| 1. |
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| 2. |
- Siegel, G., et al.
(författare)
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Lipoprotein binding to anionic biopolyelectrolytes and the effect of glucose on nanoplaque formation in arteriosclerosis and Alzheimer's disease
- 2016
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Ingår i: Advances in Colloid and Interface Science. - : Elsevier BV. - 0001-8686 .- 1873-3727. ; 232, s. 25-35
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Tidskriftsartikel (refereegranskat)abstract
- Arteriosclerosis with its clinical sequelae (cardiac infarction, stroke, peripheral arterial occlusive disease) and vascular/Alzheimer dementia not only result in far more than half of all deaths but also represent dramatic economic problems. The reason is, among others, that diabetes mellitus is an independent risk factor for both disorders, and the number of diabetics strongly increases worldwide. More than one-half of infants in the first 6 months of life have already small collections of macrophages and macrophages filled with lipid droplets in susceptible segments of the coronary arteries. On the other hand, the authors of the Bogalusa Heart Study found a strong increase in the prevalence of obesity in childhood that is paralleled by an increase in blood pressure, blood lipid concentration, and type 2 diabetes mellitus. Thus, there is a clear linkage between arteriosclerosis/Alzheimer's disease on the one hand and diabetes mellitus on the other hand. Furthermore, it has been demonstrated that distinct apoE isoforms on the blood lipids further both arteriosclerotic and Alzheimer nanoplaque formation and therefore impair flow-mediated vascular reactivity as well. Nanoplaque build-up seems to be the starting point for arteriosclerosis and Alzheimer's disease in their later full clinical manifestation. In earlier work, we could portray the anionic biopolyelectrolytes syndecan/perlecan as blood flow sensors and lipoprotein receptors in cell membrane and vascular matrix. We described extensively molecular composition, conformation, form and function of the macromolecule heparan sulfate proteoglycan (HS-PG). In two supplementary experimental settings (ellipsometry, myography), we utilized isolated HS-PG for in vitro nanoplaque investigations and isolated human coronary artery segments for in vivo tension measurements. With the ellipsometry-based approach, we were successful in establishing a direct connection on a molecular level between diabetes mellitus on the one side and arteriosclerosis/Alzheimer's disease on the other side. Application of glucose at a concentration representative for diabetics and leading to glycation of proteins and lipids, entailed a significant increase in arteriosclerotic and Alzheimer nanoplaque formation. IDLapoE4/E4 was by far superior to IDLapoE3/E3 in plaque build-up, both in diabetic and non-diabetic patients. Recording vascular tension of flow-dependent reactivity in blood substitute solution and under application of different IDLapoE isoforms showed an impaired vasorelaxation for pooled IDL and IDLapoE4/E4, thus confirming the ellipsometric investigations. Incubation in IDLapoE0/E0 (apoE "knockout man"), however, resulted in a massive flow mediated contraction, also complemented" by strongly aggregated nanoplaques. In contrast, HDL was shown to present a powerful protection against nanoplaque formation on principle, both in the in vitro model and the in vivo scenario on the endothelial cell membrane. The competitive interplay with LDL is highlighted through the flow experiment, where flow-mediated, HDL-induced vasodilatation remains untouched by additional incubation with LDL. This is due to the four times higher affinity for the proteoglycan receptor of HDL as compared to LDL. Taken together, the studies demonstrate that while simplistic, the ellipsometry approach and the endothelial mimicking proteoglycan-modified surfaces provide information on the initial steps of lipoprotein-related plaque formation, which correlates with findings on endothelial cells and blood vessels, and afford insight into the role of lipoprotein deposition and exchange phenomena at the onset of these pathophysiologies.
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| 3. |
- Dias, R, et al.
(författare)
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DNA-lipid systems. A physical chemistry study
- 2002
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Ingår i: Brazilian Journal of Medical and Biological Research. - 0100-879X. ; 35:5, s. 509-522
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Tidskriftsartikel (refereegranskat)abstract
- It is well known that the interaction of polyelectrolytes with oppositely charged surfactants leads to an associative phase separation; however, the phase behavior of DNA and oppositely charged surfactants is more strongly associative than observed in other systems. A precipitate is formed with very low amounts of surfactant and DNA. DNA compaction is a general phenomenon in the presence of multivalent ions and positively charged surfaces; because of the high charge density there are strong attractive ion correlation effects. Techniques like phase diagram determinations, fluorescence microscopy, and ellipsometry were used to study these systems. The interaction between DNA and catanionic mixtures (i.e., mixtures of cationic and anionic surfactants) was also investigated. We observed that DNA compacts and adsorbs onto the surface of positively charged vesicles, and that the addition of an anionic surfactant can release DNA back into solution from a compact globular complex between DNA and the cationic surfactant. Finally, DNA interactions with polycations, chitosans with different chain lengths, were studied by fluorescence microscopy, in vivo transfection assays and cryogenic transmission electron microscopy. The general conclusion is that a chitosan effective in promoting compaction is also efficient in transfection.
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| 4. |
- Généreux, Philippe, et al.
(författare)
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Evolution and Prognostic Impact of Cardiac Damage After Aortic Valve Replacement.
- 2022
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Ingår i: Journal of the American College of Cardiology. - 1558-3597.
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Tidskriftsartikel (refereegranskat)abstract
- The impact of aortic valve replacement (AVR) on progression/regression of extra-valvular cardiac damage and its association with subsequent prognosis is unknown.To describe evolution of cardiac damage post-AVR and its association with outcomes.Patients undergoing transcatheter or surgical AVR from the PARTNER 2 and 3 trials were pooled and classified by cardiac damage stage at baseline and 1-year (Stage 0, no damage; Stage 1, left ventricular damage; Stage 2, left atrial or mitral valve damage; Stage 3, pulmonary vasculature or tricuspid valve damage; Stage 4, right ventricular damage). Proportional hazards models determined association between change in cardiac damage post-AVR and 2-year outcomes.Among 1974 patients, 121 (6.1%) were Stage 0, 287 (14.5%) Stage 1, 1014 (51.4%) Stage 2, 412 (20.9%) Stage 3, and 140 (7.1%) Stage 4 pre-AVR. Two-year mortality was associated with extent of cardiac damage at baseline and 1-year. Compared with baseline, cardiac damage improved in ∼15%, remained unchanged in ∼60%, and worsened in ∼25% of patients at 1-year. One-year change in cardiac damage stage was independently associated with mortality (adjHR for improvement=0.49; no change=1.0; worsening=1.95; p=0.023) and composite of death or heart failure hospitalization (adjHR for improvement=0.60; no change=1.0; worsening=2.25; p<0.001) at 2 years.In patients undergoing AVR, extent of extravalvular cardiac damage at baseline and its change at 1-year have important prognostic implications. These findings suggest that earlier detection of AS and intervention prior to development of irreversible cardiac damage may improve global cardiac function and prognosis.
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| 5. |
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| 6. |
- Siegel, Günter, et al.
(författare)
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Flow sensing in the cardiovascular system
- 2015
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Ingår i: Colloids and Surfaces A. - : Elsevier BV. - 0927-7757 .- 1873-4359. ; 480, s. 318-327
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Tidskriftsartikel (refereegranskat)abstract
- Background: This contribution deals with chemical processes at the biological membranes of endothelial cells in blood vessels. A basic observation is that the intensity of blood flow navigates the vascular width through a negative feedback circle. When the blood flow increases, the vessels become wider; when it decreases the vascular smooth muscle cells contract. The anionic polyelectrolyte heparan sulfate proteoglycan (HS-PG) reacts to the shear stress generated by the flowing blood. In the present investigation, this naturally occurring biosensor is characterized in more detail, which is crucially involved in the regulation of peripheral blood flow and organ perfusion. A dysfunction of this sensor can lead to organ insufficiency, hypertension and arteriosclerosis.
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| 7. |
- Wilking, N., et al.
