using sEVs displaying artificially altered expressions of EGFR and CD63, which were derived from NSCLC and human embryonic kidney (HEK) 293T cells, respectively. The analysis revealed that the changes in EGFR and CD63 expressions in sEVs can be detected with a sensitivity in the order of 10% and 3%, respectively, of their parental cell expressions. The method can be easily parallelized and combined with existing microfluidic-based EV isolation technologies, allowing for rapid detection and monitoring of sEVs for cancer diagnosis.
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  • Dharmowijoyo, Bayu Endrayana, et al. (author)
  • Collecting a multi-dimensional three-weeks household time-use and activity diary in the Bandung Metropolitan Area, Indonesia
  • 2015
  • In: Transportation Research Part A. - : Elsevier. - 0965-8564 .- 1879-2375. ; 80, s. 231-246
  • Journal article (peer-reviewed)abstract
    • This paper describes a comprehensive panel data collection and analysis at household level, including detailed travel behaviour variables and comprehensive in-home and out-of-home activities, individual cognitive habits and affective behaviours, the rate of physical activity, as well as health related quality of life (QoL) information in the Bandung Metropolitan Area (BMA) of Indonesia. To our knowledge, this is the first attempt to collect an individual's activity diary over an extended period as it captures the multi-tasking activities and multidisciplinary factors that underlie individual activity-travel patterns in a developing country. Preliminary analyses of the collected data indicate that different beliefs, anticipated emotions, support and attachment to motorised modes significantly correlate with different groups of occupation, gender, age, activity participation, multi-tasking activities, and physical health, but not with different social and mental health. This finding highlights the reason why implementing car reduction policies in Indonesia, without breaking or changing the individual's habits and influencing his/her attitudes have not been fruitful. The results also show that endorsing more physical activities may result in a significant reduction in the individual's motorised mode use, whilst individuals who demonstrate a tendency to use their spare time on social activities tend to have better social health conditions. Furthermore, undertaking multi-tasking out-of-home discretionary activities positively correlates with better physical health. All these highlight the importance of properly understanding and analysing the complex mechanisms that underlie these fundamental factors that shape individual daily activity-travel patterns in developing countries. This type of multidisciplinary approach is needed to design better transport policies that will not only promote better transport conditions, but also a healthier society with a better quality of life.
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  • Hagberg, Daniel, et al. (author)
  • On the solvation of ions in small water droplets
  • 2005
  • In: The Journal of Physical Chemistry Part B. - : American Chemical Society (ACS). - 1520-5207 .- 1520-6106. ; 109:9, s. 4111-4117
  • Journal article (peer-reviewed)abstract
    • The solvations of positively and negatively charged model ions in water droplets have been studied using Monte Carlo simulations performed with a polarizable intermolecular potential function model. Special focus has been placed on the position of the ion in the water droplet. It was found that the sign of the ionic charge is of minor importance but an increased ionic charge localizes the ion to the central regions of the droplet, whereas a large polarizability and a large ionic radius favor locations close to the surface of the water droplet.
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  • Hermida-Ramon, J M, et al. (author)
  • Inter- and intramolecular potential for the N-formylglycinamide-water system. A comparison between theoretical modeling and empirical force fields
  • 2003
  • In: Journal of Computational Chemistry. - : Wiley. - 1096-987X .- 0192-8651. ; 24:2, s. 161-176
  • Journal article (peer-reviewed)abstract
    • An intramolecular NEMO potential is presented for the N-formylglycinamide molecule together with an intermolecular potential for the N-formylglycinamide-water system. The intramolecular N-formylglycinamide potential can be used as a building block for the backbone of polypeptides and proteins. Two intramolecular minima have been obtained. One, denoted as C5, is stabilized by a hydrogen bonded five member ring, and the other, denoted as C7, corresponds to a seven membered ring. The interaction between one water molecule and the N-formylglycinamide system is also studied and compared with Hartree-Fock SCF calculations and with the results obtained for some of the more commonly used force fields. The agreement between the NEMO and SCF energies for the complexes is in general superior to that of the other force fields. In the C7 region the surfaces obtained from the intramolecular part of the commonly used force fields are too flat compared to the NEMO potential and the ab initio calculations. We further analyze the possibility of using a charge distribution obtained from one conformation to describe the charge distribution of other conformations. We have found that the use of polarizabilities and generic dipoles can model most of the changes in charge density due to the different geometry of the new conformations, but that one can expect additional errors in the interaction energies that are of the order of 1 kcal/mol. © 2002 Wiley Periodicals, Inc. J Comput Chem 24: 161-176, 2003
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  • Karlström, Daniel, et al. (author)
  • A minimal test practice framework for emerging software organizations
  • 2005
  • In: Software Testing, Verification & Reliability. - : Wiley. - 0960-0833 .- 1099-1689. ; 15:3, s. 145-166
  • Journal article (peer-reviewed)abstract
    • Testing takes a large share of software development efforts, and hence is of interest when seeking improvements. Several test process improvement frameworks exist, but they are extensive and much too large to be effective for smaller organizations. This paper presents a minimal test practice framework (MTPF) that allows the incremental introduction of appropriate practices at the appropriate time in rapidly expanding organizations. The process for introducing the practice framework tries to minimize resistance to change by maximizing the involvement of the entire organization in the improvement effort and ensuring that changes are made in small steps with a low threshold for each step. The practice framework created and its method of introduction have been evaluated at one company by applying the framework for a one-year period. Twelve local software development companies have also evaluated the framework in a survey.
