| 91. |
- Olofsson, Tor, et al.
(författare)
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Patient-Reported Outcomes Are More Important Than Objective Inflammatory Markers for Sick Leave in Biologics-Treated Patients With Rheumatoid Arthritis
- 2018
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Ingår i: Arthritis Care and Research. - : Wiley. - 2151-464X .- 2151-4658. ; 70:11, s. 1712-1716
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To study the impact of common noncomposite disease activity measures on sick leave in biologics-treated patients with rheumatoid arthritis (RA). Methods: Data from study visits by biologics-treated RA patients of working age (<65 years) in the observational South Swedish Arthritis Treatment Group Register between 2005 and 2011, were included (5,118 visits by 941 patients). We performed association analyses between various noncomposite disease activity measures at each visit and the number of days of sick leave during the subsequent month; this information was retrieved from the Social Insurance Agency. Adjusted separate generalized estimating equation regression models were used, and analyses were stratified according to sick leave status for the month preceding each visit (no, partial, or full sick leave). Results are presented as standardized beta coefficients for comparability. Results: Among modifiable noncomposite disease activity measures, patient's assessment of pain and disease activity scored on a visual analog scale (VAS) were most strongly associated with subsequent sick leave, irrespective of baseline sick leave status. Generally, measures that were more objective (swollen joint count, erythrocyte sedimentation rate, and C-reactive protein) had less impact on sick leave compared with variables that were more subjective (patient's pain and global scores on a VAS, evaluator's global assessment of disease activity on a 5-grade Likert scale, and tender joint count). Conclusion: Measures of disease activity that are more subjective have a greater impact on sick leave in biologics-treated patients with RA compared with variables that are more objective, suggesting a stronger focus on subjective measures when targeting work loss or intervening to reduce it.
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| 92. |
- Overgaard, Anders, et al.
(författare)
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The implications of an aging population and increased obesity for knee arthroplasty rates in Sweden : a register-based study
- 2020
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Ingår i: Acta Orthopaedica. - : Medical Journals Sweden AB. - 1745-3674 .- 1745-3682. ; 91:6, s. 738-742
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose — Total knee arthroplasty (TKA) has increased substantially in Sweden. We quantified the relative risk for TKA in the Swedish population for different BMI categories and age groups to investigate whether the continued increase in TKA is attributable to increased prevalence of obesity and elderly people in the population, and to put forward model predictions for coming needs for TKA. Patients and methods — We used the Swedish Nationwide Health Survey (SNHS) and the Swedish Knee Arthroplasty Register (SKAR) 2009–2015 to calculate the relative risk (RR) of TKA by age (middle-aged 45–64 years and elderly 65–84 years) and BMI (BMI 18.5–24.9 normal weight; BMI 25.0–29.9 overweight; BMI > 30 obese). The RR for TKA was applied to the demographic forecasts for the Swedish population as a forecasting model. Results — Population size increased 5.2% from 2009 to 2015 to 40,000 middle-aged and 250,000 elderly, and the prevalence of obesity increased from 16% to 18% in these 2 age categories. Compared with those of normal weight, the RR for TKA was 2.7 (95% CI 2.5–3.0) higher for the overweight and 7.3 (6.7–8.0) higher for the obese, aged 45–64. The corresponding figures for individuals aged 65–84 were 2.1 (2.0–2.2) and 4.0 (3.8–4.3) higher, respectively. The changes in the prevalence of obesity and an increase in the elderly population accounted for an estimated increase of 1,700 TKAs over the 7 years. Interpretation — The increase in obesity frequency and the rise in the population of middle-aged and elderly may, to some extent, explain the rise in TKA utilization in Sweden.
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| 93. |
- Pedersen, Soren W., et al.
(författare)
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Probing backbone hydrogen bonding in PDZ/ligand interactions by protein amide-to-ester mutations
- 2014
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 5, s. 3215-
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Tidskriftsartikel (refereegranskat)abstract
- PDZ domains are scaffolding modules in protein-protein interactions that mediate numerous physiological functions by interacting canonically with the C-terminus or non-canonically with an internal motif of protein ligands. A conserved carboxylate-binding site in the PDZ domain facilitates binding via backbone hydrogen bonds; however, little is known about the role of these hydrogen bonds due to experimental challenges with backbone mutations. Here we address this interaction by generating semisynthetic PDZ domains containing backbone amide-to-ester mutations and evaluating the importance of individual hydrogen bonds for ligand binding. We observe substantial and differential effects upon amide-to-ester mutation in PDZ2 of postsynaptic density protein 95 and other PDZ domains, suggesting that hydrogen bonding at the carboxylate-binding site contributes to both affinity and selectivity. In particular, the hydrogen-bonding pattern is surprisingly different between the non-canonical and canonical interaction. Our data provide a detailed understanding of the role of hydrogen bonds in protein-protein interactions.
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| 94. |
- Persson, Fredrik, 1979, et al.
