| 1. |
- Ayeni, O. R., et al.
(författare)
-
Clinical and Radiographic Criteria Define "Acceptable" Surgical Correction of Hip Femoroacetabular Impingement Syndrome as Well as Postoperative Complications: An International Modified Delphi Study
- 2023
-
Ingår i: Arthroscopy-the Journal of Arthroscopic and Related Surgery. - : Elsevier BV. - 0749-8063. ; 39:5, s. 1198-1210
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives: To develop recommendations for clinical and radiographic criteria to help define the "acceptable" surgical correction of femoroacetabular impingement syndrome (FAIS) and identify/define complications postoperatively. Methods: A 3-phase modified Delphi study was conducted involving a case-based survey; a Likert/multiple choice-based survey concerning radiographic and physical examination characteristics to help define FAIS correction, as well as the prevalence and definition of potential postoperative complications; and 2 consensus meetings. Results: Of the 75 experts invited, 54 completed the Phase I survey, 50 completed the Phase II survey (72% and 67% response rate), and 50 participated in the Phase III consensus meetings. For both typical and atypical (complex) cases, there was consensus that fluoroscopy with multiple views and dynamic hip assessment should be used intraoperatively (96% and 100%, respectively). For typical FAIS cases, the Expert Panel agreed that Dunn lateral and anteroposterior radiographs were the most important radiographs to evaluate the hip postoperatively (88%, consensus). When asked about evaluating the correction of cam impingement postoperatively, 87% voted that they use subjective evaluation of the "sphericity" of the femoral head. In the case of focal and global pincer-type FAIS, there was consensus that the reduction or elimination of the crossover sign (84%) and lateral center-edge angle (91%) were important to inform the extent of the FAIS correction. There was consensus for recommending further investigation at 6 months postoperatively if hip pain had increased/plateaued (92% agreed); that additional investigation and treatment should occur between 6 and 12 months (90% agreed); and that a reoperation may be recommended at 12 months or later following this investigation period (89% agreed). Conclusions: This consensus project identified the importance of using fluoroscopy and dynamic hip assessment intraoperatively; Dunn lateral and anteroposterior view radiographs postoperatively; evaluating the "sphericity" of the femoral head for cam-type correction and the use of dynamic hip assessment; reducing/eliminating the crossover sign for focal pincertype FAIS; evaluating the lateral center-edge angle for global pincer-type FAIS; and avoiding overcorrection of pincer-type FAIS. In cases in which postoperative hip pain increased/plateaued, further investigation and treatment is warranted between 6 and 12 months, and a reoperation may be recommended at a minimum of 12 months depending on the cause of the hip pain. Clinical Relevance: Hip arthroscopy surgeons have yet to reach a firm agreement on what constitutes an "acceptable" or "good" surgery radiographically and how they can achieve desired clinical outcomes. Although this was a comprehensive effort, more study is needed to determine therapeutic thresholds that can be universally applied.
|
|
| 2. |
- Almquist, Joachim, 1980, et al.
(författare)
-
Unraveling the Pharmacokinetic Interaction of Ticagrelor and MEDI2452 (Ticagrelor Antidote) by Mathematical Modeling
- 2016
-
Ingår i: CPT: Pharmacometrics and Systems Pharmacology. - : Wiley. - 2163-8306. ; 5:6, s. 313-323
-
Tidskriftsartikel (refereegranskat)abstract
- The investigational ticagrelor-neutralizing antibody fragment, MEDI2452, is developed to rapidly and specifically reverse the antiplatelet effects of ticagrelor. However, the dynamic interaction of ticagrelor, the ticagrelor active metabolite (TAM), and MEDI2452, makes pharmacokinetic (PK) analysis nontrivial and mathematical modeling becomes essential to unravel the complex behavior of this system. We propose a mechanistic PK model, including a special observation model for post-sampling equilibration, which is validated and refined using mouse in vivo data from four studies of combined ticagrelor-MEDI2452 treatment. Model predictions of free ticagrelor and TAM plasma concentrations are subsequently used to drive a pharmacodynamic (PD) model that successfully describes platelet aggregation data. Furthermore, the model indicates that MEDI2452-bound ticagrelor is primarily eliminated together with MEDI2452 in the kidneys, and not recycled to the plasma, thereby providing a possible scenario for the extrapolation to humans. We anticipate the modeling work to improve PK and PD understanding, experimental design, and translational confidence.
|
|
| 3. |
- Pehrsson, S., et al.
(författare)
-
Hemostatic effects of the ticagrelor antidote MEDI2452 in pigs treated with ticagrelor on a background of aspirin
- 2017
-
Ingår i: Journal of Thrombosis and Haemostasis. - : Elsevier BV. - 1538-7836 .- 1538-7933. ; 15:6, s. 1213-1222
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Ticagrelor, a P2Y12 antagonist, is approved for the prevention of thromboembolic events. However, antiplatelet therapies carry a risk of bleeding. Objective: To explore the hemostatic effects of MEDI2452, an antidote for ticagrelor. Methods: Pigs, pretreated with aspirin, were given an intravenous infusion of ticagrelor or vehicle. At the end of the infusion, a piece of a liver lobe was cut off and a bolus of MEDI2452 or vehicle was administered intravenously. Blood was collected to monitor blood loss, mean arterial blood pressure (MAP) was recorded and survival time was observed over 4 h. Blood samples for drug plasma exposures and platelet aggregation were collected. Results: MEDI2452 eliminated the free concentrations of ticagrelor and its active metabolite AR-C124910XX within 5 min. ADP-induced platelet aggregation was close to normal at 60 min, which was not significantly different from aspirin alone. MEDI2452 numerically reduced ticagrelor-mediated effects: bodyweight- adjusted blood loss in the 15-to 90-min interval, 12 (confidence interval [ CI] 95% 7-28] vs. 17 (CI 95% 5-31) (ticagrelor and aspirin) vs. 5 (CI 95% 3-9) mL kg(-1) (aspirin alone), survival 70% (CI 95% 47-100) vs. 45% (CI 95% 21-92) (ticagrelor and aspirin) vs. 100% (CI 95% 100-100) (aspirin alone), and median survival time, 240 (CI 95% 180-240) vs. 169 (CI 95% 64-240) (ticagrelor and aspirin) vs. 240 (CI 95% 240-240) min (aspirin alone). Finally, MEDI2452 significantly attenuated the decline in MAP, 0.08 (CI 95% 0.07-0.09) vs. 0.141 (CI 95% 0.1350.148) (ticagrelor and aspirin) vs. 0.04 (CI 95% 0.030.05) mmHg per min (aspirin alone) and maintained MAP at a significantly higher level, 73 (CI 95% 51-95) vs. 48 (CI 95% 25-70) (ticagrelor and aspirin) vs. 115 (CI 95% 94136) mmHg (aspirin alone). Conclusion: MEDI2452 eliminated free ticagrelor and AR-C124910XX within 5 min. This translated into a gradual normalization of ADPinduced platelet aggregation and significant improvement in blood pressure and numerical but non-significant improvements in blood-loss and survival.
|
|
| 4. |
- Dabkowska, A. P., et al.