(författare)
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Long-term follow-up of the SBG 9401 study comparing tailored FEC-based therapy versus marrow-supported high-dose therapy
- 2007
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Ingår i: Annals of Oncology. - : Elsevier BV. - 0923-7534 .- 1569-8041. ; 18:4, s. 694-700
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Tidskriftsartikel (refereegranskat)abstract
- Background: The purpose was to investigate adjuvant marrow-supportive high-dose chemotherapy compared with an equitoxicity-tailored comparator arm. Patients and methods: Five hundred and twenty-five women below theage of 60 years with operated high-risk primary breast cancer were randomised to nine cycles of granulocyte colony-stimulating factor supported and individually tailored FEC (5-fluorouracil, epirubicin, cyclophosphamide), (n = 251) or standard FEC followed by marrow-supported high-dose therapy with CTCb (cyclophosphamide, thiotepa, carboplatin) therapy (n = 274), followed by locoregional radiotherapy and tamoxifen for 5 years. Results: There were 104 breast cancer relapses in the tailored FEC group versus 139 in the CTCb group (double triangular method by Whitehead, P = 0.046), with a median follow-up of all included patients of 60.8 months. The event-free survival demonstrated 121 and 150 events in the tailored FEC- and CTCb group, respectively [P = 0.074, hazard ratio (HR) 0.804, 95% confidence interval (CI) 0.633-1.022]. Ten patients in the tailored FEC regimen developed acute myeloid leukaemia (AML)/myelodysplasia (MDS). One hundred deaths occurred in the tailored FEC group and 121 in the CTCb group (P = 0.287, HR 0.866, 95% CI 0.665-1.129). Conclusion: The update of this study shows an improved outcome linked to the tailored FEC treatment in relation to breast cancer relapse, but also an increased incidence of AML/MDS. © 2007 Oxford University Press.
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| 8. |
- Öhlin, Axel, 1990, et al.
(författare)
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Protocol for a multicenter prospective cohort study evaluating arthroscopic and non-surgical treatment for microinstability of the hip joint
- 2022
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Ingår i: BMC Musculoskeletal Disorders. - : Springer Science and Business Media LLC. - 1471-2474. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Microinstability of the hip joint is a proposed cause of hip pain and reduced function in young individuals. The underlying mechanism is thought to be extraphysiological hip motion due to bony deficiency and/or soft tissue deficiency or decreased soft tissue function. Recently, the condition has gained increased attention, and despite the fact that treatment today includes both non-surgical and surgical approaches, there is limited evidence on diagnostic specificity and treatment effects. The aim of this study is to evaluate clinical outcomes of both nonsurgical and surgical treatment for microinstability of the hip joint. Methods: A multicenter prospective cohort study is planned to evaluating the outcome of physical therapy aimed at stabilizing the hip joint, as well as arthroscopic plication of the hip joint capsule, if the physical therapy fails. Outcomes will be evaluated using hip-specific patient-reported outcome measures: the short version of the International Hip Outcome Tool and the Copenhagen Hip and Groin Outcome Score, strength and function tests, health-related quality of life as determined using the European Quality of Life-5 Dimensions and the European Quality of Life-Visual Analog Scale, sports activity levels according to the Hip Sport Activity Scale, and reported complications. Patients will be evaluated at 6, 12 and 24 months after each treatment. Discussion: It is important to evaluate the clinical outcomes of both non-surgical and surgical treatment for suspected microinstability of the hip joint, and the planned prospective evaluation will contribute to the understanding of non-surgical as well as surgical treatment outcomes, including complications.
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| 9. |
- Antunes, Filipe, et al.
(författare)
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Network formation of catanionic vesicles and oppositely charged polyelectrolytes. Effect of polymer charge density and hydrophobic modification
- 2004
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Ingår i: Langmuir. - : American Chemical Society (ACS). - 0743-7463 .- 1520-5827. ; 20:11, s. 4647-4656
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Tidskriftsartikel (refereegranskat)abstract
- In nonequimolar solutions of a cationic and an anionic surfactant, vesicles bearing a net charge can be spontaneously formed and apparently exist as thermodynamically stable aggregates. These vesicles can associate strongly with polymers in solution by means of hydrophobic and/or electrostatic interactions. In the current work, we have investigated the rheological and microstructural properties of mixtures of cationic polyelectrolytes and net anionic sodium dodecyl sulfate/didodecyldimethylammonium bromide vesicles. The polyelectrolytes consist of two cationic cellulose derivatives with different charge densities; the lowest charge density polymer contains also hydrophobic grafts, with the number of charges equal to the number of grafts. For both systems, polymer-vesicle association leads to a major increase in viscosity and to gel-like behavior, but the viscosity effects are more pronounced for the less charged, hydrophobically modified polymer. Evaluation of the frequency dependence of the storage and loss moduli for the two systems shows further differences in behavior: while the more long-lived cross-links occur for the more highly charged hydrophilic polymer, the number of cross-links is higher for the hydrophobically modified polymer. Microstructure studies by cryogenic transmission electron microscopy indicate that the two polymers affect the vesicle stability in different ways. With the hydrophobically modified polymer, the aggregates remain largely in the form of globular vesicles and faceted vesicles (polygon-shaped vesicles with largely planar regions). For the hydrophilic polycation, on the other hand, the surfactant aggregate structure is more extensively modified: first, the vesicles change from a globular to a faceted shape; second, there is opening of the bilayers leading to holey vesicles and ultimately to considerable vesicle disruption leading to planar bilayer, disklike aggregates. The faceted shape is tentatively attributed to a crystallization of the surfactant film in the vesicles. It is inferred that a hydrophobically modified polyion with relatively low charge density can better stabilize vesicles due to formation of molecularly mixed aggregates, while a hydrophilic polyion with relatively high charge density associates so strongly to the surfactant films, due to strong electrostatic interactions, that the vesicles are more perturbed and even disrupted.
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| 10. |
- Campion, James, 1989-, et al.
(författare)
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Toward Industrial Exploitation of THz Frequencies : Integration of SiGe MMICs in Silicon-Micromachined Waveguide Systems
- 2019
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Ingår i: IEEE Transactions on Terahertz Science and Technology. - : Institute of Electrical and Electronics Engineers (IEEE). - 2156-342X .- 2156-3446. ; 9:6, s. 624-636
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Tidskriftsartikel (refereegranskat)abstract
- A new integration concept for terahertz (THz) systems is presented in this article, wherein patterned silicon-on-insulator wafers form all DC, IF, and RF networks in a homogeneous medium, in contrast to existing solutions. Using this concept, silicon-micromachined waveguides are combined with silicon germanium (SiGe) monolithic microwave integrated circuits (MMICs) for the first time. All features of the integration platform lie in the waveguide’s H-plane. Heterogeneous integration of SiGe chips is achieved using a novel in-line H-plane transition. As an initial step toward complete systems, we outline the design, fabrication, and assembly of back-to-back transition structures, for use at D-band frequencies (110ï¿œ170 GHz). Special focus is given to the industrial compatibility of all components, fabrication, and assembly processes, with an eye on the future commercialization of THz systems. Prototype devices are assembled via two distinct processes, one of which utilizes semiautomated die-bonding tools. Positional and orientation tolerances for each process are quantified. An accuracy of $\pm \text3.5\; μ \textm$, $\pm \text1.5 °$ is achieved. Measured $S$-parameters for each device are presented. The insertion loss of a single-ended transition, largely due to MMIC substrate losses, is 4.2ï¿œ5.5 dB, with a bandwidth of 25 GHz (135ï¿œ160 GHz). Return loss is in excess of 5 dB. Measurements confirm the excellent repeatability of the fabrication and assembly processes and, thus, their suitability for use in high-volume applications. The proposed integration concept is highly scalable, permitting its usage far into the THz frequency spectrum. This article represents the first stage in the shift to highly compact, low-cost, volume-manufacturable THz waveguide systems.
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| 11. |
- Cárdenas, Marité, et al.
(författare)
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DNA compaction onto hydrophobic surfaces by different cationic surfactants
- 2005
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Ingår i: Langmuir. - : American Chemical Society (ACS). - 0743-7463 .- 1520-5827. ; 21:14, s. 6495-6502
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Tidskriftsartikel (refereegranskat)abstract
- DNA compaction by alkyltrimethylammonium surfactants at hydrophobized silica surfaces and the effect of the counterion, as well as the hydrocarbon chain length, was investigated by in situ null-ellipsometry. In addition, DNA compaction in the presence of a gemini surfactant, hexyl-alpha,omega-bis(dodecyldimethylammonium bromide), was studied. The type of cationic amphiphile used was found not to have a pronounced effect on the mixed DNA-cationic surfactant adsorbed layer thickness, although the surface concentration excess for the mixed layers seemed to follow the same trend as that for DNA-free surfactant layers. Interestingly, it was also found that the stability of the mixed adsorbed layer largely depends on the cationic surfactant used.
