| 1. |
- Boswell, M. T., et al.
(författare)
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Intrahost evolution of the HIV-2 capsid correlates with progression to AIDS
- 2022
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Ingår i: Virus Evolution. - : Oxford University Press (OUP). - 2057-1577. ; 8:2
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Tidskriftsartikel (refereegranskat)abstract
- HIV-2 infection will progress to AIDS in most patients without treatment, albeit at approximately half the rate of HIV-1 infection. HIV-2 capsid (p26) amino acid polymorphisms are associated with lower viral loads and enhanced processing of T cell epitopes, which may lead to protective Gag-specific T cell responses common in slower progressors. Lower virus evolutionary rates, and positive selection on conserved residues in HIV-2 env have been associated with slower progression to AIDS. In this study we analysed 369 heterochronous HIV-2 p26 sequences from 12 participants with a median age of 30 years at enrolment. CD4% change over time was used to stratify participants into relative faster and slower progressor groups. We analysed p26 sequence diversity evolution, measured site-specific selection pressures and evolutionary rates, and determined if these evolutionary parameters were associated with progression status. Faster progressors had lower CD4% and faster CD4% decline rates. Median pairwise sequence diversity was higher in faster progressors (5.7x10-3 versus 1.4x10-3 base substitutions per site, P<0.001). p26 evolved under negative selection in both groups (dN/dS=0.12). Median virus evolutionary rates were higher in faster than slower progressors – synonymous rates: 4.6x10-3 vs. 2.3x10-3; and nonsynonymous rates: 6.9x10-4 vs. 2.7x10-4 substitutions/site/year, respectively. Virus evolutionary rates correlated negatively with CD4% change rates (ρ = -0.8, P=0.02), but not CD4% level. The signature amino acid at p26 positions 6, 12 and 119 differed between faster (6A, 12I, 119A) and slower (6G, 12V, 119P) progressors. These amino acid positions clustered near to the TRIM5α/p26 hexamer interface surface. p26 evolutionary rates were associated with progression to AIDS and were mostly driven by synonymous substitutions. Nonsynonymous evolutionary rates were an order of magnitude lower than synonymous rates, with limited amino acid sequence evolution over time within hosts. These results indicate HIV-2 p26 may be an attractive therapeutic target.
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| 2. |
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| 3. |
- Esbjörnsson, A-C, et al.
(författare)
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Quantifying gait deviations in individuals with rheumatoid arthritis using the Gait Deviation Index
- 2014
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Ingår i: Scandinavian Journal of Rheumatology. - : Informa Healthcare. - 0300-9742 .- 1502-7732. ; 43:2, s. 124-131
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: In this study we evaluated the usability of the Gait Deviation Index (GDI), an index that summarizes the amount of deviation in movement from a standard norm, in adults with rheumatoid arthritis (RA). The aims of the study were to evaluate the ability of the GDI to identify gait deviations, assess inter-trial repeatability, and examine the relationship between the GDI and walking speed, physical disability, and pain.METHOD: Sixty-three adults with RA and 59 adults with typical gait patterns were included in this retrospective case-control study. Following a three-dimensional gait analysis (3DGA), representative gait cycles were selected and GDI scores calculated. To evaluate the effect of walking speed, GDI scores were calculated using both a free-speed and a speed-matched reference set. Physical disability was assessed using the Health Assessment Questionnaire (HAQ) and subjects rated their pain during walking.RESULTS: Adults with RA had significantly increased gait deviations compared to healthy individuals, as shown by lower GDI scores [87.9 (SD = 8.7) vs. 99.4 (SD = 8.3), p < 0.001]. This difference was also seen when adjusting for walking speed [91.7 (SD = 9.0) vs. 99.9 (SD = 8.6), p < 0.001]. It was estimated that a change of ≥ 5 GDI units was required to account for natural variation in gait. There was no evident relationship between GDI and low/high RA-related physical disability and pain.CONCLUSIONS: The GDI seems to useful for identifying and summarizing gait deviations in individuals with RA. Thus, we consider that the GDI provides an overall measure of gait deviation that may reflect lower extremity pathology and may help clinicians to understand the impact of RA on gait dynamics.
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| 4. |
- Esbjörnsson, M, et al.
(författare)
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Muscle fibre types and enzyme activities after training with local leg ischaemia in man.
- 1993
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Ingår i: Acta Physiologica Scandinavica. - : Wiley. - 0001-6772 .- 1365-201X. ; 148:3, s. 233-41
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Tidskriftsartikel (refereegranskat)abstract
- Eight healthy men performed supine one-legged training on a bicycle ergometer 45 min per leg four times per week for 4 week. The ergometer and lower body were inside a pressure chamber, the opening of which was sealed at the level of the crotch. One leg trained with impeded leg blood flow (I-leg), induced by an increased (50 mmHg) chamber pressure, at the highest tolerable intensity. The contralateral leg trained at the same power under normal pressure (N-leg). Before and after training biopsies were taken from the vastus lateralis of both legs and maximal one-legged exercise tests were executed with both legs. Biopsies were repeated when the subjects had been back to their habitual physical activity for 3 months. Training increased exercise time to exhaustion, but more in the I-leg than in the N-leg. After training, the I-leg had higher activity of citrate synthase (CS), a marker of oxidative capacity, and lower activity of the M-subunit of lactate dehydrogenase isoenzymes. It also had a higher percentage of type-I fibres and a lower percentage of IIB fibres, larger areas of all fibre types and a greater number of capillaries per fibre. It is concluded that ischaemic training changes the muscle metabolic profile in a direction facilitating aerobic metabolism. An altered fibre-type composition may contribute, but is not enough prerequisite for the change.