(författare)
-
Temperature responsive lipid liquid crystal layers with embedded nanogels
- 2017
-
Ingår i: Chemical Communications. - : Royal Society of Chemistry. - 1359-7345 .- 1364-548X. ; 53:8, s. 1417-1420
-
Tidskriftsartikel (refereegranskat)abstract
- Polymer nanogels are embedded within layers consisting of a nonlamellar liquid crystalline lipid phase to act as thermoresponsive controllers of layer compactness and hydration. As the nanogels change from the swollen to the collapsed state via a temperature trigger, they enable on-demand release of water from the mixed polymer-lipid layer while the lipid matrix remains intact. Combining stimuli-responsive polymers with responsive lipid-based mesophase systems opens up new routes in biomedical applications such as functional biomaterials, bioanalysis and drug delivery.
|
|
| 5. |
- Kragelund, C, et al.
(författare)
-
Scandinavian fellowship for oral pathology and oral medicine : statement on oral pathology and oral medicine in the European dental curriculum
- 2010
-
Ingår i: Journal of Oral Pathology & Medicine. - : Wiley. - 0904-2512 .- 1600-0714. ; 39:10, s. 800-801
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: For many years, dentists have migrated between the Scandinavian countries without an intentionally harmonized dental education. The free movement of the workforce in the European Union has clarified that a certain degree of standardization or harmonization of the European higher education acts, including the dental education, is required. As a result of the Bologna process, the Association for Dental Education in Europe and the thematic network DentEd have generated guidelines in the document 'Profile and Competences for the European Dentist' (PCD). This document is meant to act as the leading source in revisions of dental curricula throughout Europe converging towards a European Dental Curriculum. In order to render the best conditions for future curriculum revisions providing the best quality dentist we feel obliged to analyse and comment the outlines of oral pathology and oral medicine in the PCD.METHODS: The representatives agreed upon definitions of oral pathology and oral medicine, and competences in oral pathology and oral medicine that a contemporary European dentist should master. The competences directly related to oral pathology and oral medicine were identified, within the PCD.RESULTS: The subject representatives suggested eighteen additions and two rewordings of the PCD, which all were substantiated by thorough argumentation.PERSPECTIVES: Hopefully, this contribution will find support in future revisions of the PCD in order to secure the best quality dental education.
|
|
| 6. |
- Lenton, S, et al.
(författare)
-
Dynamic footprint of sequestration in the molecular fluctuations of osteopontin.
- 2015
-
Ingår i: Journal of the Royal Society Interface. - : The Royal Society. - 1742-5662 .- 1742-5689. ; 12:110
-
Tidskriftsartikel (refereegranskat)abstract
- The sequestration of calcium phosphate by unfolded proteins is fundamental to the stabilization of biofluids supersaturated with respect to hydroxyapatite, such as milk, blood or urine. The unfolded state of osteopontin (OPN) is thought to be a prerequisite for this activity, which leads to the formation of core-shell calcium phosphate nanoclusters. We report on the structures and dynamics of a native OPN peptide from bovine milk, studied by neutron spectroscopy and small-angle X-ray and neutron scattering. The effects of sequestration are quantified on the nanosecond- ångström resolution by elastic incoherent neutron scattering. The molecular fluctuations of the free phosphopeptide are in agreement with a highly flexible protein. An increased resilience to diffusive motions of OPN is corroborated by molecular fluctuations similar to those observed for globular proteins, yet retaining conformational flexibilities. The results bring insight into the modulation of the activity of OPN and phosphopeptides with a role in the control of biomineralization. The quantification of such effects provides an important handle for the future design of new peptides based on the dynamics-activity relationship.
|
|
| 7. |
- Mahajan, Anubha, et al.
(författare)
-
Fine-mapping type 2 diabetes loci to single-variant resolution using high-density imputation and islet-specific epigenome maps
- 2018
-
Ingår i: Nature Genetics. - : NATURE PUBLISHING GROUP. - 1061-4036 .- 1546-1718. ; 50:11, s. 1505-
-
Tidskriftsartikel (refereegranskat)abstract
- We expanded GWAS discovery for type 2 diabetes (T2D) by combining data from 898,130 European-descent individuals (9% cases), after imputation to high-density reference panels. With these data, we (i) extend the inventory of T2D-risk variants (243 loci,135 newly implicated in T2D predisposition, comprising 403 distinct association signals); (ii) enrich discovery of lower-frequency risk alleles (80 index variants with minor allele frequency <5%,14 with estimated allelic odds ratio >2); (iii) substantially improve fine-mapping of causal variants (at 51 signals, one variant accounted for >80% posterior probability of association (PPA)); (iv) extend fine-mapping through integration of tissue-specific epigenomic information (islet regulatory annotations extend the number of variants with PPA >80% to 73); (v) highlight validated therapeutic targets (18 genes with associations attributable to coding variants); and (vi) demonstrate enhanced potential for clinical translation (genome-wide chip heritability explains 18% of T2D risk; individuals in the extremes of a T2D polygenic risk score differ more than ninefold in prevalence).
|
|
| 8. |
|
|
| 9. |
- Nylander, S., et al.
(författare)
-
A complementing approach for identifying ethical issues in care robotics - Grounding ethics in practical use
- 2012
-
Ingår i: RO-MAN, 2012 IEEE. - : IEEE. - 9781467346054 ; , s. 797-802, s. 797-802
-
Konferensbidrag (refereegranskat)abstract
- We use a long-term study of a robotic eating-aid for disabled users to illustrate how empirical use give rise to a set of ethical issues that might be overlooked in ethic discussions based on theoretical extrapolation of the current state-of-the-art in robotics. This approach provides an important complement to the existing robot ethics by revealing new issues as well as providing actionable guidance for current and future robot design. We discuss our material in relation to the literature on robot ethics, specifically the risk of robots performing care taking tasks and thus causing increased isolation for care recipients. Our data identifies a different set of ethical issues such as independence, privacy, and identity where robotics, if carefully designed and developed, can make positive contributions.
|
|
| 10. |
- Poletto, F. S., et al.
(författare)
-
Tailoring the internal structure of liquid crystalline nanoparticles responsive to fungal lipases : A potential platform for sustained drug release
- 2016
-
Ingår i: Colloids and Surfaces B: Biointerfaces. - : Elsevier BV. - 0927-7765. ; 147, s. 210-216
-
Tidskriftsartikel (refereegranskat)abstract
- Lipases are key components in the mechanisms underlying the persistence and virulence of infections by fungi, and thus also promising triggers for bioresponsive lipid-based liquid crystalline nanoparticles. We here propose a platform in which only a minor component of the formulation is susceptible to cleavage by lipase and where hydrolysis triggers a controlled phase transition within the nanoparticles that can potentially allow for an extended drug release. The responsive formulations were composed of phytantriol, which was included as a non-cleavable major component and polysorbate 80, which serves both as nanoparticle stabilizer and potential lipase target. To monitor the structural changes resulting from lipase activity with sufficient time resolution, we used synchrotron small angle x-ray scattering. Comparing the effect of the two different lipases used in this work, lipase B from Candida Antarctica, (CALB) and lipase from Rhizomucor miehei (RMML), only CALB induced phase transition from bicontinuous reverse cubic to reverse hexagonal phase within the particles. This phase transition can be attributed to an increasing amount of oleic acid formed on cleavage of the polysorbate 80. However, when also a small amount of a cationic surfactant was included in the formulation, RMML could trigger the corresponding phase transition as well. The difference in activity between the two lipases can tentatively be explained by a difference in their interaction with the nanoparticle surface. Thus, a bioresponsive system for treating fungal infections, with a tunable selectivity for different types of lipases, could be obtained by tuning the composition of the nanoparticle formulation.
|
|
| 11. |
- Tournillon, A-S, et al.