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  • Kirsanskas, Gediminas, et al. (author)
  • Thermopower signatures and spectroscopy of the canyon of conductance suppression
  • 2016
  • In: Physical Review B. - 1098-0121. ; 94:4
  • Journal article (peer-reviewed)abstract
    • Interference effects in quantum dots between different transport channels can lead to a strong suppression of conductance, which cuts like a canyon through the common conductance plot [Phys. Rev. Lett. 104, 186804 (2010)PRLTAO0031-900710.1103/PhysRevLett.104.186804]. In the present work we consider the thermoelectric transport properties of the canyon of conductance suppression using the second-order von Neumann approach. We observe a characteristic signal for the zeros of the thermopower. This demonstrates that thermoelectric measurements are an interesting complimentary tool to study complex phenomena for transport through confined systems.
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  • Koochek, Afsaneh, et al. (author)
  • Dietary differences between elderly Iranians living in Sweden and Iran a cross-sectional comparative study
  • 2011
  • In: BMC Public Health. - : Springer Science and Business Media LLC. - 1471-2458. ; 11, s. 411-
  • Journal article (peer-reviewed)abstract
    • Background: During the last decades, global migration has increased and many immigrant groups have a higher prevalence than the native born population of several cardiovascular disease risk factors, including poor dietary habits. However, it is uncertain if dietary habits in immigrant populations reflect dietary habits in their country of origin or if the current diet is a consequence of the migration and possible change of dietary habits. The aim of this study was to examine possible dietary differences between elderly Iranians living in Stockholm, Sweden with elderly Iranians living in Tehran, Iran, taking into account sex, age, marital status, and education. Methods: Dietary intakes were assessed by semi - quantitative food frequency questionnaire in a cross-sectional study of 121 Iranians living in Stockholm and 52 Iranians living in Tehran, aged 60-80. Differences in dietary habits between the two groups was analysed by bootstrapped regression analyses with 1000 replications. Results: Iranians living in Sweden had significantly higher intake of protein, total fat, fiber than Iranians living in Iran, but lower consumption of carbohydrates. The observed differences in intake of macronutrients were reflected in consumed amount of all food items, which were higher among Iranians living in Iran with the exception of bread and grain consumption which was lower. Conclusions: There are general differences in dietary habits between Iranians living in Iran and Iranians living in Sweden. Parts of observed differences in dietary habits may reflect a favourable adoption process to the Swedish dietary habits after migration. Meanwhile other differences are point of concern in light of the high prevalence of overweight, among Iranians living in Sweden and can have unfavourable impact in particular in the context of cardiovascular health.