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| 5. |
- Kaijser, L., et al.
(författare)
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Muscle oxidative capacity and work performance after training under local leg ischemia
- 1990
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Ingår i: Journal of applied physiology. - : American Physiological Society. - 8750-7587 .- 1522-1601. ; 69:2, s. 785-787
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Tidskriftsartikel (refereegranskat)abstract
- Healthy young men executed supine one-legged cycle training four times per week for 4 wk with legs and the cycle ergometer inside a pressure chamber, the opening of which was sealed by a rubber membrane at the level of the crotch. Each training session started by training one leg under ischemic conditions induced by increased chamber pressure (50 mmHg) at the highest intensity tolerable for 45 min. Then the other leg was trained with the same power profile but normal atmospheric chamber pressure. Before and after the training period, both legs executed one-legged exercise tests under both normal and increased chamber pressure and muscle biopsies were taken from the vastus lateralis. Ischemic training increased performance more than normal training, the difference being greater for exercise executed under ischemic conditions. The difference in performance increase between the legs was paralleled by a greater muscle citrate synthase activity in the ischemically than in the normally trained leg.
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| 6. |
- Nduva, George M., et al.
(författare)
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Temporal trends and transmission dynamics of pre-treatment HIV-1 drug resistance within and between risk groups in Kenya, 1986–2020
- 2024
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Ingår i: Journal of Antimicrobial Chemotherapy. - 0305-7453. ; 79:2, s. 287-296
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Tidskriftsartikel (refereegranskat)abstract
- Background: Evidence on the distribution of pre-treatment HIV-1 drug resistance (HIVDR) among risk groups is limited in Africa. We assessed the prevalence, trends and transmission dynamics of pre-treatment HIVDR within and between MSM, people who inject drugs (PWID), female sex workers (FSWs), heterosexuals (HETs) and perinatally infected children in Kenya. Methods: HIV-1 partial pol sequences from antiretroviral-naive individuals collected from multiple sources between 1986 and 2020 were used. Pre-treatment reverse transcriptase inhibitor (RTI), PI and integrase inhibitor (INSTI) mutations were assessed using the Stanford HIVDR database. Phylogenetic methods were used to determine and date transmission clusters. Results: Of 3567 sequences analysed, 550 (15.4%, 95% CI: 14.2–16.6) had at least one pre-treatment HIVDR mutation, which was most prevalent amongst children (41.3%), followed by PWID (31.0%), MSM (19.9%), FSWs (15.1%) and HETs (13.9%). Overall, pre-treatment HIVDR increased consistently, from 6.9% (before 2005) to 24.2% (2016–20). Among HETs, pre-treatment HIVDR increased from 6.6% (before 2005) to 20.2% (2011–15), but dropped to 6.5% (2016–20). Additionally, 32 clusters with shared pre-treatment HIVDR mutations were identified. The majority of clusters had R0 ≥ 1.0, indicating ongoing transmissions. The largest was a K103N cluster involving 16 MSM sequences sampled between 2010 and 2017, with an estimated time to the most recent common ancestor (tMRCA) of 2005 [95% higher posterior density (HPD), 2000–08], indicating propagation over 12 years. Conclusions: Compared to HETs, children and key populations had higher levels of pre-treatment HIVDR. Introduction of INSTIs after 2017 may have abrogated the increase in pre-treatment RTI mutations, albeit in the HET population only. Taken together, our findings underscore the need for targeted efforts towards equitable access to ART for children and key populations in Kenya.
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| 7. |
- Broström, E W, et al.