(författare)
-
p53 binds the mdmx mRNA and controls its translation
- 2017
-
Ingår i: Oncogene. - : NATURE PUBLISHING GROUP. - 0950-9232 .- 1476-5594. ; 36:5, s. 723-730
-
Tidskriftsartikel (refereegranskat)abstract
- MDMX and MDM2 are two nonredundant essential regulators of p53 tumor suppressor activity. MDM2 controls p53 expression levels, whereas MDMX is predominantly a negative regulator of p53 trans-activity. The feedback loops between MDM2 and p53 are well studied and involve both negative and positive regulation on transcriptional, translational and post-translational levels but little is known on the regulatory pathways between p53 and MDMX. Here we show that overexpression of p53 suppresses mdmx mRNA translation in vitro and in cell-based assays. The core domain of p53 binds the 5' untranslated region (UTR) of the mdmx mRNA in a zinc-dependent manner that together with a trans-suppression domain located in p53 N-terminus controls MDMX synthesis. This interaction can be visualized in the nuclear and cytoplasmic compartment. Fusion of the mdmx 5' UTR to the ovalbumin open reading frame leads to suppression of ovalbumin synthesis. Interestingly, the transcription inactive p53 mutant R273H has a different RNA-binding profile compared with the wild-type p53 and differentiates the synthesis of MDMX isoforms. This study describes p53 as a trans-suppressor of the mdmx mRNA and adds a further level to the intricate feedback system that exist between p53 and its key regulatory factors and emphasizes the important role of mRNA translation control in regulating protein expression in the p53 pathway.
|
|
| 12. |
|
|
| 13. |
- Wood, Christian M., et al.
(författare)
-
Prevalence and influence of cys407* Grm2 mutation in Hannover-derived Wistar rats : mGlu2 receptor loss links to alcohol intake, risk taking and emotional behaviour.
- 2017
-
Ingår i: Neuropharmacology. - : Elsevier BV. - 0028-3908 .- 1873-7064. ; 115, s. 128-138
-
Forskningsöversikt (refereegranskat)abstract
- Modulation of metabotropic glutamate 2 (mGlu2) receptor function has huge potential for treating psychiatric and neurological diseases. Development of drugs acting on mGlu2 receptors depends on the development and use of translatable animal models of disease. We report here a stop codon mutation at cysteine 407 in Grm2 (cys407*) that is common in some Wistar rats. Therefore, researchers in this field need to be aware of strains with this mutation. Our genotypic survey found widespread prevalence of the mutation in commercial Wistar strains, particularly those known as Han Wistar. Such Han Wistar rats are ideal for research into the separate roles of mGlu2 and mGlu3 receptors in CNS function. Previous investigations, unknowingly using such mGlu2 receptor-lacking rats, provide insights into the role of mGlu2 receptors in behaviour. The Grm2 mutant rats, which dominate some selectively bred lines, display characteristics of altered emotionality, impulsivity and risk-related behaviours and increased voluntary alcohol intake compared with their mGlu2 receptor-competent counterparts. In addition, the data further emphasize the potential therapeutic role of mGlu2 receptors in psychiatric and neurological disease, and indicate novel methods of studying the role of mGlu2 and mGlu3 receptors.
|
|
| 14. |
- Örnebro, Jörgen, et al.
(författare)
-
The behaviour of the high molecular-weight glutenin subunit 1Dx5, the 58 kDa central repetitive domain and a-gliadins at the air-aqueous interface.
- 2003
-
Ingår i: Journal of Cereal Science. - 0733-5210. ; 38:2, s. 147-156
-
Tidskriftsartikel (refereegranskat)abstract
- The surface pressure–molecular area (–A) relationship for spread layers of the high molecular-weight glutenin subunit 1Dx5, a 58 kDa peptide derived from the central repetitive domain of the subunit, and an -gliadin fraction was measured by means of a surface film balance (Langmuir trough). The aqueous phase was a 10 mM acetate buffer, pH 4.0, either with or without 100 mM NaCl. Subunit 1Dx5 generated much higher surface pressures than the 58 kDa peptide, whereas the -gliadin fraction generally gave higher surface pressures than subunit 1Dx5. Furthermore, subunit 1Dx5, but not the 58 kDa peptide or the -gliadin fraction, formed a highly cohesive film. The differences in the interfacial behaviour of subunit 1Dx5 and the 58 kDa peptide were ascribed to significant hydrophobic interactions for the subunit. The reversibility of a compression–expansion cycle was generally greater for the second cycle than for the first. For subunit 1Dx5 and the -gliadins, but not the 58 kDa peptide, the reversibility was increased when NaCl was present in the aqueous phase.
|
|
| 15. |
- Ainalem, Marie-Louise, et al.
(författare)
-
On the Ability of PAMAM Dendrimers and Dendrimer/DNA Aggregates To Penetrate POPC Model Biomembranes
- 2010
-
Ingår i: Journal of Physical Chemistry B. - : American Chemical Society (ACS). - 1520-6106 .- 1520-5207. ; 114:21, s. 7229-7244
-
Tidskriftsartikel (refereegranskat)abstract
- Poly(amido amine) (PAMAM) dendrimers have previously been shown, as cationic condensing agents of DNA, to have high potential for nonviral gene delivery. This study addresses two key issues for gene delivery: the interaction of the biomembrane with (i) the condensing agent (the cationic PAMAM dendrimer) and (ii) the corresponding dendrimer/DNA aggregate. Using in situ null ellipsometry and neutron reflection, parallel experiments were carried out involving dendrimers or generations 2 (G2), 4 (G4), and 6 (G6). The study demonstrates that free dendrimers of all three generations were able to traverse supported palmitoyloleoylphosphatidylcholine (POPC) bilayers deposited on silica surfaces. The model biomembranes were elevated front the solid surfaces upon dendrimer penetration, which offers a promising new way to generate more realistic model biomembranes where the contact with the supporting surface is reduced and where aqueous cavities are present beneath the bilayer. The largest dendrimer (GO) induced partial bilayer destruction directly upon penetration, whereas the smaller dendrimers (G2 and G4) leave the bilayer intact, so we propose that lower generation dendrimers have greater potential as transfection mediators. In addition to the experimental observations, coarse-grained simulations on the interaction between generation 3 (03) dendrimers and POPC bilayers were performed in the absence and presence of a bilayer-supporting negatively charged surface that emulates the support. The simulations demonstrate that G3 is transported across free-standing POPC bilayers by direct penetration and not by endocytosis. The penetrability was, however, reduced in the presence of a surface, indicating that the membrane transport observed experimentally was not driven solely by the surface. The experimental reflection techniques were also applied to dendrimer/DNA aggregates of charge ratio = 0.5, and while G2/DNA and G4/DNA aggregates interact with POPC bilayers. G6/DNA displays no such interaction. These results indicate that, in contrast to free dendrimer molecules, dendrimer/DNA aggregates of low charge ratios are not able to traverse a membrane by direct penetration.
|
|
| 16. |
- Alonso, Lorena, et al.