(författare)
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Local conformation of confined DNA studied using emission polarization anisotropy
- 2010
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Ingår i: Biophysical Society 54th Annual Meeting.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- When confined in nanochannels with dimensions smaller than the DNA radius of gyration, DNA will extend along the channel. We investigate long DNA confined in nanochannels, using fluorescence microscopy and intercalated dyes. Studies of the dynamics and statics of DNA in such nanoscale confinements as a function of e.g. degree of confinement and ionic strength have yielded new insights into the physical properties of DNA with relevance for applications in genomics as well as fundamental understanding of DNA packaging in vivo. Our work extends the field by not only studying the location of the emitting dyes along a confined DNA molecule but also monitoring the polarization of the emitted light. By measuring the emission polarized parallel and perpendicular to the extension axis of the stretched DNA, information on the local spatial distribution of the DNA backbone can be obtained. Comparing polarizations in two directions for DNA confined in channels of effective diameters of 85 nm and 170 nm reveals a striking difference. Whereas the DNA in the larger channels shows an isotropic polarization of the emitted light, the light is to a large extent polarized perpendicular to the elongation of the DNA in the smaller channels. We expect this technique to have a large impact on the studies of changes in DNA conformation induced by protein binding or during DNA compactation as well as in fundamental polymer physics studies of DNA in confined environments, for example in bacterial spores and viruses.
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| 95. |
- Persson, Fredrik, 1979, et al.
(författare)
-
Local conformation of confined DNA studied using emission polarization anisotropy
- 2010
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Ingår i: NanoBioTech-Montreux 2009.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- In nanochannels with dimensions smaller than the DNA radius of gyration, DNA will extend along the channel. We investigate long DNA confined in nanochannels using fluorescence microscopy and intercalated dyes. Studies of the dynamics and statics of the DNA extension or position in such nanoscale confinements as a function of e.g. DNA contour length, degree and shape of confinement as well as ionic strength have yielded new insights in the physical properties of DNA with relevance for applications in genomics as well as fundamental understanding of DNA packaging in vivo. Our work extends the field by not only studying the location of the emitting dyes along a confined DNA molecule but also monitoring the polarization of the emitted light. We use intercalating dyes (YOYO-1) whose emission is polarized perpendicular to the DNA extension axis, and by measuring the emission polarized parallel and perpendicular to the extension axis of the stretched DNA, information on the local spatial distribution of the DNA backbone can be obtained. The results obtained are analogous to linear dichroism (LD) but on a single-molecule level, and obtained in a highly parallel fashion. We will discuss results in shallow (60 nm) and deep (180 nm) channels and describe an example of how the technique can be used to investigate non-uniform stretching of DNA on the single molecule level. Comparing polarizations in two directions for DNA confined in channels of effective diameters of 85 nm and 170 nm reveals a striking difference. Whereas the DNA in the larger channels shows an isotropic polarization of the emitted light, the light is to a large extent polarized perpendicular to the elongation of the DNA in the smaller channels. The ratio of the polarization parallel and perpendicular to the elongation direction, I|| / I⊥, is a measure of the relative local orientation of the DNA backbone. We believe that this technique will have a large impact on the studies of changes in DNA conformation induced by protein binding or during DNA compactation as well as in fundamental polymer physics studies of DNA in confined environments, for example in bacterial spores and viruses.
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| 96. |
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| 97. |
- Persson, Fredrik, et al.
(författare)
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Polarization anisotropy of DNA in nanochannels
- 2008
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Ingår i: ; , s. 668-670
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Konferensbidrag (refereegranskat)abstract
- The local alignment of DNA stretched in nanofluidic channels is measured using polarization sensitive detection. With increased degree of stretching the polarization anisotropy increases both in the deGennes and the Odijk regime. The technique is expected to find use in studies of, for example, local conformational changes in polymer physics in confined spaces, studies of protein-DNA interactions and compactation of DNA.
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| 98. |
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| 99. |
- Reisner, Walter, et al.
(författare)
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Directed self-organization of single DNA molecules in a nanoslit via embedded nanopit arrays
- 2009
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Ingår i: Proceedings of the National Academy of Sciences. - : Proceedings of the National Academy of Sciences. - 1091-6490 .- 0027-8424. ; 106:1, s. 79-84
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Tidskriftsartikel (refereegranskat)abstract
- We show that arrays of nanopit structures etched in a nanoslit can control the positioning and conformation of single DNA molecules in nanofluidic devices. By adjusting the spacing, organization and placement of the nanopits it is possible to immobilize DNA at predetermined regions of a device without additional chemical modification and achieve a high degree of control over local DNA conformation. DNA can be extended between two nanopits and in closely spaced arrays will self-assemble into "connect-the-dots" conformations consisting of locally pinned segments joined by fluctuating linkers. These results have broad implications for nanotechnology fields that require methods for the nanoscale positioning and manipulation of DNA.
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| 100. |
- Reisner, Walter, et al.
(författare)
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Nanoconfinement-enhanced conformational response of single DNA molecules to changes in ionic environment
- 2007
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Ingår i: Physical Review Letters. - 1079-7114. ; 99:5
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Tidskriftsartikel (refereegranskat)abstract
- We show that the ionic environment plays a critical role in determining the configurational properties of DNA confined in silica nanochannels. The extension of DNA in the nanochannels increases as the ionic strength is reduced, almost tripling over two decades in ionic strength for channels around 100x100 nm in dimension. Surprisingly, we find that the variation of the persistence length alone with ionic strength is not enough to explain our results. The effect is due mainly to increasing self-avoidance created by the reduced screening of electrostatic interactions at low ionic strength. To quantify the increase in self-avoidance, we introduce a new parameter into the de Gennes theory: an effective DNA width that gives the increase in the excluded volume due to electrostatic repulsion.
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