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| 12. |
- Carter, Jodi M., et al.
(författare)
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Distinct spatial immune microlandscapes are independently associated with outcomes in triple-negative breast cancer
- 2023
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- The utility of spatial immunobiomarker quantitation in prognostication and therapeutic prediction is actively being investigated in triple-negative breast cancer (TNBC). Here, with high-plex quantitative digital spatial profiling, we map and quantitate intraepithelial and adjacent stromal tumor immune protein microenvironments in systemic treatment-naive (female only) TNBC to assess the spatial context in immunobiomarker-based prediction of outcome. Immune protein profiles of CD45-rich and CD68-rich stromal microenvironments differ significantly. While they typically mirror adjacent, intraepithelial microenvironments, this is not uniformly true. In two TNBC cohorts, intraepithelial CD40 or HLA-DR enrichment associates with better outcomes, independently of stromal immune protein profiles or stromal TILs and other established prognostic variables. In contrast, intraepithelial or stromal microenvironment enrichment with IDO1 associates with improved survival irrespective of its spatial location. Antigen-presenting and T-cell activation states are inferred from eigenprotein scores. Such scores within the intraepithelial compartment interact with PD-L1 and IDO1 in ways that suggest prognostic and/or therapeutic potential. This characterization of the intrinsic spatial immunobiology of treatment-naive TNBC highlights the importance of spatial microenvironments for biomarker quantitation to resolve intrinsic prognostic and predictive immune features and ultimately inform therapeutic strategies for clinically actionable immune biomarkers.
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| 13. |
- Dias, Rita, et al.
(författare)
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Electrophoretic properties of complexes between DNA and the cationic surfactant cetyltrimethylammonium bromide
- 2005
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Ingår i: Electrophoresis. - : Wiley. - 0173-0835 .- 1522-2683. ; 26:15, s. 2908-2917
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Tidskriftsartikel (refereegranskat)abstract
- We use agarose gel electrophoresis to characterize how the monovalent catioinic surfactant cetyltrimethylammonium bromide (CTAB) compacts double-stranded DNA, which is detected as a reduction in electrophoretic DNA velocity. The velocity reaches a plateau at a ratio R = 1.8 of CTAB to DNA-phosphate charges, i.e., above the neutralization point, and the complexes retain a net negative charge at least up to R = 200. Condensation experiments on a mixture of two DNA sizes show that the complexes formed contain only one condensed DNA molecule each. These CTAB-DNA globules were further characterized by time-resolved measurements of their velocity inside the gel, which showed that CTAB does not dissociate during the migration but possibly upon entry into the gel. Using the Ogston-model for electrophoresis of spherical particles, the measured in-gel velocity of the globule is quantitatively consistent with CTAB having two opposite effects, reduction of both the electrophoretic charge and DNA coll size. In the case of CTAB the two effects nearly cancel, which can explain why opposite velocity shifts (globule faster than uncomplexed DNA) have been observed with some catioinic condensation agents. Dissociation of the complexes by addition of anionic surfactants was also studied. The DNA release from the globule was complete at a mixing ratio between anionic and cationic surfactants equal to 1, in agreement with equilibrium studies. Circular DNA retained its supercoiling, and this demonstrates a lack of DNA nicking in the compaction-release cycle which is important in DNA transfection and purification applications.
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| 14. |
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| 15. |
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| 16. |
- Généreux, Philippe, et al.
(författare)
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Design and Rationale of the Evaluation of Transcatheter Aortic Valve Replacement Compared to SurveilLance for Patients with AsYmptomatic Severe Aortic Stenosis: The EARLY TAVR Trial.
- 2024
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Ingår i: American heart journal. - 1097-6744. ; 268, s. 94-103
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Tidskriftsartikel (refereegranskat)abstract
- For patients with asymptomatic, severe aortic stenosis (AS) and preserved left ventricular ejection fraction, current guidelines recommend clinical surveillance every 6 to 12 months. To date, no randomized trials have examined whether an early intervention with transcatheter aortic valve replacement (TAVR) will improve outcomes among these patients.EARLY TAVR is a prospective, randomized, controlled, multicenter trial, with an event-based design. Asymptomatic severe AS patients (n=900) are randomized 1:1 to either clinical surveillance or TAVR with the Edwards SAPIEN 3/SAPIEN 3 Ultra transcatheter heart valve. Patients are stratified by whether they are able to perform a treadmill stress test. The primary endpoint is death, stroke, or unplanned cardiovascular hospitalization. Patients who are asymptomatic but have a positive stress test will be followed in a registry and undergo aortic valve replacement as per current guidelines.EARLY TAVR is the largest randomized trial to date assessing the role of early intervention among patients with asymptomatic severe AS compared to clinical surveillance, and the first to study the role of TAVR.NCT03042104.
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| 17. |
- Hahn, Rebecca T, et al.
(författare)
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Tricuspid Valve Academic Research Consortium Definitions for Tricuspid Regurgitation and Trial Endpoints.
- 2023
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Ingår i: Journal of the American College of Cardiology. - 1558-3597.
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Tidskriftsartikel (refereegranskat)abstract
- Interest in the pathophysiology, etiology, management, and outcomes of patients with tricuspid regurgitation (TR) has grown in the wake of multiple natural history studies showing progressively worse outcomes associated with increasing TR severity, even after adjusting for multiple comorbidities. Historically, isolated tricuspid valve surgery has been associated with high in-hospital mortality rates, leading to the development of transcatheter treatment options. The aim of this first Tricuspid Valve Academic Research Consortium document is to standardize definitions of disease etiology and severity, as well as endpoints for trials that aim to address the gaps in our knowledge related to identification and management of patients with TR. Standardizing endpoints for trials should provide consistency and enable meaningful comparisons between clinical trials. A second Tricuspid Valve Academic Research Consortium document will focus on further defining trial endpoints and will discuss trial design options.
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| 18. |
- Hahn, Rebecca T, et al.
(författare)
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Tricuspid Valve Academic Research Consortium Definitions for Tricuspid Regurgitation and Trial Endpoints.
- 2023
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Ingår i: The Annals of thoracic surgery. - 1552-6259.
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Tidskriftsartikel (refereegranskat)abstract
- Interest in the pathophysiology, etiology, management, and outcomes of patients with tricuspid regurgitation (TR) has grown in the wake of multiple natural history studies showing progressively worse outcomes associated with increasing TR severity, even after adjusting for multiple comorbidities. Historically, isolated tricuspid valve surgery has been associated with high in-hospital mortality rates, leading to the development of transcatheter treatment options. The aim of this first Tricuspid Valve Academic Research Consortium document is to standardize definitions of disease etiology and severity, as well as endpoints for trials that aim to address the gaps in our knowledge related to identification and management of patients with TR. Standardizing endpoints for trials should provide consistency and enable meaningful comparisons between clinical trials. A second Tricuspid Valve Academic Research Consortium document will focus on further defining trial endpoints and will discuss trial design options.
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| 19. |
- Hahn, Rebecca T, et al.
(författare)
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Tricuspid Valve Academic Research Consortium Definitions for Tricuspid Regurgitation and Trial Endpoints.
- 2023
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Ingår i: European heart journal. - 1522-9645.
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Tidskriftsartikel (refereegranskat)abstract
- Interest in the pathophysiology, etiology, management, and outcomes of patients with tricuspid regurgitation (TR) has grown in the wake of multiple natural history studies showing progressively worse outcomes associated with increasing TR severity, even after adjusting for multiple comorbidities. Historically, isolated tricuspid valve surgery has been associated with high in-hospital mortality rates, leading to the development of transcatheter treatment options. The aim of this first Tricuspid Valve Academic Research Consortium document is to standardize definitions of disease etiology and severity, as well as endpoints for trials that aim to address the gaps in our knowledge related to identification and management of patients with TR. Standardizing endpoints for trials should provide consistency and enable meaningful comparisons between clinical trials. A second Tricuspid Valve Academic Research Consortium document will focus on further defining trial endpoints and will discuss trial design options.
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| 20. |
- Ivanova, R, et al.