(författare)
-
TIGER : The gene expression regulatory variation landscape of human pancreatic islets
- 2021
-
Ingår i: Cell Reports. - : Elsevier BV. - 2211-1247. ; 37:2
-
Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWASs) identified hundreds of signals associated with type 2 diabetes (T2D). To gain insight into their underlying molecular mechanisms, we have created the translational human pancreatic islet genotype tissue-expression resource (TIGER), aggregating >500 human islet genomic datasets from five cohorts in the Horizon 2020 consortium T2DSystems. We impute genotypes using four reference panels and meta-analyze cohorts to improve the coverage of expression quantitative trait loci (eQTL) and develop a method to combine allele-specific expression across samples (cASE). We identify >1 million islet eQTLs, 53 of which colocalize with T2D signals. Among them, a low-frequency allele that reduces T2D risk by half increases CCND2 expression. We identify eight cASE colocalizations, among which we found a T2D-associated SLC30A8 variant. We make all data available through the TIGER portal (http://tiger.bsc.es), which represents a comprehensive human islet genomic data resource to elucidate how genetic variation affects islet function and translates into therapeutic insight and precision medicine for T2D.
|
|
| 17. |
|
|
| 18. |
|
|
| 19. |
|
|
| 20. |
- Bain, C. D., et al.
(författare)
-
Complexes of surfactants with oppositely charged polymers at surfaces and in bulk
- 2010
-
Ingår i: Advances in Colloid and Interface Science. - : Elsevier BV. - 0001-8686 .- 1873-3727. ; 155:1-2, s. 32-49
-
Tidskriftsartikel (refereegranskat)abstract
- Addition of surfactants to aqueous solutions of polyelectrolytes carrying an opposite charge causes the spontaneous formation of complexes in the bulk phase in certain concentration ranges. Under some conditions, compact monodisperse multichain complexes are obtained in the bulk. The size of these complexes depends on the mixing procedure and it can be varied in a controlled way from nanometers up to micrometers. The complexes exhibit microstructures analoguous to those of the precipitates formed at higher concentrations. In other cases, however, the bulk complexes are large, soft and polydisperse. In most cases, the dispersions are only kinetically stable and exhibit pronounced non-equilibrium features. Association at air-water interfaces readily occurs, even at very small concentrations. When the surfactant concentration is small, the surface complexes are usually made of a surfactant monolayer to which the polymer binds and adsorbs in a flat-like configuration. However, under some conditions, thicker layers can be found, with bulk complexes sticking to the surface. The association at solid-water interfaces is more complex and depends on the specific interactions between surfactants, polymers and the surface. However, the behaviour can be understood if distinctions between hydrophilic surfaces and hydrophobic surfaces are made. Note that the behaviour at air-water interfaces is closer to that of hydrophobic than that of hydrophilic solid surfaces. The relation between bulk and surface complexation will be discussed in this review. The emphasis will be given to the results obtained by the teams of the EC-funded Marie Curie RTN "SOCON".
|
|
| 21. |
|
|
| 22. |
|
|
| 23. |
|
|
| 24. |
|
|
| 25. |
- Black, Camilla F, et al.
(författare)
-
Linear dsDNA Partitions Spontaneously into the Inverse Hexagonal Lyotropic Liquid Crystalline Phases of Phospholipids.
- 2010
-
Ingår i: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 1520-5126 .- 0002-7863. ; 132:28, s. 9728-9732
-
Tidskriftsartikel (refereegranskat)abstract
- Recently, we reported that DNA associated with inverse hexagonal (H(II)) lyotropic liquid crystal phases of the lipid 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) was actively transcribed by T7 RNA polymerase. (1) Our findings suggested that key components of the transcription process, probably the T7 RNA polymerase and the DNA, remained associated with the monolithic H(II) phase throughout transcription. Here, we investigate the partitioning of DNA between an H(II) lyotropic liquid crystal phase and an isotropic supernatant phase in order to develop insights into the localization of DNA in liquid crystalline environments. Our results show that linear double stranded DNA (dsDNA) molecules partition spontaneously into monolithic preformed H(II) liquid crystal phases of DOPE. We propose that this process is driven by the increase in entropy due to the release of counterions from the DNA when it inserts into the aqueous pores of the H(II) phase.
|
|
| 26. |
|
|
| 27. |
- Burrell, Jamie, et al.
(författare)
-
Using Curvature Power to Map the Domain of Inverse Micellar Cubic Phases : The Case of Aliphatic Aldehydes in 1,2-Dioleoyl-sn-glycero-3-phosphoethanolamine
- 2017
-
Ingår i: Langmuir. - : American Chemical Society (ACS). - 0743-7463 .- 1520-5827. ; 33:44, s. 12804-12813
-
Tidskriftsartikel (refereegranskat)abstract
- Oxylipins, or fatty aldehydes, are a class of molecules produced from membrane lipids as a result of oxidative stress or enzyme-mediated peroxidation. Here we report the effects of two biologically important fatty aldehydes, trans,trans-2,4-decanedienal (DD) and cis-11-hexadecenal (HD), on the phase behavior of the lipid 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) in water. We compare the phase behavior of DD/DOPE and HD/DOPE mixtures to the phase behavior of oleic acid/DOPE mixtures and show that DD, HD, and oleic acid have similar effects on the phase diagrams of DOPE. Notably, both DD and HD, like oleic acid, induce the formation of Fd3m inverse micellar cubic phases in DOPE/water mixtures. This is the first time that Fd3m phases in fatty aldehyde-containing mixtures have been reported. We assess the effects of DD, HD, and oleic acid on DOPE in terms of lipid spontaneous curvatures and propose a method to predict the formation of Fd3m phases from the curvature power of amphiphiles. This methodology predicts that Fd3m phases will become stable if the spontaneous curvature of a lipid mixture is -0.48 ± 0.05 nm-1 or less.
|
|
| 28. |
- Caboi, F, et al.
(författare)
-
Lipase action on a monoolein/sodium oleate aqueous cubic liquid crystalline phase - a NMR and X-ray diffraction study
- 2002
-
Ingår i: Colloids and Surfaces B: Biointerfaces. - 1873-4367. ; 26:1-2, s. 159-171
-
Tidskriftsartikel (refereegranskat)abstract
- The effect of adding Thermomyces (formerly Humicola) lanuginosa lipase (TLL) to a monoolein (MO)/sodium oleate (NaO) aqueous cubic liquid crystalline phase has been studied. H-1-NMR, C-13-NMR, H-1-PGSE (Pulsed-magnetic field Gradient Spin-Echo) self-diffusion measurements, and Small Angle X-ray Diffraction were used to follow the degradation of the cubic phase. The reaction sequence in terms of phase transitions follows the order bicontinuous cubic --> reverse hexagonal --> micellar cubic --> micellar phase and corresponds to the previously determined phase diagrams. These changes correlate with changes in the lipid composition observed by C-13-NMR and confirmed by HPLC analysis. The initial decrease of the diffusion coefficients of water and lipid can be related to the transformation of the bicontinuous cubic phase to a reverse hexagonal structure. (C) 2002 Elsevier Science B.V. All rights reserved.
|
|
| 29. |
- Cedernaes, Jonathan, et al.