(författare)
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Change in Gait Deviation Index after anti-tumour necrosis factor-α treatment in individuals with rheumatoid arthritis : a pilot study
- 2013
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Ingår i: Scandinavian Journal of Rheumatology. - : Informa Healthcare. - 0300-9742 .- 1502-7732. ; 42:5, s. 356-361
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Anti-tumour necrosis factor-alpha (TNF-α) inhibitors provide fast, effective resolution of rheumatoid arthritis (RA) inflammation. In this study we aimed to quantify the impact of TNF-α treatment on gait dynamics.METHOD: The sample comprised 16 subjects [11 female, median age 56 (range 48-66) years, median disease duration 9.5 (range 4.6-20.6) years] with RA who met the American College of Rheumatology (ACR) criteria, had lower extremity involvement, did not use walking aids, and had started TNF-α treatment within 1 week of baseline gait analysis. Gait analysis focused on three-dimensional (3D) lower extremity joint kinematics, kinetics, time and distance parameters. The Gait Deviation Index (GDI) and GDI-Kinetic were calculated. Data on gait, disease activity, and physical disability were collected at baseline and at 3.5 months.RESULTS: Following treatment with TNF-α, statistically significant improvements were found in disease activity [using the 28-joint Disease Activity Score based on C-reactive protein (DAS28-CRP); median difference (m(d)) = 2.3, p < 0.01], physical disability [Health Assessment Questionnaire (HAQ) m(d) = 0.4, p < 0.01], and pain during walking [visual analogue scale (VAS) m(d) = 11.0, p < 0.05]. Reductions in gait deviations were noted (GDI m(d) = 3.7, p = 0.04; GDI-Kinetic m(d) = 4.1, p = 0.05) along with reductions in dimensionless time and distance parameters. A moderate to good negative correlation existed between baseline GDI and GDI change scores (r(s) = -0.7, p < 0.01).CONCLUSIONS: Treatment with TNF-α improved gait dynamics in adults with RA. Significant gait deviations were, however, still present after treatment. In this study, GDI and GDI-Kinetic scores appeared to be useful outcome measures to quantify changes in gait deviations after this intervention.
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| 8. |
- Eiken, Ola, et al.
(författare)
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Effects of ischaemic training on force development and fibre-type composition in human skeletal muscle
- 1991
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Ingår i: Clinical Physiology. - 0144-5979 .- 1365-2281. ; 11:1, s. 41-49
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Tidskriftsartikel (refereegranskat)abstract
- Force (peak torque) of m. quadriceps femoris was measured during 60 repeated, voluntary dynamic knee extensions in 10 men before and after a 4-week training regimen of one-legged cycle exercise. Biopsies for histochemical analysis were obtained from the lateral vastus muscle after the training period. One leg was trained with the blood flow to the leg muscles reduced by local supra-atmospheric external pressure of 50 mmHg ('Ischaemic leg, I-leg'). Employing the same work-load profile the other leg was trained at normal atmospheric pressure ('Non-restricted-flow leg, N-leg'). In response to I-training, Maximum Peak Torqued (MPT; the highest torque produced in any contraction) and Initial Peak Torque (IPT; the average peak torque of the initial 12 contractions) decreased by 8% (P less than 0.01) and 9% (P less than 0.001), respectively. Final Peak Torque (FPT; the average peak torque of the final 12 contractions) increased by 13% (P less than 0.05) after I-training. No changes in MPT, IPT or FPT occurred following N-training. After training the proportion of slow-twitch fibres was higher (P less than 0.05) and the mean slow-twitch fibre area was larger (P less than 0.05) in the I-than in the N-trained leg. The results indicate that blood flow-restricted training, in contrast to non-restricted-flow training, decreases maximum voluntary dynamic force, possibly by inducing an increase in the share of the muscle cross-sectional area consisting of slow-twitch fibres. That flow-restricted training improves maintenance of force during short-term local exercise may reflect ischaemically induced changes in the metabolic characteristics of skeletal muscle.
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| 9. |
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| 10. |
- Esbjörnsson, A. C., et al.
(författare)
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Geometrical restoration during total hip arthroplasty is related to change in gait pattern - a study based on computed tomography and three-dimensional gait analysis
- 2021
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Ingår i: BMC Musculoskeletal Disorders. - : Springer Science and Business Media LLC. - 1471-2474. ; 22
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Tidskriftsartikel (refereegranskat)abstract
- Background: The effect of change in hip anatomy on change in gait pattern is not well described in current literature. Therefore, our primary aim was to describe and quantify changes in hip geometry and gait pattern 1 year after total hip arthroplasty (THA) in individuals with hip osteoarthritis. Our secondary aim was to explore the effect of postoperative change in femoral neck anteversion (FNA) and femoral offset and acetabular offset (FO/AO) quota on postoperative change in hip rotation and hip adduction moment during gait, respectively, 1 year after THA”. Methods: Sixty-five individuals with primary hip osteoarthritis, scheduled for THA, were analyzed in this prospective intervention study. Participants were evaluated pre- and 1 year postoperatively with computed tomography-scans, three-dimensional gait analysis, and patient-reported outcome measures. Multiple linear regressions were performed to evaluate the association between change in joint anatomy and change in gait pattern after THA. Results: One year postoperatively, global offset was symmetrical between sides as a result of decreased acetabular offset and increased femoral offset on the operated side. Quality of overall gait pattern improved, and participants walked faster and with less trunk lean over the affected side. FNA and hip rotations during walking changed equally in external and internal directions after THA and change in hip rotation during walking was associated with change in FNA in the same direction. An increase in external hip adduction moments was, on the other hand, not associated with change in FO/AO quota but with a more upright walking position and increased walking speed. Conclusions: The findings of this study suggest that geometrical restoration during THA impacts postoperative gait pattern and, in addition to known factors such as FO, height of hip rotation center, and leg length discrepancy, the FNA must also be taken into consideration. Trial registration: Trial registration: Clinicaltrial.gov, NCT01512550, Registered 19 January 2012 - Retrospectively registered.
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