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  • Lindgren, Joel, et al. (author)
  • Engineered non-fluorescent Affibody molecules facilitate studies of the amyloid-beta (A beta) peptide in monomeric form : Low pH was found to reduce A beta/Cu(II) binding affinity
  • 2013
  • In: Journal of Inorganic Biochemistry. - : Elsevier BV. - 0162-0134 .- 1873-3344. ; 120, s. 18-23
  • Journal article (peer-reviewed)abstract
    • Aggregation of amyloid-beta (A beta) peptides into oligomers and amyloid plaques in the human brain is considered a causative factor in Alzheimer's disease (AD). As metal ions are over-represented in AD patient brains, and as distinct A beta aggregation pathways in presence of Cu(II) have been demonstrated, metal binding to A beta likely affects AD progression. A beta aggregation is moreover pH-dependent, and AD appears to involve inflammatory conditions leading to physiological acidosis. Although metal binding specificity to A beta varies at different pH's, metal binding affinity to A beta has so far not been quantitatively investigated at sub-neutral pH levels. This may be explained by the difficulties involved in studying monomeric peptide properties under aggregation-promoting conditions. We have recently devised a modified Affibody molecule, Z(A beta 3)(12-58), that binds A beta with sub-nanomolar affinity, thereby locking the peptide in monomeric form without affecting the N-terminal region where metal ions bind. Here, we introduce non-fluorescent A beta-binding Affibody variants that keep A beta monomeric while only slightly affecting the A beta peptide's metal binding properties. Using fluorescence spectroscopy, we demonstrate that Cu(II)/A beta(1-40) binding is almost two orders of magnitude weaker at pH 5.0 (apparent K-D = 51 mu M) than at pH 7.3 (apparent K-D = 0.86 mu M). This effect is arguably caused by protonation of the histidines involved in the metal ligandation. Our results indicate that engineered variants of Affibody molecules are useful for studying metal-binding and other properties of monomeric A beta under various physiological conditions, which will improve our understanding of the molecular mechanisms involved in AD.
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  • Lindgren, Joel, et al. (author)
  • N-terminal engineering of amyloid-beta-binding Affibody molecules yields improved chemical synthesis and higher binding affinity
  • 2010
  • In: Protein Science. - : Wiley. - 0961-8368 .- 1469-896X. ; 19:12, s. 2319-2329
  • Journal article (peer-reviewed)abstract
    • The aggregation of amyloid-beta (A beta) peptides is believed to be a major factor in the onset and progression of Alzheimer's disease Molecules binding with high affinity and selectivity to A beta-peptides are important tools for investigating the aggregation process An A beta-binding Affibody molecule, Z(A beta 3), has earlier been selected by phage display and shown to bind A beta(1-40) with nanomolar affinity and to inhibit A beta-peptide aggregation In this study, we create truncated functional versions of the Z(A beta 3) Affibody molecule better suited for chemical synthesis production Engineered Affibody molecules of different length were produced by solid phase peptide synthesis and allowed to form covalently linked homodimers by S-S-bridges The N-terminally truncated Affibody molecules Z(A beta 3)(12-58), Z(A beta 3)(15-58), and Z(A beta 3)(18-58) were produced in considerably higher synthetic yield than the corresponding full-length molecule Z(A beta 3)(1-58) Circular dichroism spectroscopy and surface plasmon resonance-based biosensor analysis showed that the shortest Affibody molecule, Z(A beta 3)(18-58), exhibited complete loss of binding to the A beta(1-40)-peptide, while the Z(A beta 3)(12-58) and Z(A beta 3)(15-58) Affibody molecules both displayed approximately one order of magnitude higher binding affinity to the A beta(1-40)-peptide compared to the full-length Affibody molecule Nuclear magnetic resonance spectroscopy showed that the structure of A beta(1-40) in complex with the truncated Affibody dimers is very similar to the previously published solution structure of the A beta(1-40)-peptide in complex with the full-length Z(A beta 3) Affibody molecule This indicates that the N-terminally truncated Affibody molecules Z(A beta 3)(12-58) and Z(A beta 3)(15-58) are highly promising for further engineering and future use as binding agents to monomeric A beta(1-40)
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  • Lindgren, Joel, et al. (author)
  • N-terminal engineering of amyloid-β-binding Affibody molecules yields improved chemical synthesis and higher binding affinity
  • 2010
  • In: Protein Science. - : Wiley. - 0961-8368 .- 1469-896X. ; 19:12, s. 2319-2329
  • Journal article (peer-reviewed)abstract