(författare)
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Effect of pharmaceutically acceptable glycols on the stability of the liquid crystalline gels formed by poloxamer 407 in water
- 2002
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Ingår i: Journal of Colloid and Interface Science. - : Elsevier BV. - 1095-7103 .- 0021-9797. ; 252:1, s. 226-235
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Tidskriftsartikel (refereegranskat)abstract
- The ability of poly(ethylene oxide)-poly(propylene oxide)-poly (ethylene oxide) (PEO-PPO-PEO) block copolymers (Poloxamers) to form "gels" (lyotropic liquid crystalline structures) in water is of interest to pharmaceutical applications. In such applications the presence of polar organic solvents is often desirable or required. The effect of such solvents on the stability of lyotropic liquid crystalline gels formed by PEO-PPO-PEO block copolymers was assessed by studying the phase behavior and structure in ternary isothermal (25degreesC) systems of pharmaceutical interest consisting of Poloxamer 407 (EO100PO70EO100), water, and one of the following solvents (referred to here collectively as "glycols"): glycerol, propylene glycol, ethanol, polyethylene glycol 400, and glucose. Small-angle X-ray scattering was employed to establish the structure of the liquid crystals obtained and to determine their characteristic length scales. The stability range of the liquid crystalline gel phases in the systems studied was found to vary with the glycol type. For example, the micellar cubic structure can accommodate about 0.85:1 parts glucose per part water (in terms of weight) and up to as much as 5.5:1 parts propylene glycol per part water. A correlation between the glycol effects on the stability of the liquid crystalline phases and glycol physiochemical characteristics such as octanol/water partition coefficient or solubility parameter is proposed.
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| 21. |
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| 22. |
- Karpati, F, et al.
(författare)
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Arbitrarily primed PCR and sequencing of 16S rDNA for epidemiological typing and species identification of Burkholderia cepacia isolates from Swedish patients with cystic fibrosis reveal genetic heterogeneity
- 2001
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Ingår i: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS). - 0903-4641 .- 1600-0463. ; 109:5, s. 389-400
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Tidskriftsartikel (refereegranskat)abstract
- To investigate whether arbitrarily primed (AP)-PCR and/or 16S rDNA sequencing could be used as rapid methods for epidemiological typing and species identification of clinical Burkholderia isolates from patients with cystic fibrosis (CF), a total of 39 clinical B. cepacia isolates, including 33 isolates from 14 CF patients, were fingerprinted. ERIC-2 primer was used for AP-PCR. The AP-PCR clustering analysis resulted in 14 different clusters at a 70% similarity level. The AP-PRC patterns were individual despite considerable similarities. To sequence rDNA, a broad-range PCR was applied. The PCR product included four variable loops (V8, V3, V4 and V9) of the 16S ribosomal small subunit RNA gene. The multiple sequence alignment produced 12 different patterns, 5 of them including more than one isolate. Heterogeneity of the bases in the V3 region, indicating the simultaneous presence of at least two different types of 16S rRNA genes in the same cell, was revealed in 10 isolates. Most of the CF patients were adults who had advanced disease at follow-up. Both the sequencing and the AP-PCR patterns revealed genetic heterogeneity of isolates between patients. According to the results obtained, AP-PCR could advantageously be used for epidemiological typing of Burkholderia, whereas partial species identification could effectively be obtained by sequencing of the V3 region of the 16S RNA gene.
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| 23. |
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| 24. |
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| 25. |
- Larsson, Britt, et al.
(författare)
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Fibre type proportion and fibre size in trapezius muscle biopsies from cleaners with and without myalgia and its correlation with ragged red fibres, cytochrome-c-oxidase-negative fibres, biomechanical output, perception of fatigue, and surface electromyography during repetitive forward flexions
- 2001
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Ingår i: European Journal of Applied Physiology. - : Springer Science and Business Media LLC. - 1439-6327 .- 1439-6319. ; 84:6, s. 492-502
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Tidskriftsartikel (refereegranskat)abstract
- In the literature enlarged/increased cross-sectional area (CSA) of type I muscle fibres has been reported as a morphological mark of work-related localised myalgia in the descending part of the trapezius muscle of women. These studies did not use enough subjects or lacked an adequate control group. The recording of surface electromyograms (EMG) is central to the research field of work-related myalgia. However, the influence of intrinsic muscle properties such as the effect of muscle fibre distribution upon surface EMG has to be better understood in order properly to evaluate this method as a possible diagnostic and preventive tool. This study had two aims. Firstly, it investigated the muscle fibre distribution and CSA in work-related myalgia in trapezius muscles. Secondly, the multivariate relationships among muscle morphology and histochemistry [ragged-red (RR) fibres, and cytochrome-c-oxidase-negative-fibre changes] EMG, perceived fatigue, and biomechanical output of shoulder flexions were analysed. The raw data have been presented in an earlier study. The participants in this study were 25 female cleaners with work-related myalgia of the trapezius muscle and 25 female cleaners not experiencing work-related myalgia of this muscle. The control group comprised 21 healthy female teachers who had not been exposed to highly repetitive work or static muscle work. Smaller CSA of type II fibres were found in cleaners compared to teachers. In this study the CSA of type I fibres of the trapezius muscles associated with myalgia were no greater than in muscles without myalgia. The prevalence of RR fibres together with age, fibre type proportions, CSA and working as a cleaner correlated with the ability to relax as recorded electromyographically. The relative mean frequency of the EMG of the trapezius muscle correlated with the prevalence of RR fibres, but it did not correlate with the proportions and CSA of different fibre types. Low biomechanical outputs and low signal amplitude increases of the EMG during the test were associated with high proportions of type -IIB fibres. The smaller CSA of type II fibres in cleaners might have reflected a different muscle activation pattern due to different occupational demands in cleaners than in teachers. Morphological or histopathological variables can influence the three EMG variables investigated.
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| 26. |
- Larsson, Britt, et al.
(författare)
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The prevalences of cytochrome c oxidase negative and superpositive fibres and ragged-red fibres in the trapezius muscle of female cleaners with and without myalgia and of female healthy controls
- 2000
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Ingår i: Pain. - 1872-6623 .- 0304-3959. ; 84:2-3, s. 379-387
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Tidskriftsartikel (refereegranskat)abstract
- The association of cytochrome c oxidase negative fibres (COX-negative) and ragged-red fibres (RR-fibres) with work related trapezius myalgia has been proposed. Hitherto studies have been small or without control groups. The aim of the present study was to investigate the prevalences of RR-fibres and COX-negative fibres in female cleaners with (n=25) and without (n=23) trapezius myalgia and in clinically healthy female teachers (n=21). The cleaners did mainly floor cleaning requiring monotonous loading on the trapezius muscle. A questionnaire covering background data and aspects of pain (prevalence, duration, intensity and influence on daily living) was answered. Biopsies were obtained from the trapezius muscle by an open surgical technique. The three groups did not differ in prevalence of COX-negative or COX-superpositive (i.e. type-I fibres with extremely strong brownish reaction in both the COX and SDH/COX stainings) fibres. The prevalence of COX-negative fibres was age dependent. Two subgroups of RR-fibres were present when stained for COX; COX-negative (73%) and COX-superpositive (26%) fibres. Forty-two percent of the COX-negative fibres were RR-fibres and 79% of the COX-superpositive were RR-fibres. A significantly (P=0.002) higher proportion of the COX-superpositive fibres in the cleaners were RR-fibres compared to the teachers. Multivariate regression analysis revealed that age, occupation as cleaner and a tender point in the trapezius were significantly associated with increased prevalences of RR-fibres; a cleaner with a tender point had a 4.35 higher prevalence of RR-fibres compared to a teacher without a tender point. No correlations between other pain related variables and prevalence of RR-fibres were noted. In conclusion, RR-fibres but not COX-negative or COX-superpositive fibres were correlated with cleaning work tasks and with a tender point in the trapezius.
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| 27. |
- Li, Y., et al.