(författare)
-
Comprehensive analysis of localization of 78 solute carrier genes throughout the subsections of the rat gastrointestinal tract
- 2011
-
Ingår i: Biochemical and Biophysical Research Communications - BBRC. - : Elsevier BV. - 0006-291X .- 1090-2104. ; 411:4, s. 702-707
-
Tidskriftsartikel (refereegranskat)abstract
- Solute carriers (SLCs), the second largest super-family of membrane proteins in the human genome, transport amino acids, sugars, fatty acids, inorganic ions, essential metals and drugs over membranes. To date no study has provided a comprehensive analysis of SLC localization along the entire GI tract. The aim of the present study was to provide a comprehensive, segment-specific description of the localization of SLC genes along the rat Cl tract by employing bioinformatics and molecular biology methods. The Unigene database was screened for rat SLC entries in the intestinal tissue. Using qPCR we measured expression of the annotated genes in the Cl tract divided into the following segments: the esophagus, the corpus and the antrum of the stomach, the proximal and distal parts of the duodenum, ileum, jejunum and colon, and the cecum. Our Unigene-derived gene pool was expanded with data from in-house tissue panels and a literature search. We found 44 out of 78 (56%) of gut SLC transcripts to be expressed in all Cl tract segments, whereas the majority of remaining SLCs were detected in more than five segments. SLCs are predominantly expressed in gut regions with absorptive functions although expression was also found in segments unrelated to absorption. The proximal jejunum had the highest number of differentially expressed SLCs. In conclusion, SLCs are a crucial molecular component of the Cl tract, with many of them expressed along the entire GI tract. This work presents the first overall road map of localization of transporter genes in the Cl tract.
|
|
| 30. |
- Clauzel, Maryline, et al.
(författare)
-
Surface Deposition and Phase Behavior of Oppositely Charged Polyion-Surfactant Ion Complexes. Delivery of Silicone Oil Emulsions to Hydrophobic and Hydrophilic Surfaces.
- 2011
-
Ingår i: ACS Applied Materials and Interfaces. - : American Chemical Society (ACS). - 1944-8244 .- 1944-8252. ; 3, s. 2451-2462
-
Tidskriftsartikel (refereegranskat)abstract
- The adsorption from mixed polyelectrolyte-surfactant solutions at hydrophobized silica surfaces was investigated by in situ null-ellipsometry, and compared to similar measurements for hydrophilic silica surfaces. Three synthetic cationic copolymers of varying hydrophobicity and one cationic hydroxyethyl cellulose were compared in mixtures with the anionic surfactant sodium dodecylsulfate (SDS) in the absence or presence of a dilute silicone oil emulsion. The adsorption behavior was mapped while stepwise increasing the concentration of SDS to a polyelectrolyte solution of constant concentration. The effect on the deposition of dilution of the bulk solution in contact with the surface was also investigated by gradual replacement of the bulk solution with 1 mM aqueous NaCl. An adsorbed layer remained after complete exchange of the polyelectrolyte/surfactant solution for aqueous NaCl. In most cases, there was a codeposition of silicone oil droplets, if such droplets were present in the formulation before dilution. The overall features of the deposition were similar at hydrophobic and hydrophilic surfaces, but there were also notable differences. SDS molecules adsorbed selectively at the hydrophobized silica surface, but not at the hydrophilic silica, which influenced the coadsorption of the cationic polymers. The largest amount of deposited material after dilution was found for hydrophilic silica and for the least-hydrophobic cationic polymers. For the least-hydrophobic polyions, no significant codeposition of silicone oil was detected at hydrophobized silica after dilution if the initial SDS concentration was high.
|
|
| 31. |
- Dymond, Marcus K., et al.
(författare)
-
Lipid Spontaneous Curvatures Estimated from Temperature-Dependent Changes in Inverse Hexagonal Phase Lattice Parameters : Effects of Metal Cations
- 2016
-
Ingår i: Langmuir. - : American Chemical Society (ACS). - 0743-7463 .- 1520-5827. ; 32:39, s. 10083-10092
-
Tidskriftsartikel (refereegranskat)abstract
- Recently we reported a method for estimating the spontaneous curvatures of lipids from temperature-dependent changes in the lattice parameter of inverse hexagonal liquid crystal phases of binary lipid mixtures. This method makes use of 1,2-dioleoyl-sn-glycerol-3-phosphoethanolamine (DOPE) as a host lipid, which preferentially forms an inverse hexagonal phase to which a guest lipid of unknown spontaneous curvature is added. The lattice parameters of these binary lipid mixtures are determined by small-angle X-ray diffraction at a range of temperatures and the spontaneous curvature of the guest lipid is determined from these data. Here we report the use of this method on a wide range of lipids under different ionic conditions. We demonstrate that our method provides spontaneous curvature values for DOPE, cholesterol, and monoolein that are within the range of values reported in the literature. Anionic lipids 1,2-dioleoyl-sn-glycerol-3-phosphatidic acid (DOPA) and 1,2-dioleoyl-sn-glycerol-3-phosphoserine (DOPS) were found to exhibit spontaneous curvatures that depend on the concentration of divalent cations present in the mixtures. We show that the range of curvatures estimated experimentally for DOPA and DOPS can be explained by a series of equilibria arising from lipid-cation exchange reactions. Our data indicate a universal relationship between the spontaneous curvature of a lipid and the extent to which it affects the lattice parameter of the hexagonal phase of DOPE when it is part of a binary mixture. This universal relationship affords a rapid way of estimating the spontaneous curvatures of lipids that are expensive, only available in small amounts, or are of limited chemical stability.
|
|
| 32. |
- Engström, C, et al.
(författare)
-
Anticipation in unipolar affective disorder.
- 1995
-
Ingår i: Journal of Affective Disorders. - 0165-0327 .- 1573-2517. ; 35:1-2, s. 31-40
-
Tidskriftsartikel (refereegranskat)abstract
- Anticipation describes an inheritance pattern within a pedigree with an increase in disease severity and/or decrease in age at onset in successive generations. The phenomenon of anticipation has recently been shown to be correlated with the expansion of trinucleotide repeat sequences in a neuromuscular disease, various neurodegenerative disorders and mental retardation. We have studied parent-offspring differences in age at onset and disease severity in 31 pairs with unilineal inheritance of unipolar affective disorder (UPAD). Life-table analyses showed a significant decrease in survival to 1st episode of major depression in the offspring generation compared with the parental generation (P = 0.0007). There was also a significant difference in age at onset (P < 0.001) between parents and offsprings. The offspring generation experienced onset 15.6 years earlier and illness 1.5 x more severe than did the parent generation. Furthermore, there was a significant correlation (P < 0.05) in age at onset between parent and offspring generations. When we excluded pairs where the affected parent has an age of onset greater than the age of the child at the time of ascertainment (i.e., 23 pairs left), there was still a significant (P = 0.02) decrease in age at onset (8.4 years) and 1.5 x more severe disease in the offspring generation. No evidence for specific maternal or paternal inheritance was found. We found evidence of anticipation in 75-80% of this sample of unilineal family pairs of UPAD. Anticipation is, thus, an inheritance pattern in a large group of UPAD which suggests that the expansion of trinucleotide repeat sequences is a possible mode of inheritance in this group of UPAD. The findings of anticipation in this study of families with UPAD and previous findings in families with BPAD suggest that the variable expression of unstable expansions of trinucleotide repeats may turn out to be the basis of the continuum of liability in affective disorders.
|
|
| 33. |
- Engström, C, et al.