    • The aggregation of amyloid-beta (A beta) peptides is believed to be a major factor in the onset and progression of Alzheimer's disease Molecules binding with high affinity and selectivity to A beta-peptides are important tools for investigating the aggregation process An A beta-binding Affibody molecule, Z(A beta 3), has earlier been selected by phage display and shown to bind A beta(1-40) with nanomolar affinity and to inhibit A beta-peptide aggregation In this study, we create truncated functional versions of the Z(A beta 3) Affibody molecule better suited for chemical synthesis production Engineered Affibody molecules of different length were produced by solid phase peptide synthesis and allowed to form covalently linked homodimers by S-S-bridges The N-terminally truncated Affibody molecules Z(A beta 3)(12-58), Z(A beta 3)(15-58), and Z(A beta 3)(18-58) were produced in considerably higher synthetic yield than the corresponding full-length molecule Z(A beta 3)(1-58) Circular dichroism spectroscopy and surface plasmon resonance-based biosensor analysis showed that the shortest Affibody molecule, Z(A beta 3)(18-58), exhibited complete loss of binding to the A beta(1-40)-peptide, while the Z(A beta 3)(12-58) and Z(A beta 3)(15-58) Affibody molecules both displayed approximately one order of magnitude higher binding affinity to the A beta(1-40)-peptide compared to the full-length Affibody molecule Nuclear magnetic resonance spectroscopy showed that the structure of A beta(1-40) in complex with the truncated Affibody dimers is very similar to the previously published solution structure of the A beta(1-40)-peptide in complex with the full-length Z(A beta 3) Affibody molecule This indicates that the N-terminally truncated Affibody molecules Z(A beta 3)(12-58) and Z(A beta 3)(15-58) are highly promising for further engineering and future use as binding agents to monomeric A beta(1-40)
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  • Panda, S., et al. (author)
  • Factors influencing decision-making for caesarean section in Sweden - a qualitative study
  • 2018
  • In: Bmc Pregnancy and Childbirth. - : Springer Science and Business Media LLC. - 1471-2393. ; 18
  • Journal article (peer-reviewed)abstract
    • Background: Rising rates of caesarean section (CS) are a concern in many countries, yet Sweden has managed to maintain low CS rates. Exploring the multifactorial and complex reasons behind the rising trend in CS has become an important goal for health professionals. The aim of the study was to explore Swedish obstetricians' and midwives' perceptions of the factors influencing decision-making for CS in nulliparous women in Sweden. Methods: A qualitative design was chosen to gain in-depth understanding of the factors influencing the decision-making process for CS. Purposive sampling was used to select the participants. Four audio-recorded focus group interviews (FGIs), using an interview guide with open ended questions, were conducted with eleven midwives and five obstetricians from two selected Swedish maternity hospitals after obtaining written consent from each participant. Data were managed using NVivo (c) and thematically analysed. Ethical approval was granted by Trinity College Dublin. Results: The thematic analysis resulted in three main themes; 'Belief in normal birth - a cultural perspective'; 'Clarity and consistency - a system perspective' and 'Obstetrician makes the final decision, but ...', and each theme contained a number of subthemes. However, 'Belief in normal birth' emerged as the core central theme, overarching the other two themes. Conclusion: Findings suggest that believing that normal birth offers women and babies the best possible outcome contributes to having and maintaining a low CS rate. Both midwives and obstetricians agreed that having a shared belief (in normal birth), a common goal (of achieving normal birth) and providing mainly midwife-led care within a 'team approach' helped them achieve their goal and keep their CS rate low.
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  • Sahu, Siddharth S., et al. (author)
  • Electrokinetic sandwich assay and DNA mediated charge amplification for enhanced sensitivity and specificity
  • 2021
  • In: Biosensors & bioelectronics. - : Elsevier BV. - 0956-5663 .- 1873-4235. ; 176
  • Journal article (peer-reviewed)abstract
    • An electrical immuno-sandwich assay utilizing an electrokinetic-based streaming current method for signal transduction is proposed. The method records the changes in streaming current, first when a target molecule binds to the capture probes immobilized on the inner surface of a silica micro-capillary, and then when the detection probes interact with the bound target molecules on the surface. The difference in signals in these two steps constitute the response of the assay, which offers better target selectivity and a linear concentration dependent response for a target concentration within the range 0.2-100 nM. The proof of concept is demonstrated by detecting different concentrations of Immunoglobulin G (IgG) in both phosphate buffered saline (PBS) and spiked in E. coli cell lysate. A superior target specificity for the sandwich assay compared to the corresponding direct assay is demonstrated along with a limit of detection of 90 pM in PBS. The prospect of improving the detection sensitivity was theoretically analysed, which indicated that the charge contrast between the target and the detection probe plays a crucial role in determining the signal. This aspect was then experimentally validated by modulating the zeta potential of the detection probe by conjugating negatively charged DNA oligonucleotides. The length of the conjugated DNA was varied from 5 to 30 nucleotides, altering the zeta potential of the detection probe from -9.3 +/- 0.8 mV to -20.1 +/- 0.9 mV. The measurements showed a clear and consistent enhancement of detection signal as a function of DNA lengths. The results presented here conclusively demonstrate the role of electric charge in detection sensitivity as well as the prospect for further improvement. The study therefore is a step forward in developing highly selective and sensitive electrokinetic assays for possible application in clinical investigations.