(författare)
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D-band SiGe transceiver modules based on silicon-micromachined integration
- 2019
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Ingår i: Asia-Pacific Microwave Conference Proceedings, APMC. - : Institute of Electrical and Electronics Engineers (IEEE). ; 2019-December, s. 883-885
-
Konferensbidrag (refereegranskat)abstract
- This paper reports on 130 GHz transceiver modules consisting of integrated multi-functional chipsets in a commercial 130nm SiGe BiCMOS process. The interconnect between the chipset and the package is non-galvanic and is realized in silicon micromachining technique. After successful fabrication and assembly, the individual Tx and Rx modules as well as the combined Tx-Rx link were tested using CW signals. Then realtime data transport over the link were carried out using different modulation formats and bandwidths. With 16QAM over a 750 MHz channel a 2.66 Gbit/s data rate was demonstrated with BER<10-11. These tests show that the D-band modules, obtained in a single implementation trial, work well functionally. The interconnect method is applicable to the full D-band and expected to also support frequencies in the sub-millimeter-wave range where traditional methods become challenging to apply.
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| 28. |
- Lindman, Björn, et al.
(författare)
-
DNA-lipid systems. An amphiphile self-assembly and polymer-surfactant perspective
- 2002
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Ingår i: Lipid and Polymer-Lipid Systems. - Berlin, Heidelberg : Springer Berlin Heidelberg. - 0340-255X .- 1437-8027. - 9783540430018 ; 120, s. 52-63
-
Konferensbidrag (refereegranskat)abstract
- The interaction between DNA and oppositely charged surfactants has been investigated by several techniques, like fluorescence microscopy, electron microscopy, phase diagram determination, and ellipsometry. The phase behaviour is more strongly associative than that in previously studied systems. A precipitate is formed for very low amounts of surfactant and DNA. DNA compaction is a general phenomenon in the presence of multivalent ions and positively charged surfaces; because of the high charge density there are strong attractive ion correlation effects. The interaction between DNA and catanionic mixtures (i.e., mixtures of cationic and anionic surfactants) was also investigated. We observed that DNA compacts and adsorbs onto the surface of positively charged vesicles and that the addition of anionic surfactant can release free DNA back into solution from a compact globular complex between DNA and cationic surfactant. Finally, we investigated DNA interactions with polycations, chitosans with different chain lengths, by fluorescence microscopy, in vivo transfections assays and cryogenic transmission electron microscopy. The general conclusion is that a chitosan effective in promoting compaction is also efficient in transfection.
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| 29. |
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| 30. |
- Lindman, Ida, et al.
(författare)
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Five-Year Outcomes After Arthroscopic Surgery for Femoroacetabular Impingement Syndrome in Elite Athletes
- 2020
-
Ingår i: American Journal of Sports Medicine. - : SAGE Publications. - 0363-5465 .- 1552-3365. ; 48:6, s. 1416-1422
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Tidskriftsartikel (refereegranskat)abstract
- © 2020 The Author(s). Background: Femoroacetabular impingement syndrome (FAIS) is a common cause of hip pain and disability in athletes. Arthroscopic treatment for FAIS is well-established; however, the long-term results in elite athletes are limited. Purpose: To evaluate outcomes 5 years after arthroscopic treatment for FAIS in elite athletes. Study Design: Case series; Level of evidence, 4. Methods: Elite athletes undergoing arthroscopic treatment for FAIS with a minimum 5-year follow-up were included. They were prospectively followed up with patient-reported outcome measures. An elite athlete was defined as having a Hip Sports Activity Scale (HSAS) level of 7 or 8 before the onset of symptoms. Preoperatively and 5 years after surgery, all athletes completed a web-based questionnaire, including the Copenhagen Hip and Groin Outcome Score (comprising 6 subscales), the EQ-5D and EQ-VAS (European Quality of Life–5 Dimensions Questionnaire and European Quality of Life–Visual Analog Scale), iHOT-12 (International Hip Outcome Tool), a visual analog scale for hip function, and the HSAS. Moreover, patients reported their overall satisfaction with their hip function. Preoperative measurements were compared with the 5-year follow-up. Results: A total of 64 elite athletes (52 men, 12 women) with a mean ± SD age of 24 ± 6 years were included. On average, patients reported a statistically significant and clinically relevant improvement from preoperative patient-reported outcome measures to the 5-year follow-up (P <.0003), Copenhagen Hip and Groin Outcome Score subscales (symptoms, 51.7 vs 71.9; pain, 61.0 vs 81.1; function of daily living, 67.1 vs 83.6; function in sports and recreation, 40.0 vs 71.5; participation in physical activity, 25.0 vs 67.4; hip and groin–related quality of life, 34.4 vs 68.0), EQ-5D (0.60 vs 0.83), EQ-VAS (66.1 vs 76.7), and iHOT-12 (40.0 vs 68.8). At the 5-year follow-up, 90.5% reported satisfaction with their overall hip function. In total, 54% still participated in competitive sports (HSAS, 5-8) at follow-up, while 77% had decreased their level. Older patients and patients with longer duration of symptoms reported a significantly lower level of sports activity (HSAS, 0-4; P <.009). Conclusion: Arthroscopic treatment for FAIS in elite athletes results in a statistically significant and clinically relevant improvement regarding symptoms, hip function, quality of life, and pain 5 years after surgery. Approximately half of the cohort was still in competitive sports at follow-up, yet 77% had decreased their level of sports. Nine of 10 patients were satisfied with their surgery.
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| 31. |
- Lindman, Ida, et al.
(författare)
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Improvements After Arthroscopic Treatment for Femoroacetabular Impingement Syndrome in High-Level Ice Hockey Players : 2-Year Outcomes by Player Position
- 2021
-
Ingår i: Orthopaedic Journal of Sports Medicine. - : SAGE Publications. - 2325-9671. ; 9:3
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Ice hockey players often undergo arthroscopic treatment for femoroacetabular impingement syndrome (FAIS); however, only a few studies have reported postoperative patient-reported outcomes. It has been debated whether player position is related to FAIS. Purpose: To evaluate the change in patient-reported outcome measures (PROMs) in high-level ice hockey players from presurgery to 2 years after arthroscopic treatment for FAIS. The secondary aim was to evaluate differences in outcomes among player positions and whether stick handedness is related to the side of the symptomatic hip. Study Design: Case series; Level of evidence, 4. Methods: Ice hockey players undergoing treatment for FAIS between 2011 and 2019 were prospectively included. Preoperative and 2-year follow-up scores were collected for the following PROMs: HAGOS (Copenhagen Hip and Groin Outcome Score), iHOT-12 (12-item International Hip Outcome Tool), EQ-5D (EuroQol–5 Dimensions) and EQ-VAS (EuroQol–Visual Analog Scale), Hip Sports Activity Scale, and visual analog scale for overall hip function. Player position and stick handedness were collected from public sources. Preoperative and follow-up outcomes were compared for the entire cohort and among player positions. Results: The cohort included 172 ice hockey players with a mean age of 28 years, a mean body mass index of 25.6, and a mean symptom duration of 46.3 months. In the 120 players with 2-year follow-up data, there was significant improvement in all PROMs as compared with presurgery: HAGOS subscales (symptoms, 47.5 vs 68.0; pain, 57.0 vs 75.8; activities of daily living, 62.5 vs 81.0; sports, 40.0 vs 64.7; physical activity, 30.9 vs 57.2; quality of life, 32.5 vs 57.8), iHOT-12 (45.2 vs 66.7), EQ-5D (0.59 vs 0.75), EQ-VAS (68.3 vs 73.2), and visual analog scale for overall hip function (49.6 vs 69.2) (P <.0001 for all). At 2-year follow-up, 83% reported satisfaction with the procedure. There was no difference in the improvement in PROMs among player positions. Further, there was no significant relationship between stick handedness and side of symptomatic hip; however, because of the number of bilateral procedures and large number of left-handed shooters, no conclusions could be drawn. Conclusion: High-level ice hockey players undergoing arthroscopic treatment for FAIS reported improvements in PROMs 2 years after surgery, regardless of player position.
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| 32. |
- Lindman, Ida, et al.
(författare)
-
Loss to follow-up: initial non-responders do not differ from responders in terms of 2-year outcome in a hip arthroscopy registry.