(författare)
-
Bipolar disorder. II : Personality and age of onset
- 2003
-
Ingår i: Bipolar Disorders. - : Wiley. - 1398-5647 .- 1399-5618. ; 5:5, s. 340-348
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives: The aim of this study was to examine whether personality i.e. temperament and character interacts with age of onset in bipolar disorder. Methods: Bipolar patients were recruited among in- and outpatients from lithium dispensaries of northern Sweden. Patients were diagnosed according to DSM-IV criteria for bipolar disorder type I and II. Temperament and Character Inventory (TCI) was used for measuring personality. TCI was administered to 100 lithium treated bipolar patients and 100 controls. Results: Treatment response was significantly lower (p = 0.005) in patients with early onset compared with late onset. Family history (p = 0.013) and suicide attempts (p = 0.001) were also significantly more common in patients with early onset. Further, patients with early onset were significantly higher (p = 0.045) in the temperament factor harm avoidance (HA) than patients with late onset, but the difference was weak. Patients with early onset had more fear of uncertainty (HA2, P = 0.022) and were more shy (HA3, p = 0.030). Bipolar I patients showed similar results as those in the total bipolar group (I and II), with significantly higher HA (p = 0.019, moderate difference), HA2 (p = 0.015) and HA3 (p = 0.043) in patients with early onset compared with late onset. Bipolar II patients showed no differences between early and late age of onset but the groups are small and the results are therefore uncertain. Conclusions: Early age of onset in bipolar disorder was correlated to an increase in severity, family history, poorer treatment response and poorer prognosis. Early onset was also correlated to personality.
|
|
| 34. |
- Gillams, Richard J., et al.
(författare)
-
Formation of Inverse Topology Lyotropic Phases in Dioleoylphosphatidylcholine/Oleic Acid and Dioleoylphosphatidylethanolamine/Oleic Acid Binary Mixtures
- 2014
-
Ingår i: Langmuir. - : American Chemical Society (ACS). - 0743-7463 .- 1520-5827. ; 30:12, s. 3337-3344
-
Tidskriftsartikel (refereegranskat)abstract
- The addition of saturated fatty acids (FA) to phosphatidylcholine lipids (PC) that have saturated acyl chains has been shown to promote the formation of lyotropic liquidcrystalline phases with negative mean curvature. PC/FA mixtures may exhibit inverse bicontinuous cubic phases (Im3m, Pn3m) or inverse topology hexagonal phases (HII), depending on the length of the acyl chains/fatty acid. Here we report a detailed study of the phase behavior of binary mixtures of dioleoylphosphatidylcholine (DOPC)/oleic acid (OA) and dioleoylphosphatidylethanolamine (DOPE)/oleic acid at limiting hydration, constructed using small-angle X-ray diffraction (SAXD) data. The phase diagrams of both systems show a succession of phases with increasing negative mean curvature with increasing OA content. At high OA concentrations, we have observed the occurrence of an inverse micellar Fd3m phase in both systems. Hitherto, this phase had not been reported for phosphatidylethanolamine/fatty acid mixtures, and as such it highlights an additional route through which fatty acids may increase the propensity of bilayer lipid membranes to curve. We also propose a method that uses the temperature dependence of the lattice parameters of the HII phases to estimate the spontaneous radii of curvature (R0) of the binary mixtures and of the component lipids. Using this method, we calculated the R0 values of the complexes comprising one phospholipid molecule and two fatty acid molecules, which have been postulated to drive the formation of inverse phases in PL/FA mixtures. These are −1.8 nm (±0.4 nm) for DOPC(OA)2 and −1.1 nm (±0.1 nm) for DOPE(OA)2. R0 values estimated in this way allow the quantification of the contribution that different lipid species make to membrane curvature elastic properties and hence of their effect on the function of membrane-bound proteins.
|
|
| 35. |
- Granholm, Linnea, et al.
(författare)
-
Impact of adolescent ethanol exposure and adult amphetamine self-administration on evoked striatal dopamine release in male rats
- 2015
-
Ingår i: Psychopharmacology. - : Springer Science and Business Media LLC. - 0033-3158 .- 1432-2072. ; 232:24, s. 4421-4431
-
Tidskriftsartikel (refereegranskat)abstract
- Adolescent binge drinking is common and associated with increased risk of substance use disorders. Transition from recreational to habitual ethanol consumption involves alterations in dorsal striatal function, but the long-term impact of adolescent ethanol exposure upon this region remains unclear. This study aimed to characterise and describe relationships between adolescent ethanol exposure, amphetamine self-administration and adult dopamine dynamics in dorsal striatum, including response to amphetamine challenge, in male Wistar rats. Ethanol (2 g/kg) or water was administered intragastrically in an episodic binge-like regimen (three continuous days/week) between 4 and 9 weeks of age (i.e. post-natal days 28-59). In adulthood, animals were divided into two groups. In the first, dorsal striatal potassium-evoked dopamine release was examined via chronoamperometry, in the basal state and after a single amphetamine challenge (2 mg/kg, i.v.). In the second, amphetamine self-administration behaviour was studied (i.e. fixed and progressive ratio) before chronoamperometric analysis was conducted as described above. Adolescent ethanol exposure suppressed locally evoked dopamine response after amphetamine challenge in adulthood, whereas in the basal state, no differences in dopamine dynamics were detected. Ethanol-exposed animals showed no differences in adult amphetamine self-administration behaviour but an abolished effect on dopamine removal in response to a single amphetamine challenge after self-administration. Amphetamine challenges in adult rats revealed differences in in vivo dopamine function after adolescent ethanol exposure. The attenuated drug response in ethanol-exposed animals may affect habit formation and contribute to increased risk for substance use disorders as a consequence of adolescent ethanol.
|
|
| 36. |
|
|
| 37. |
|
|
| 38. |
|
|
| 39. |
- Hammarberg, Anders, et al.
(författare)
-
The effect of acamprosate on alcohol craving and correlation with hypothalamic pituitary adrenal (HPA) axis hormones and beta-endorphin
- 2009
-
Ingår i: Brain Research. - : Elsevier BV. - 0006-8993 .- 1872-6240. ; 1305:Suppl., s. S2-S6
-
Tidskriftsartikel (refereegranskat)abstract
- Acamprosate is a widely utilized, efficacious treatment for relapse prevention in alcohol dependent patients. The mechanism of acamprosate action is hypothesized to be by modulation of craving responses. Previous research has suggested that acamprosate may affect the hypothalamic pituitary adrenal (HPA) axis as well as beta-endorphin. The aim of the present study was to investigate if acamprosate attenuates alcohol craving following a short-term treatment, and if craving and drinking measures are correlated to changes in HPA-axis hormones and beta-endorphin. In a double-blind design, 56 alcohol dependent treatment seeking patients were randomized to 21 days of either acamprosate (1998 mg/day) or placebo treatment. Subjective, physiological and biological measurements were recorded at inclusion and on day 21. The results showed that acamprosate treated patients showed significantly reduced craving compared to placebo. Further, a significant correlation was shown between craving and alcohol consumption during study. No changes in hormonal levels were found in acamprosate treated patients compared to placebo.
|
|
| 40. |
- Herrera-Marschitz, M, et al.