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  • Sahu, Siddharth S., et al. (author)
  • Exploiting Electrostatic Interaction for Highly Sensitive Detection of Tumor-Derived Extracellular Vesicles by an Electrokinetic Sensor
  • 2021
  • In: ACS Applied Materials and Interfaces. - : American Chemical Society (ACS). - 1944-8244 .- 1944-8252. ; 13:36, s. 42513-42521
  • Journal article (peer-reviewed)abstract
    • We present an approach to improve the detection sensitivity of a streaming current-based biosensor for membrane protein profiling of small extracellular vesicles (sEVs). The experimental approach, supported by theoretical investigation, exploits electrostatic charge contrast between the sensor surface and target analytes to enhance the detection sensitivity. We first demonstrate the feasibility of the approach using different chemical functionalization schemes to modulate the zeta potential of the sensor surface in a range -16.0 to -32.8 mV. Thereafter, we examine the sensitivity of the sensor surface across this range of zeta potential to determine the optimal functionalization scheme. The limit of detection (LOD) varied by 2 orders of magnitude across this range, reaching a value of 4.9 x 10(6) particles/mL for the best performing surface for CD9. We then used the optimized surface to profile CD9, EGFR, and PD-L1 surface proteins of sEVs derived from non-small cell lung cancer (NSCLC) cell-line H1975, before and after treatment with EGFR tyrosine kinase inhibitors, as well as sEVs derived from pleural effusion fluid of NSCLC adenocarcinoma patients. Our results show the feasibility to monitor CD9, EGFR, and PD-L1 expression on the sEV surface, illustrating a good prospect of the method for clinical application.
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  • Sahu, Siddharth S., et al. (author)
  • Multi-marker profiling of extracellular vesicles using streaming current and sequential electrostatic labeling
  • 2023
  • In: Biosensors & bioelectronics. - : Elsevier BV. - 0956-5663 .- 1873-4235. ; 227
  • Journal article (peer-reviewed)abstract
    • High heterogeneity in the membrane protein expression of small extracellular vesicles (sEVs) means that bulk methods relying on antibody-based capture for expression analysis have a drawback that each type of antibody may capture a different sub-population. An improved approach is to capture a representative sEV population, without any bias, and then perform a multiplexed protein expression analysis on this population. However, such a possibility has been largely limited to fluorescence-based methods. Here, we present a novel electrostatic labelling strategy and a microchip-based all-electric method for membrane protein analysis of sEVs. The method allows us to profile multiple surface proteins on the captured sEVs using alternating charge labels. It also permits the comparison of expression levels in different sEV-subtypes. The proof of concept was tested by capturing sEVs both non-specifically (unbiased) as well as via anti-CD9 capture probes (biased), and then profiling the expression levels of various surface proteins using the charge labelled antibodies. The method is the first of its kind, demonstrating an all-electrical and microchip based method that allows for unbiased analysis of sEV membrane protein expression, comparison of expression levels in different sEV subsets, and fractional estimation of different sEV sub-populations. These results were also validated in parallel using a single-sEV fluorescence technique.
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  • Svensson, Per-Arne, 1969, et al. (author)
  • Urokinase-type plasminogen activator receptor is associated with macrophages and plaque rupture in symptomatic carotid atherosclerosis.