- 2020
-
Ingår i: Journal of hip preservation surgery. - : Oxford University Press (OUP). - 2054-8397. ; 7:2, s. 281-287
-
Tidskriftsartikel (refereegranskat)abstract
- Loss to follow-up in registry studies is a problem due to potential selection bias. There is no consensus on the effect of response rate. The aim of this study was to compare patient-reported outcome measures (PROMs) between responders and initial non-responders (INR) in a hip arthroscopy registry and to examine whether demographics affect the response rate. Data from hip arthroscopies performed at two centres in Gothenburg were collected and the patients were followed up with PROMs. The follow-up was a minimum of 2 years after surgery. All 536 patients who underwent primary hip arthroscopies during 2015 and 2016 and had recorded pre-operative PROMs were included. A total of 396 patients completed the follow-up and were labelled 'Responders' (R) and 107 patients responded after reminders were sent and labelled 'Initial non-responders' (INR). The mean time of follow-up was 24.7±2.9 and 42.5±7.0months for the R- and INR-group, respectively. There were no differences between the two groups at the follow-up for the Copenhagen Hip and Groin Outcome Score, European Quality of life 5 dimensions questionnaire, EQ-VAS, International Hip Outcome Tool or a visual analogue scale for hip function. A larger proportion of R was satisfied after hip arthroscopy compared with INR (86% versus 70%, P=0.0003). INR were younger than responders (31.5±12.5 versus 35.6±12.7years of age). The conclusion of the study was that there were no differences between R and INR at the follow-up across the PROMs except patient satisfaction, where responders were more satisfied.
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| 33. |
- Lindman, Ida, et al.
(författare)
-
Return to Sport for Professional and Subelite Ice Hockey Players After Arthroscopic Surgery for Femoroacetabular Impingement Syndrome
- 2022
-
Ingår i: Orthopaedic Journal of Sports Medicine. - : SAGE Publications. - 2325-9671 .- 2325-9671. ; 10:5
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Femoroacetabular impingement syndrome (FAIS) is a common cause of hip pain, which can prevent ice hockey players from sports participation. Hip arthroscopy is often performed to relieve pain and enable the player to return to sport (RTS) and return to performance (RTP). Purpose: To determine the RTS and RTP rates for ice hockey players at the professional and subelite levels after hip arthroscopy for FAIS. Study Design: Case series; Level of evidence, 4. Methods: High-level ice hockey players who underwent hip arthroscopy for FAIS between 2011 and 2019 were identified using a local hip arthroscopy registry. The player's level was confirmed with ice hockey-specific web pages and was stratified as subelite or professional. Data on the players' careers were extracted from these web pages. Player position was divided into goalkeepers, defensemen, and forwards. Data on participation in games included the season before onset of symptoms, the season before surgery, and the first and second seasons after surgery. RTS was defined as returning to ice hockey after surgery, and RTP was considered as returning to the same league at a comparable level to before symptoms. Results: A total of 80 ice hockey players were included. Comparing presymptom performance with the first season after surgery, the RTS rate was 72%, of which 94% of the players returned to the same or higher level of play. Comparing the presurgery season with the first season after surgery, the RTS rate was 78%. At the second season after surgery, 64% of players still played ice hockey, with a significantly higher return rate among professional players compared with subelite players (96% vs 69%; P = .014). Overall, 85% goalkeepers, 74% forwards, and 60% defensemen returned to sport. Only 28% played at least the same number of games during the first season after surgery as they did during the presymptom season. Conclusion: High-level ice hockey players who underwent hip arthroscopy for FAIS had a high RTS rate, in which the majority returned to the same league. However, only 28% played the same number of games the first season after surgery as they did at the presymptom level. Professional ice hockey players returned more frequently than players on the subelite level.
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| 34. |
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| 35. |
- McLoughlin, D, et al.
(författare)
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Surface complexation of DNA with insoluble monolayers. Influence of divalent counterions
- 2005
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Ingår i: Langmuir. - : American Chemical Society (ACS). - 0743-7463 .- 1520-5827. ; 21:5, s. 1900-1907
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Tidskriftsartikel (refereegranskat)abstract
- DNA interacts with insoluble monolayers made of cationic amphiphiles as well as with monolayers of zwitterionic lipids in the presence of divalent ions. Binding to dioctadecyldimethylammonium bromide (DODAB) or distearoyl-sn-glycero-3-phosphocholine (DSPC) monolayers in the presence of calcium is accompanied by monolayer expansion. For the positively charged DODAB monolayer, this causes a decrease of surface potential, while an increase is observed for the DSPC monolayers. Binding to dipalmitoyl-sn-glycero-3-phosphocholine preserves most of the liquid expanded-liquid condensed coexistence region. The liquid condensed domains adopt an elongated morphology in the presence of DNA, especially in the presence of calcium. The interaction of DNA with phospholipid monolayers is ion specific: the presence of calcium leads to a stronger interaction than magnesium and barium. These results were confirmed by bulk complexation studies.
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| 36. |
- Medronho, B., et al.
(författare)
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Cyclodextrin-grafted cellulose: Physico-chemical characterization
- 2013
-
Ingår i: Carbohydrate Polymers. - : Elsevier BV. - 0144-8617. ; 93:1, s. 324-330
-
Tidskriftsartikel (refereegranskat)abstract
- Cyclodextrins (CDs) can form inclusion complexes with a wide variety of molecules making them very attractive in different areas, such as pharmaceutics, biochemistry, food chemistry and textile. In this communication we will report on the physico-chemical characterization of cellulose modified with CDs by means of infra-red spectroscopy (FTIR), cross polarization magic angle spinning solid state nuclear magnetic resonance (CP-MAS NMR), polarized optical microscopy (POM) and thermal gravimetric analysis (TGA). Both CP-MAS NMR and FTIR indicate that CDs are chemically attached to cellulose backbone through the formation of ester bonds. Furthermore, the CD-grafted cellulose was dissolved in a "superphosphoric" acid solution but, despite the increase of hydrophilicity due to the modification, POM revealed that grafted cellulose was less soluble when compared to the unmodified polymer. The formation of a complex CD-cellulose network is suggested.
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| 37. |
- Moran, M. C., et al.
(författare)
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DNA gel nanoparticles: preparation and controlling the size
- 2009
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Ingår i: Soft Matter. - : Royal Society of Chemistry (RSC). - 1744-6848 .- 1744-683X. ; 5:13, s. 2538-2542
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Tidskriftsartikel (refereegranskat)abstract
- A simple and novel method was used for the preparation of nano-/micro-sized DNA gel particles by nebulisation of a solution of DNA (single-or double-stranded) into an oppositely charged surfactant (cetyltrimethylammonium bromide) or protein (lysozyme, protamine sulfate) solution. The size and size distribution of the particle populations were investigated by means of fluorescence microscopy (FM), photon correlation spectroscopy (PCS) and scanning electron microscopy (SEM). Particles measuring from 0.1 to 10 mu m were obtained. FM studies suggest that the formation of the particles was carried out with conservation of the secondary structure of the nucleic acid molecules. SEM on freeze-dried and Au-shadowed samples showed a distribution of virtually spherical particles. It was found that, in addition to the size of the initial DNA droplets, the cationic agent is a controlling parameter of the particle size.
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| 38. |
- Moran, M. C., et al.
(författare)
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Mixed protein-DNA gel particles for DNA delivery: Role of protein composition and preparation method on biocompatibility
- 2013
-
Ingår i: International Journal of Pharmaceutics. - : Elsevier BV. - 1873-3476 .- 0378-5173. ; 454:1, s. 192-203
-
Tidskriftsartikel (refereegranskat)abstract
- Mixtures of two cationic proteins were used to prepare protein-DNA gel particles, employing associative phase separation and interfacial diffusion (Moran et al., 2009a). By mixing the two proteins, we have obtained particles that displayed higher loading efficiency and loading capacity values than those obtained in single-protein systems. However, nothing is known about the adverse effects on haemocompatibility and cytotoxicity of these protein-DNA gel particles. Here, we examined the interaction of protein-DNA gel particles obtained by two different preparation methods, and their components, with red blood cells and established cells. From a haemolytic point of view, these protein-DNA gel particles were demonstrated to be promising long-term blood-contacting medical devices. Safety evaluation with the established cell lines revealed that, in comparison with proteins in solution, the cytotoxicity was reduced when administered in the protein-DNA systems. In comparison with large-sized particles, the cytotoxic responses of small-sized protein-DNA gel particles showed to be strongly dependent of both the protein composition and the cell line being the tumour cell line HeLa more sensitive to the deleterious effects of the mixed protein-based particles. The observed trends in haemolysis and cell viabilities were in agreement with the degree of complexation values obtained for the protein-DNA gel particles prepared by both preparation methods. (c) 2013 Elsevier B.V. All rights reserved.
