| 1. |
- Justice, A. E., et al.
(författare)
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Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits
- 2017
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Few genome-wide association studies (GWAS) account for environmental exposures, like smoking, potentially impacting the overall trait variance when investigating the genetic contribution to obesity-related traits. Here, we use GWAS data from 51,080 current smokers and 190,178 nonsmokers (87% European descent) to identify loci influencing BMI and central adiposity, measured as waist circumference and waist-to-hip ratio both adjusted for BMI. We identify 23 novel genetic loci, and 9 loci with convincing evidence of gene-smoking interaction (GxSMK) on obesity-related traits. We show consistent direction of effect for all identified loci and significance for 18 novel and for 5 interaction loci in an independent study sample. These loci highlight novel biological functions, including response to oxidative stress, addictive behaviour, and regulatory functions emphasizing the importance of accounting for environment in genetic analyses. Our results suggest that tobacco smoking may alter the genetic susceptibility to overall adiposity and body fat distribution.
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| 2. |
- Graff, M., et al.
(författare)
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Genome-wide physical activity interactions in adiposity. A meta-analysis of 200,452 adults
- 2017
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Ingår i: PLoS Genet. - : Public Library of Science (PLoS). - 1553-7404 .- 1553-7390. ; 13:4
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Tidskriftsartikel (refereegranskat)abstract
- Physical activity (PA) may modify the genetic effects that give rise to increased risk of obesity. To identify adiposity loci whose effects are modified by PA, we performed genome-wide interaction meta-analyses of BMI and BMI-adjusted waist circumference and waist-hip ratio from up to 200,452 adults of European (n = 180,423) or other ancestry (n = 20,029). We standardized PA by categorizing it into a dichotomous variable where, on average, 23% of participants were categorized as inactive and 77% as physically active. While we replicate the interaction with PA for the strongest known obesity-risk locus in the FTO gene, of which the effect is attenuated by similar to 30% in physically active individuals compared to inactive individuals, we do not identify additional loci that are sensitive to PA. In additional genome-wide meta-analyses adjusting for PA and interaction with PA, we identify 11 novel adiposity loci, suggesting that accounting for PA or other environmental factors that contribute to variation in adiposity may facilitate gene discovery.
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| 3. |
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| 4. |
- Walford, G. A., et al.
(författare)
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Genome-wide association study of the modified stumvoll insulin sensitivity index identifies BCL2 and FAM19A2 as novel insulin sensitivity loci
- 2016
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 65:10, s. 3200-3211
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have found few common variants that influence fasting measures of insulin sensitivity. We hypothesized that a GWAS of an integrated assessment of fasting and dynamic measures of insulin sensitivity would detect novel common variants. We performed a GWAS of the modified Stumvoll Insulin Sensitivity Index (ISI) within the Meta-Analyses of Glucose and Insulin-Related Traits Consortium. Discovery for genetic association was performed in 16,753 individuals, and replication was attempted for the 23 most significant novel loci in 13,354 independent individuals. Association with ISI was tested in models adjusted for age, sex, and BMI and in a model analyzing the combined influence of the genotype effect adjusted for BMI and the interaction effect between the genotype and BMI on ISI (model 3). In model 3, three variants reached genome-wide significance: Rs13422522 (NYAP2; P = 8.87 × 10-11), rs12454712 (BCL2; P = 2.7 × 10-8), and rs10506418 (FAM19A2; P = 1.9 × 10-8). The association at NYAP2 was eliminated by conditioning on the known IRS1 insulin sensitivity locus; the BCL2 and FAM19A2 associations were independent of known cardiometabolic loci. In conclusion, we identified two novel loci and replicated known variants associated with insulin sensitivity. Further studies are needed to clarify the causal variant and function at the BCL2 and FAM19A2 loci. © 2016 by the American Diabetes Association.
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| 6. |
- Lagou, Vasiliki, et al.
(författare)
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Sex-dimorphic genetic effects and novel loci for fasting glucose and insulin variability
- 2021
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Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Differences between sexes contribute to variation in the levels of fasting glucose and insulin. Epidemiological studies established a higher prevalence of impaired fasting glucose in men and impaired glucose tolerance in women, however, the genetic component underlying this phenomenon is not established. We assess sex-dimorphic (73,089/50,404 women and 67,506/47,806 men) and sex-combined (151,188/105,056 individuals) fasting glucose/fasting insulin genetic effects via genome-wide association study meta-analyses in individuals of European descent without diabetes. Here we report sex dimorphism in allelic effects on fasting insulin at IRS1 and ZNF12 loci, the latter showing higher RNA expression in whole blood in women compared to men. We also observe sex-homogeneous effects on fasting glucose at seven novel loci. Fasting insulin in women shows stronger genetic correlations than in men with waist-to-hip ratio and anorexia nervosa. Furthermore, waist-to-hip ratio is causally related to insulin resistance in women, but not in men. These results position dissection of metabolic and glycemic health sex dimorphism as a steppingstone for understanding differences in genetic effects between women and men in related phenotypes.
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| 7. |
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| 8. |
- Alghamdi, N. H., et al.