  • 2008
  • In: International journal of molecular medicine. - : Spandidos Publications. - 1107-3756. ; 22:4, s. 459-64
  • Journal article (peer-reviewed)abstract
    • There is a strong correlation between macrophage infiltration and plaque instability in recently symptomatic carotid atherosclerotic plaques, and it is hypothesised that mechanisms related to macrophages may be involved in plaque vulnerability and rupture. We previously found high expression of urokinase-type plasminogen activator receptor (UPAR) in human macrophages. The aim of this study was to investigate whether UPAR co-localises with macrophages in symptomatic carotid plaques, and whether UPAR expression is associated with plaque rupture. Real-time RT-PCR assays showed that UPAR expression levels were high in monocyte-derived macrophages and in carotid endarterectomies compared with a tissue panel. Serial transverse sections were prepared from carotid endarterectomies from 12 symptomatic patients, and analyzed with immunohistochemical staining for UPAR and for CD68-positive macrophages, and with histopathological assessment. UPAR co-localised with CD68-positive macrophages, with a high correlation (r=0.90, p<0.001) between immunostained areas in 12 carotid endarterectomies from symptomatic patients. High degrees of UPAR and CD68 staining were found in sections around the bifurcation level where rupture was most common, while low degrees of staining were found in sections of the common carotid artery end of the endarterectomy (p<0.05). Higher degrees of UPAR staining were observed in ruptured plaque sections compared with non-ruptured sections. In conclusion, UPAR was highly expressed in monocyte-derived macrophages and in symptomatic carotid plaques, UPAR co-localised with macrophages in carotid symptomatic plaques and UPAR was predominantly found in ruptured plaque segments. These findings support the hypothesis that UPAR is related to plaque rupture in symptomatic atherosclerotic lesions.
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36.
  • Sydsjö, Gunilla, et al. (author)
  • Personality characteristics in a Swedish national sample of identifiable oocyte donors
  • 2011
  • In: British Journal of Obstetrics and Gynecology. - : Wiley. - 1470-0328 .- 1471-0528. ; 118:9, s. 1067-1072
  • Journal article (peer-reviewed)abstract
    • Objective To study the personality characteristics of identifiable oocyte donors in a national sample in comparison with normal values. Design Descriptive study. Setting All Swedish donation programmes. Sample In total, 181 women out of 221 donors recruited during 2005-2008. Methods Standardised questionnaires were used to measure personality characteristics. Main outcome measure Demographics, temperament and character inventory (TCI). Results The majority (69%) of the donors had biological children of their own. The results from the TCI indicate that the oocyte donors were all within the normal range of character. With regard to personality, a significant difference was evident between the two groups: oocyte donors showed lower means for harm avoidance and higher scores for persistence than the controls. This indicates that the donors felt less worried, and displayed a lower level of fear of uncertainty, shyness and fatiguability, and a higher level of persistence, than the controls. In the present sample, 29 (16%) of the donors were so-called 'known donors', that is the recipient couples and the donors were known to each other. 'Known donors' displayed a mature and stable character. Conclusion We found that the women who had been accepted for inclusion in this nationwide oocyte donor programme were all well adjusted and mature.
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37.
  • Tiiman, Ann, et al. (author)
  • Specific Binding of Cu(II) Ions to Amyloid-Beta Peptides Bound to Aggregation-Inhibiting Molecules or SDS Micelles Creates Complexes that Generate Radical Oxygen Species
  • 2016
  • In: Journal of Alzheimer's Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 54:3, s. 971-982
  • Journal article (peer-reviewed)abstract
    • Aggregation of the amyloid-beta (A beta) peptide into insoluble plaques is a major factor in Alzheimer's disease (AD) pathology. Another major factor in AD is arguably metal ions, as metal dyshomeostasis is observed in AD patients, metal ions modulate A beta aggregation, and AD plaques contain numerous metals including redox-active Cu and Fe ions. In vivo, A beta is found in various cellular locations including membranes. So far, Cu(II)/A beta interactions and ROS generation have not been investigated in a membrane environment. Here, we study Cu(II) and Zn(II) interactions with A beta bound to SDS micelles or to engineered aggregation-inhibiting molecules (the cyclic peptide CP-2 and the Z(A beta 3)(12-58) Y18L Affibody molecule). In all studied systems the A beta N-terminal segment was found to be unbound, unstructured, and free to bind metal ions. In SDS micelles, A beta was found to bind Cu(II) and Zn(II) with the same ligands and the same K-D as in aqueous solution. ROS was generated in all Cu(II)/A beta complexes. These results indicate that binding of A beta to membranes, drugs, and other entities that do not interact with the A beta N-terminal part, appears not to compromise the N-terminal segment's ability to bind metal ions, nor impede the capacity of N-terminally bound Cu(II) to generate ROS.