(författare)
-
On the origin of extracellular glutamate levels monitored in the basal ganglia of the rat by in vivo microdialysis
- 1996
-
Ingår i: Journal of Neurochemistry. - : Wiley. - 0022-3042 .- 1471-4159. ; 66:4, s. 1726-1735
-
Tidskriftsartikel (refereegranskat)abstract
- Several putative neurotransmitters and metabolites were monitored simultaneously in the extracellular space of neostriatum, substantia nigra, and cortex and in subcutaneous tissue of the rat by in vivo microdialysis. Glutamate (Glu) and aspartate (Asp) were at submicromolar and gamma-aminobutyric acid (GABA) was at nanomolar concentrations in all brain regions. The highest concentration of dopamine (DA) was in the neostriatum. Dynorphin B (Dyn B) was in the picomolar range in all brain regions. Although no GABA, DA, or Dyn B could be detected in subcutaneous tissue, Glu and Asp levels were 5 and approximately 5 and approximately 0.4 microM, respectively. Lactate and pyruvate concentrations were approximately 200 and approximately 10 microM in all regions. The following criteria were applied to ascertain the neuronal origin of substances quantified by microdialysis: sensitivity to (a) K+ depolarization, (b) Na+ channel blockade, (c) removal of extracellular Ca2+, and (d) depletion of presynaptic vesicles by local administration of alpha-latrotoxin. DA, Dyn B, and GABA largely satisfied all these criteria. In contrast, Glu and Asp levels were not greatly affected by K+ depolarization and were increased by perfusing with tetrodotoxin or with Ca2+-free medium, arguing against a neuronal origin. However, Glu and Asp, as well as DA and GABA, levels were decreased under both basal and K+-depolarizing conditions by alpha-latrotoxin. Because the effect of K+ depolarization on Glu and Asp could be masked by reuptake into nerve terminals and glial cells, the reuptake blocker dihydrokainic acid (DHKA) or L-trans-pyrrolidine-2,4-dicarboxylic acid (PDC) was included in the microdialysis perfusion medium. The effect of K+ depolarization on Glu and Asp levels was increased by DHKA, but GABA levels were also affected. In contrast, PDC increased only Glu levels. It is concluded that there is pool of releasable Glu and Asp in the rat brain. However, extracellular levels of amino acids monitored by in vivo microdialysis reflect the balance between neuronal release and reuptake into surrounding nerve terminals and glial elements.
|
|
| 41. |
- Hillarp, Birgitta, et al.
(författare)
-
Myotonic dystrophy revealed at videoradiography of deglutition and speech in adult patients with velopharyngeal insufficiency: presentation of four cases
- 1994
-
Ingår i: Cleft Palate Journal. - 0009-8701. ; 31:2, s. 125-133
-
Tidskriftsartikel (refereegranskat)abstract
- Patients with velopharyngeal insufficiency (VPI) without cleft palate, who appear for the first time in adulthood for treatment, will probably reveal a high percentage of undiagnosed myotonic dystrophy (MD). Videoradiography of deglutition and speech reveals the diagnosis. Eleven adult noncleft palate patients with VPI were studied with videoradiography of the pharynx and esophagus. Three exhibited functional radiographic manifestations of MD during deglutition and speech. The diagnosis confirmed by neurologic examination was not known or suspected prior to videoradiography. An additional patient with VPI and suspected MD displayed the same constellation of radiographic findings. Follow-up examinations confirmed the diagnosis of MD. Three of the four patients had had symptoms of VPI since childhood, but none had complaints of deglutition problems except for accidental nasal regurgitations.
|
|
| 42. |
- Holt, Carl, et al.
(författare)
-
Mineralisation of soft and hard tissues and the stability of biofluids.
- 2014
-
Ingår i: Journal of Structural Biology. - : Elsevier BV. - 1095-8657 .- 1047-8477. ; 185:3, s. 383-396
-
Tidskriftsartikel (refereegranskat)abstract
- Evidence is provided from studies on natural and artificial biofluids that the sequestration of amorphous calcium phosphate by peptides or proteins to form nanocluster complexes is of general importance in the control of physiological calcification. A naturally occurring mixture of osteopontin peptides was shown, by light and neutron scattering, to form calcium phosphate nanoclusters with a core-shell structure. In blood serum and stimulated saliva, an invariant calcium phosphate ion activity product was found which corresponds closely in form and magnitude to the ion activity product observed in solutions of these osteopontin nanoclusters. This suggests that types of nanocluster complexes are present in these biofluids as well as in milk. Precipitation of amorphous calcium phosphate from artificial blood serum, urine and saliva was determined as a function of pH and the concentration of osteopontin or casein phosphopeptides. The position of the boundary between stability and precipitation was found to agree quantitatively with the theory of nanocluster formation. Artificial biofluids were prepared that closely matched their natural counterparts in calcium and phosphate concentrations, pH, saturation, ionic strength and osmolality. Such fluids, stabilised by a low concentration of sequestering phosphopeptides, were found to be highly stable and may have a number of beneficial applications in medicine.
|
|
| 43. |
- Jing, Lin, et al.
(författare)
-
Thermal Conductivity Enhancement of Coaxial Carbon@Boron Nitride Nanotube Arrays
- 2017
-
Ingår i: ACS Applied Materials & Interfaces. - : American Chemical Society (ACS). - 1944-8252 .- 1944-8244. ; 9:17, s. 14555-14560
-
Tidskriftsartikel (refereegranskat)abstract
- We demonstrate the thermal conductivity enhancement of the vertically aligned carbon nanotube (CNT) arrays (from ?15.5 to 29.5 W/mK, ?90% increase) by encapsulating outer boron nitride nanotube (BNNT, 0.97 nm-thick with ?3-4 walls). The heat transfer enhancement mechanism of the coaxial C@BNNT was further revealed by molecular dynamics simulations. Because of their highly coherent lattice structures, the outer BNNT serves as additional heat conducting path without impairing the thermal conductance of inner CNT. This work provides deep insights into tailoring the heat transfer of arbitrary CNT arrays and will enable their broader applications as thermal interface material.
|
|
| 44. |
- Johnson, Eric S., et al.
(författare)
-
Polymer-Surfactant Phase and Surface Interactions Leading to New Models for Cationic Polymer Chemistries
- 2010
-
Ingår i: IFSCC Magazine. - 1520-4561. ; 3,4, s. 1-9
-
Tidskriftsartikel (refereegranskat)abstract
- Cationic polymers are used in anionic surfactant formulations to deposit and co-deposit actives on hair or skin surfaces. A series of cationic polymers, natural and synthetic, were investigated with surface and bulk techniques, turbidity measurements and in situ null-ellipsometry on silica surfaces in order to understand three key areas: the relation between the complex that is formed at a surface and the concentrated phase in the bulk solution, the relation between molecular adsorption of cationic polymer and/or surfactant and co-deposition of actives like silicone emulsions, and the optimization of the formulation to achieve maximum deposition to drive product performance. Key findings were: (1) under most conditions an adsorbed layer of polymer and/ or surfactant is formed at the surface, but this depends greatly on the phase separation in the bulk, (2) the adsorbed amount and ability to deposit actives follows the variation in bulk phase separation because both events are governed by the cationic polymersurfactant binding isotherm, and (3) the hydrophobicity of the cationic polymer can be used to adjust the range of surfactant concentrations to where a maximum phase separation and adsorption is obtained. This led to a model for the development of a new cationic polymer, polyquaterium-76, which delivers superior wet and dry conditioning.
|
|
| 45. |
- Johnston, S. Claiborne, et al.