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| 39. |
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| 40. |
- Scharf, Lydia, et al.
(författare)
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Inverted CD8 T-Cell Exhaustion and Co-Stimulation Marker Balance Differentiate Aviremic HIV-2-Infected From Seronegative Individuals
- 2021
-
Ingår i: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 12
-
Tidskriftsartikel (refereegranskat)abstract
- HIV-2 is less pathogenic compared to HIV-1. Still, disease progression may develop in aviremic HIV-2 infection, but the driving forces and mechanisms behind such development are unclear. Here, we aimed to reveal the immunophenotypic pattern associated with CD8 T-cell pathology in HIV-2 infection, in relation to viremia and markers of disease progression. The relationships between pathological differences of the CD8 T-cell memory population and viremia were analyzed in blood samples obtained from an occupational cohort in Guinea-Bissau, including HIV-2 viremic and aviremic individuals. For comparison, samples from HIV-1- or dually HIV-1/2-infected and seronegative individuals were obtained from the same cohort. CD8 T-cell exhaustion was evaluated by the combined expression patterns of activation, stimulatory and inhibitory immune checkpoint markers analyzed using multicolor flow cytometry and advanced bioinformatics. Unsupervised multidimensional clustering analysis identified a cluster of late differentiated CD8 T-cells expressing activation (CD38+, HLA-DRint/high), co-stimulatory (CD226+/-), and immune inhibitory (2B4+, PD-1high, TIGIThigh) markers that distinguished aviremic from viremic HIV-2, and treated from untreated HIV-1-infected individuals. This CD8 T-cell population displayed close correlations to CD4%, viremia, and plasma levels of IP-10, sCD14 and beta-2 microglobulin in HIV-2 infection. Detailed analysis revealed that aviremic HIV-2-infected individuals had higher frequencies of exhausted TIGIT+ CD8 T-cell populations lacking CD226, while reduced percentage of stimulation-receptive TIGIT-CD226+ CD8 T-cells, compared to seronegative individuals. Our results suggest that HIV-2 infection, independent of viremia, skews CD8 T-cells towards exhaustion and reduced co-stimulation readiness. Further knowledge on CD8 T-cell phenotypes might provide help in therapy monitoring and identification of immunotherapy targets.
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| 41. |
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| 42. |
- Sharma, Rohini, et al.
(författare)
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Multicenter Reproducibility of F-18-Fluciclatide PET Imaging in Subjects with Solid Tumors
- 2015
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Ingår i: Journal of Nuclear Medicine. - : Society of Nuclear Medicine. - 0161-5505 .- 1535-5667 .- 2159-662X. ; 56:12, s. 1855-1861
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Tidskriftsartikel (refereegranskat)abstract
- Integrins are upregulated on both tumor cells and associated vasculature, where they play an important role in angiogenesis and metastasis. Fluciclatide is an arginine-glycine-aspartic acid peptide with high affinity for alpha(v)beta(3)/alpha(v)beta(5) integrin, which can be radio-labeled for PET imaging of angiogenesis. Thus, F-18-fluciclatide is a potential biomarker of therapeutic response to antiangiogenic inhibitors. The aim of this study was to evaluate the reproducibility of F-18-fluciclatide in multiple solid-tumor types. Methods: Thirty-nine patients underwent PET/CT scanning at 40, 65, and 90 min after injection of F-18-fluciclatide (maximum, 370 MBq) on 2 separate days (2-9 d apart). Patients did not receive any therapy between PET/CT scans. F-18-fluciclatide images were reported and quantitative measures of uptake were extracted using the PERCIST methodology. Intrasubject reproducibility of PET uptake in all measurable lesions was evaluated by calculating relative differences in SUV between PET scans for each lesion during the 2 imaging sessions. Results: Thirty-nine measurable lesions were detected in 26 patients. Lesion uptake correlated strongly across imaging sessions (r = 0.92, P < 0.05, at 40 min; r = 0.94, P < 0.05, at 65 min; r = 0.94, P, 0.05, at 90 min) with a mean relative difference and SD of the relative difference of 0.006 +/- 0.18 at 40 min, 0.003 +/- 0.19 at 65 min, and 0.025 +/- 0.20 at 90 min. This reflects 95% limits of repeatability of 35%-39% for the difference between the 2 SUV measurements or a variability of 18%-20% in agreement from that observed in well-calibrated multicenter F-18-FDG studies. Conclusion: The test-retest reproducibility of F-18-fluciclatide across multiple tumor types has been measured and shown to be acceptable. This is an important step in the development of this in vivo biomarker to identify and quantify response to antiangiogenic therapy in cancer patients.
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| 43. |
- Skogsberg, L., et al.
(författare)
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Improved treatment satisfaction but no difference in metabolic control when using continuous subcutaneous insulin infusion vs. multiple daily injections in children at onset of type 1 diabetes mellitus
- 2008
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Ingår i: Pediatric Diabetes. - : Hindawi Limited. - 1399-5448 .- 1399-543X. ; 9:5, s. 472-9
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The aim of this study was to compare safety, metabolic control, and treatment satisfaction in children/adolescents at onset of type 1 diabetes mellitus who were treated with either continuous subcutaneous insulin infusion (CSII) or multiple daily injections (MDI). RESEARCH DESIGN AND METHODS: Seventy-two children/adolescents (7-17 yr of age) were enrolled in this open, randomized, parallel, multicenter study. Approximately half of the patients were treated with MDI (natural protamine hagedorn [NPH] insulin twice daily and rapid-acting insulin three to -four times daily, n = 38) by pen, and the other half received CSII (n = 34). The patients were followed for 24 months with clinical visits at the entry of the study and after 1, 6, 12, and 24 months. During these visits, hemoglobin A1c, insulin doses, weight, and height were registered. Severe episodes of hypoglycemia and ketoacidosis as well as technical problems were recorded. In addition, the patients/parents answered the Diabetes Treatment Satisfaction Questionnaire. RESULTS: There was no significant difference in metabolic control between the treatment groups. Treatment satisfaction was significantly higher in the group treated with CSII compared with the MDI group (p
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| 44. |
- Snaebjörnsson, Thorkell, 1982, et al.
(författare)
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Most Elite Athletes Who Underwent Hip Arthroscopy for Femoroacetabular Impingement Syndrome Did Not Return to the Same Level of Sport, but the Majority Were Satisfied With the Outcome of Surgery
- 2022
-
Ingår i: Arthroscopy, Sports Medicine, and Rehabilitation. - : Elsevier BV. - 2666-061X. ; 4:3
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose: To evaluate the 2-year outcomes after arthroscopic surgical treatment for femoroacetabular impingement syndrome (FAIS) using validated patient-reported outcome measurements in young elite athletes and to report the rate of return to sport. Methods: Young elite athletes undergoing arthroscopic surgery for FAIS with 2 years of follow-up were included. A young elite athlete was defined as an athlete aged 18 to 22 years at the time of surgery with a Hip Sports Activity Scale (HSAS) level greater than 6 before the onset of symptoms. The following patient-reported outcome measurements were collected prospectively: Copenhagen Hip and Groin Outcome Score, 12-item International Hip Outcome Tool, HSAS, visual analog scale (VAS), European Quality of Life (EQ) 5 Dimensions questionnaire, and EQ VAS. Furthermore, the patients answered a question related to satisfaction with surgery at follow-up. Results: A total of 84 athletes (67 male and 17 female athletes), with a mean age of 19.8 ± 1.5 years, completed the 2-year follow-up. Bilateral hip arthroscopy was performed in 57 athletes, generating a total of 141 included hips. The improvements in the Copenhagen Hip and Groin Outcome Score subscales, 12-item International Hip Outcome Tool, EQ 5 Dimensions questionnaire, EQ VAS, and VAS for overall hip function were statistically significant (P < .001). At the 2-year follow-up, 42% of the athletes reported an HSAS level of either 7 or 8 whereas 28% reported an HSAS level of 5 or 6. In total, 79% of the athletes were satisfied with the surgical procedure. Conclusions: There are significant improvements in outcome measurements at the 2-year follow-up in elite young athletes undergoing arthroscopic hip surgery for FAIS. Although many of the athletes remained in high-level sports 2 years after surgery, only 30% of the athletes returned to sport at the same level. Level of Evidence: Level IV, therapeutic case series. © 2022 The Authors
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| 45. |
- Staaf, Johan, et al.