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38.
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39.
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40.
  • Waters, S, et al. (author)
  • Effects of pretreatment with a xanthine oxidase inhibitor on free radical levels during carotid endarterectomy.
  • 2004
  • In: Free Radic Res. - : Informa UK Limited. - 1071-5762 .- 1029-2470. ; 38:3, s. 283-293
  • Journal article (peer-reviewed)abstract
    • Objective: Free radicals contribute to the tissue damage caused by ischaemia-reperfusion. The aim of the present study was to investigate whether preoperative antioxidant therapy (allopurinol) affects free radical levels in cerebral venous blood in connection with surgery for carotid artery stenosis. Materials and methods: Twenty-five patients were randomised into the study. Thirteen were controls and 12 were pretreated with allopurinol the day before surgery. Before, during and after surgery, blood samples were drawn from the ipsilateral jugular vein. Radical levels were measured using the spin trap technique ex vivo using OXANOH as the spin trap. Multivariate statistics were used with Principal Component Analysis and Partial Least Square regression analysis. Results: Radical levels increased with diabetes, high leukocyte count, high creatinine and a high degree of contralateral stenosis. Radical levels decreased with high age, blood pressure, collateral circulation as well as operation for left-side carotid artery stenosis. After pretreatment with allopurinol, several of the relationships noted in the control group were eliminated, i.e. leukocyte count, side of operation, Betapred pretreatment and collateral circulation. Conclusions: Radical levels can be determined in connection with surgery for carotid artery stenosis using an ex vivo spin trap method. With preoperative antioxidant therapy the relationships between enhanced radical levels and clinical data, as seen in control subjects, disappeared. This might indicate a beneficial effect of preoperative pretreatment with antioxidants.
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41.
  • Wikland, Matts, et al. (author)
  • A randomized controlled study comparing pain experience between a newly designed needle with a thin tip and a standard needle for oocyte aspiration
  • 2011
  • In: Human Reproduction. - : Oxford University Press (OUP). - 0268-1161 .- 1460-2350. ; 26:6 (Jun), s. 1377-83
  • Journal article (peer-reviewed)abstract
    • BACKGROUND Ultrasound-guided transvaginal oocyte retrieval is often performed under local anaesthesia on an outpatient basis. The objective of this study was to compare the overall pain experience of a newly designed reduced needle (RN) compared with a thicker standard needle (SN). METHODS A prospective, randomized, multi-centre study was performed at four different clinics from June to December 2009. The oocyte aspiration was performed under local anaesthesia, either with a needle with a reduced diameter (0.9 mm) for the last 50 mm from the tip (RN) or with a SN (1.4 mm). A total of 257 patients were randomized (RN: n = 129; SN: n = 128). The primary endpoint was the overall pain experience self-assessed and registered by the patient on a visual analogue scale (VAS 0 mm = no pain to 100 mm = unbearable pain) immediately after the oocyte retrieval. Secondary end-points such as vaginal bleeding and several embryological parameters were also registered. RESULTS The overall pain during the oocyte retrieval procedure was significantly lower in the RN group than in the SN group (mean 21.0 mm, SD 17.5 mm and median 19.0 mm versus mean 26.0 mm, SD 19.9 mm and median 24.0 mm; P = 0.040, difference between groups mean−5.0 mm, 95% CI: 9.7 to−0.4). This was also true when adjusting for baseline characteristics such as number of follicles, number of previous oocyte pick-up, body mass index and age, by a multiple linear regression analysis. Significantly more patients (40 of 126) had less than expected vaginal bleeding in the RN group when compared with the SN group (24 of 124; 32 versus 19%; P = 0.03 and 95% CI 1.7–23.0%). No differences were found between the two needles with regard to additional i.v. analgesia, aspiration time, oocyte recovery, fertilization, cleavage rate, number of good quality embryos, number of embryos for freezing and pregnancy rate. CONCLUSIONS Oocyte aspiration performed with the newly designed thinner-tipped needle resulted in significantly less overall pain and less vaginal bleeding, without prolonging the retrieval procedure or influence the oocyte recovery rate, when compared with a SN. Clinicaltrials.gov: NCT00924885
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