(författare)
-
Ischemic Benefit and Hemorrhage Risk of Ticagrelor-Aspirin Versus Aspirin in Patients With Acute Ischemic Stroke or Transient Ischemic Attack
- 2021
-
Ingår i: Stroke. - : Wolters Kluwer. - 0039-2499 .- 1524-4628. ; 52:11, s. 3482-3489
-
Tidskriftsartikel (refereegranskat)abstract
- Background and Purpose: In patients with acute mild-moderate ischemic stroke or high-risk transient ischemic attack, the THALES trial (Acute Stroke or Transient Ischemic Attack Treated With Ticagrelor and Aspirin for Prevention of Stroke and Death) demonstrated that when added to aspirin, ticagrelor reduced stroke or death but increased risk of severe hemorrhage compared with placebo. The primary efficacy outcome of THALES included hemorrhagic stroke and death, events also counted in the primary safety outcome. We sought to disentangle risk and benefit, assess their relative impact, and attempt to identify subgroups with disproportionate risk or benefit. Methods: In a randomized, placebo-controlled, double-blind trial of patients with mild-to-moderate acute noncardioembolic ischemic stroke or high-risk transient ischemic attack, patients were randomized within 24 hours after symptom onset to a 30-day regimen of either ticagrelor plus aspirin or matching placebo plus aspirin. For the present analyses, we defined the efficacy outcome, major ischemic events, as the composite of ischemic stroke or nonhemorrhagic death, and defined the safety outcome, major hemorrhage, as intracranial hemorrhage or hemorrhagic death. Net clinical impact was defined as the combination of these 2 end points. Results: In 11 016 patients (5523 ticagrelor-aspirin and 5493 aspirin), a major ischemic event occurred in 294 patients (5.3%) in the ticagrelor-aspirin group and in 359 patients (6.5%) in the aspirin group (absolute risk reduction 1.19% [95% CI, 0.31%-2.07%]). Major hemorrhage occurred in 22 patients (0.4%) in the ticagrelor-aspirin group and 6 patients (0.1%) in the aspirin group (absolute risk increase 0.29% [95% CI, 0.10%-0.48%]). Net clinical impact favored ticagrelor-aspirin (absolute risk reduction 0.97% [95% CI, 0.08%-1.87%]). Findings were similar when different thresholds for disability were applied and over a range of predefined subgroups. Conclusions: In patients with mild-moderate ischemic stroke or high-risk transient ischemic attack, ischemic benefits of 30-day treatment with ticagrelor-aspirin outweigh risks of hemorrhage. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03354429.
|
|
| 46. |
- Kalnina, Liga, et al.
(författare)
-
Body fat in children and adolescents participating in organized sports: Descriptive epidemiological study of 6048 Latvian athletes
- 2015
-
Ingår i: Scandinavian Journal of Public Health. - : SAGE PUBLICATIONS LTD. - 1403-4948 .- 1651-1905. ; 43:6, s. 615-622
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Pressure among young athletes to meet body composition goals may lead to poor nutrition and affect growth. Aims: To examine the proportion of body fat (%BF), measured by bioimpedance analysis, among Latvian children and adolescents participating in organized sports. Methods: Our study had a nationally representative sample of 6048 young athletes, aged 10-17 years. Their %BF was measured using a multifrequency, 8-pole, bioelectrical impedance leg-to-hand analyzer. Results: About 19.2% (CI 14.4-20.0) of boys and 15.1% (CI 14.0-16.3) of girls had a %BF value below the recommended levels. The %BF in young female athletes participating in aesthetic sports was lower than among their peers participating in other sports. Young male athletes participating in aesthetic sports had lower %BF levels at 10 and 12 years of age, compared with participants in weight-class sports; and lower levels of %BF from age 10-14 years, compared with participants in non-weight-sensitive sports. Conclusions: Almost every fifth child and adolescent participating in organized sports displayed critically low body fat levels. Body fat needs to be assessed regularly in young athletes, to prevent negative consequences on health.
|
|
| 47. |
- Karakostis, Konstantinos, et al.
(författare)
-
p53 mRNA and p53 Protein Structures Have Evolved Independently to Interact with MDM2
- 2016
-
Ingår i: Molecular biology and evolution. - : Oxford University Press (OUP). - 0737-4038 .- 1537-1719. ; 33:5, s. 1280-1292
-
Tidskriftsartikel (refereegranskat)abstract
- The p53 tumor suppressor and its key regulator MDM2 play essential roles in development, ageing, cancer, and cellular stress responses in mammals. Following DNA damage, MDM2 interacts with p53 mRNA in an ATM kinase-dependent fashion and stimulates p53 synthesis, whereas under normal conditions, MDM2 targets the p53 protein for degradation. The peptide-and RNA motifs that interact with MDM2 are encoded by the same conserved BOX-I sequence, but how these interactions have evolved is unknown. Here, we show that a temperature-sensitive structure in the invertebrate Ciona intestinalis (Ci) p53 mRNA controls its interaction with MDM2. We also show that a nonconserved flanking region of Ci-BOX-I domain prevents the p53-MDM2 protein-protein interaction. These results indicate that the temperature-regulated p53 mRNA-MDM2 interaction evolved to become kinase regulated in the mammalian DNA damage response. The data also suggest that the negative regulation of p53 by MDM2 via protein-protein interaction evolved in vertebrates following changes in the BOX-I flanking sequence.
|
|
| 48. |
- Kragelund, C., et al.
(författare)
-
Scandinavian fellowship for oral pathology and oral medicine : guidelines for oral pathology and oral medicine in the dental curriculum
- 2012
-
Ingår i: European journal of dental education. - Hoboken : Wiley-Blackwell. - 1396-5883 .- 1600-0579. ; 16:4, s. 246-253
-
Tidskriftsartikel (refereegranskat)abstract
- In Scandinavia, as in many European countries, most patients consult their general dentist once a year or more. This gives the dentist a unique opportunity and an obligation to make an early diagnosis of oral diseases, which is beneficial for both the patient and the society. Thus, the dentist must have knowledge of clinical symptoms, local and systemic signs and clinical differential diagnoses to make an accurate diagnosis. The dentist must be competent in selecting appropriate diagnostic tests, for example, tissue biopsy and microbiological samples, and conducting them correctly, as well as in interpreting test results and taking appropriate action accordingly. Furthermore, the dentist must be aware of diseases demanding multidisciplinary cooperation and be able to recognise his/her professional limitation, and to refer to other specialists when required. The dental curriculum changes over time as new approaches, treatments and diagnostic possibilities develop. Likewise, the role of the dentist in the community changes and may vary in different countries. As members of the Scandinavian Fellowship for Oral Pathology and Oral Medicine and subject representatives of oral pathology and oral medicine, we feel obliged to contribute to the discussion of how the guidelines of the dental curriculum support the highest possible standards of dental education. This article is meant to delineate a reasonable standard of oral pathology and oral medicine in the European dental curriculum and to guide subject representatives in curriculum development and planning. We have created an advisory topic list in oral pathology and oral medicine.
|
|
| 49. |
|
|
| 50. |
|
|