(författare)
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RNA sequencing-based single sample predictors of molecular subtype and risk of recurrence for clinical assessment of early-stage breast cancer
- 2022
-
Ingår i: npj Breast Cancer. - : Nature Publishing Group. - 2374-4677. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- Multigene assays for molecular subtypes and biomarkers can aid management of early invasive breast cancer. Using RNA-sequencing we aimed to develop single-sample predictor (SSP) models for clinical markers, subtypes, and risk of recurrence (ROR). A cohort of 7743 patients was divided into training and test set. We trained SSPs for subtypes and ROR assigned by nearest-centroid (NC) methods and SSPs for biomarkers from histopathology. Classifications were compared with Prosigna in two external cohorts (ABiM, n = 100 and OSLO2-EMIT0, n = 103). Prognostic value was assessed using distant recurrence-free interval. Agreement between SSP and NC for PAM50 {five subtypes) was high (85%, Kappa = 0.78) for Subtype (four subtypes) very high {90%, Kappa = 0.84) and for ROR risk category high (84%, Kappa = 0.75, weighted Kappa = 0.90). Prognostic value was assessed as equivalent and clinically relevant. Agreement with histopathology was very high or high for receptor status, while moderate for Ki67 status and poor for Nottingham histological grade. SSP and Prosigna concordance was high for subtype (OSLO-EMIT0 83%, Kappa = 0.73 and ABiM 80%, Kappa = 0.72) and moderate and high for ROR risk category (68 and 84%, Kappa = 0.50 and 0.70, weighted Kappa = 0.70 and 0.78). Pooled concordance for emulated treatment recommendation dichotomized for chemotherapy was high (85%, Kappa = 0.66). Retrospective evaluation suggested that SSP application could change chemotherapy recommendations for up to 17% of postmenopausal ER+/HER2-/N0 patients with balanced escalation and de-escalation. Results suggest that NC and SSP models are interchangeable on a group-level and nearly so on a patient level and that SSP models can be derived to closely match clinical tests.
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| 46. |
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| 47. |
- Stål, Per, et al.
(författare)
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Characterisation of human soft palate muscles with respect to fibre types, myosins and capillary supply.
- 2000
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Ingår i: Journal of Anatomy. - 0021-8782 .- 1469-7580. ; 197 ( Pt 2), s. 275-90
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Tidskriftsartikel (refereegranskat)abstract
- Four human soft palate muscles, and palatopharyngeus, the uvula, the levator and tensor veli palatini were examined using enzyme-histochemical, immunohistochemical and biochemical methods and compared with human limb and facial muscles. Our results showed that each palate muscle had a distinct morphological identity and that they generally shared more similarities with facial than limb muscles. The palatopharyngeus and uvula muscles contained 2 of the highest proportions of type II fibres ever reported for human muscles. In contrast, the levator and tensor veli palatini muscles contained predominantly type I fibres. A fetal myosin heavy chain isoform (MyHC), not usually found in normal adult limb muscles, was present in a small number of fibres in all palate muscles. The mean muscle fibre diameter was smaller than in limb muscles and the individual and intramuscular variability in diameter and shape was considerable. All palate muscles had a high capillary density and an unusually high mitochondrial enzyme activity in the type II fibres, in comparison with limb muscles. No ordinary muscle spindles were observed. The fibre type and MyHC composition indicate that the palatopharyngeus and uvula muscles are functionally involved in quick movements whereas the levator and tensor veli palatini muscles perform slower and more continuous contractions. The high aerobic capacity and the rich capillarisation suggest that the palate muscles are relatively fatigue resistant. Absence of ordinary muscle spindles indicates a special proprioceptive control system. The special morphology of the palate muscles may be partly related to the unique anatomy with only one skeletal insertion, a feature consistent with muscle work at low load and tension and which may influence the cytoarchitecture of these muscles. Other important factors determining the special morphological characteristics might be specific functional requirements, distinct embryological origin and phylogenetic factors.
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| 49. |
- Valachis, A., 1984-, et al.
(författare)
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Palbociclib dose patterns in Swedish patients with metastatic breast cancer : 5-year update from the SIRI study
- 2023
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Ingår i: Annals of Oncology. - : Elsevier. - 0923-7534 .- 1569-8041. ; 34:Suppl. 2, s. S362-S362
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Although palbociclib combined with endocrine therapy is a well-established treatment option in patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC), there is limited evidence on patterns of dose reductions in real-world setting. The Swedish Ibrance Registries Insights (SIRI) study investigated real-world dose patterns using a nationwide cohort of palbociclib-treated MBC patients...Methods: This was a retrospective study utilizing population-based Swedish Health Data Registers. The cohort included all patients ≥ 18 years with ≥ 1 dispensation of palbociclib from January 2017 – June 2022. Minimum follow-up was 3 months. Starting dose and dose changes for the full population and for different age groups, in total and over time, was investigated...Results: 2058 patients were identified and the median (IQR) age at treatment initiation was 68.4 (15.7) years. Patients were stratified into three age groups: <50, 50-69, ≥70 years, with the following distribution: 9.9%, 46.1%, and 44.0%, respectively. Most patients were initiated on 125 mg (82.0%), with a lower share for older patients (≥70 years; 74.4%). In total, 45.5% of patients had ≥ 1 dose reduction, with a higher frequency for older patients (≥70 years; 48.5%). Median (IQR) time to first dose...Conclusions: Most Swedish palbociclib-treated patients were initiated on the recommended dose, but a lower starting dose and a higher frequency of dose reductions were observed for older patients. The time to dose reduction was equal across age groups, whereas the probability for dose reduction increased over time for older patients, and for patients with a start dose of 100 mg...
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| 50. |
- Öhlin, Axel, 1990, et al.
(författare)
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Good 5-year outcomes after arthroscopic treatment for femoroacetabular impingement syndrome
- 2020
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Ingår i: Knee Surgery, Sports Traumatology, Arthroscopy. - : Springer Science and Business Media LLC. - 0942-2056 .- 1433-7347. ; 28, s. 1311-1316
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Tidskriftsartikel (refereegranskat)abstract
- © 2019, The Author(s). Purpose: The purpose of the present study was to evaluate the outcome of arthroscopic treatment for femoroacetabular impingement (FAI) syndrome 5 years post-surgery using patient-reported outcome scores (PROMs) validated for a young and active population with hip complaints. Methods: Patients were prospectively included in the study. A total of 184 patients [males = 110 (59.8%), females = 74 (40.2%)], with mean age 38.0, underwent arthroscopic treatment for FAI syndrome and were analysed. Preoperatively and at the 5-year follow-up, patients completed a set of self-administered web-based PROMs consisting of the International Hip Outcome Tool (iHOT-12), the Copenhagen Hip and Groin Outcome Score (HAGOS), the Hip Sports Activity Scale (HSAS), the EuroQoL-5 Dimension Questionnaire (EQ-5D), the EQ-Visual Analogue Scale (VAS) and the VAS for overall hip function and overall satisfaction. The Wilcoxon signed rank test was used to compare preoperative PROM values with those obtained at the 5-year follow-up. Results: A comparison of preoperative PROM scores and those obtained at the 5-year follow-up revealed statistically significant improvements for all outcome scores (p < 0.05), except for the HSAS score, which were unchanged; iHOT-12 (42.9 vs 67.2), HAGOS different subscales (50.2 vs 69.6, 55.7 vs 76.1, 59.2 vs 72.3, 41.1 vs 66.4, 30.8 vs 60.2, 31.6 vs 60.4), EQ-5D (0.570 vs 0.742), EQ-VAS (66.6 vs 74.4), HSAS (3.13 vs 3.17) and VAS for overall hip function (47.9 vs 69.2). At the 5-year follow-up, 154 patients reported that they were satisfied with surgery (84.6%). Survivorship at the 5-year follow-up was 86.4%. Conclusion: Arthroscopic treatment for FAI syndrome yields good patient-reported outcome at the 5-year follow-up. Level of evidence: II.
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