(författare)
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The Impact of the Degree of Kinesiophobia on Recovery in Patients With Achilles Tendinopathy
- 2021
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Ingår i: Physical Therapy & Rehabilitation Journal. - : Oxford University Press (OUP). - 0031-9023 .- 1538-6724. ; 101:11
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Tidskriftsartikel (refereegranskat)abstract
- Objective Kinesiophobia has been proposed to influence recovery in individuals with Achilles tendinopathy. However, whether there are differences in outcomes in individuals with different levels of kinesiophobia is unknown. The purpose of this study was to compare the characteristics of patients at baseline and recovery over time in individuals with Achilles tendinopathy and various levels of kinesiophobia. Methods This study was a secondary analysis of a prospective observational cohort study of 59 individuals with Achilles tendinopathy. The participants were divided into 3 groups on the basis of scores on the Tampa Scale for Kinesiophobia (TSK) (those with low TSK scores [<= 33; low TSK group], those with medium TSK scores [34-41; medium TSK group], and those with high TSK scores [>= 42; high TSK group]). All participants were evaluated with self-reported outcomes, clinical evaluation, tendon morphology, viscoelastic property measurements, and a calf muscle endurance test at baseline, 6 months, and 12 months. No treatment was provided throughout the study period. Results There were 16 participants (8 women) in the low TSK group (age=51.9 [SD=15.3] years, body mass index [BMI]=24.3 [22.3-25.4]), 28 participants (13 women) in the medium TSK group (age=52.7 [SD=15.2] years, BMI=26.4 [22.5-30.8]), and 15 participants (8 women) in the high TSK group (age=61.1 [SD=11.1] years, BMI=28.1 [25.2-33.6]). Among the groups at baseline, the high TSK group had significantly greater BMI and symptom severity and lower quality of life. All groups showed significant improvement over time for all outcomes except tendon viscoelastic properties and tendon thickening when there was an adjustment for baseline BMI. The high and medium TSK groups saw decreases in kinesiophobia at 6 months, but there was no change for the low TSK group. Conclusion Despite the high TSK group having the highest BMI and the worse symptom severity and quality of life at baseline, members of this group showed improvements in all of the outcome domains similar to those of the other groups over 12 months. Impact Evaluating the degree of kinesiophobia in individuals with Achilles tendinopathy might be of benefit for understanding how they are affected by the injury. However, the degree of kinesiophobia at baseline does not seem to affect recovery; this finding could be due to the patients receiving education about the injury and expectations of recovery.
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| 9. |
- Antza, C., et al.
(författare)
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Prevention of cardiovascular disease in young adults: Focus on gender differences. A collaborative review from the EAS Young Fellows
- 2023
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Ingår i: Atherosclerosis. - 0021-9150. ; 384
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Tidskriftsartikel (refereegranskat)abstract
- A steady rise in cardiovascular morbidity and mortality has been observed in young adults within the last decades. This trend corresponds to an increasing prevalence of traditional cardiovascular risk factors such as obesity and diabetes mellitus type 2 among young adults living in developed countries. Moreover, age-specific risk factors, such as substance abuse, contraceptive medication, and pregnancy-related diseases also correlate with an increased incidence of cardiovascular diseases. In this review, we discuss the available data for young adults on the epidemiology and the rationale for the causality of traditional and newly emerging risk factors of atherosclerotic cardiovascular diseases. We focus on gender-related differences in the exposure to these risk factors, investigate the recent data regarding screening and risk stratification in the young adult population, and describe the current state of the art on lifestyle and therapeutic intervention strategies in the primary prevention setting.
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| 10. |
- Carmont, Michael R, 1972, et al.
(författare)
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Functional Outcomes of Achilles Tendon Minimally Invasive Repair Using 4- and 6-Strand Nonabsorbable Suture: A Cohort Comparison Study
- 2017
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Ingår i: Orthopaedic Journal of Sports Medicine. - : SAGE Publications. - 2325-9671. ; 5:8
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Tidskriftsartikel (refereegranskat)abstract
- Background: The aim of management of Achilles tendon rupture is to reduce tendon lengthening and maximize function while reducing the rerupture rate and minimizing other complications. Purpose: To determine changes in Achilles tendon resting angle (ATRA), heel-rise height, patient-reported outcomes, return to play, and occurrence of complications after minimally invasive repair of Achilles tendon ruptures using nonabsorbable sutures. Methods: Between March 2013 and August 2015, a total of 70 patients (58 males, 12 females) with a mean age of 42 8 years were included and evaluated at 6 weeks and 3, 6, 9, and 12 months after repair of an Achilles tendon rupture. Surgical repair was performed using either 4-strand or 6-strand nonabsorbable sutures. After surgery, patients were mobilized, fully weightbearing using a functional brace. Early active movement was permitted starting at 2 weeks. Results: There were no significant differences in the ATRA, Achilles Tendon Total Rupture Score (ATRS), and Heel-Rise Height Index (HRHI) between the 4- and 6-strand repairs. The mean (SD) relative ATRA was -13.1 degrees (6.6 degrees) (dorsiflexion) following injury; this was reduced to 7.6 degrees (4.8 degrees) (plantar flexion) directly after surgery. During initial rehabilitation at 6 weeks, the relative ATRA was 0.6 degrees (7.4 degrees) (neutral) and -7.0 degrees (5.3 degrees) (dorsiflexion) at 3 months, after which ATRA improved significantly with time to 12 months (P = .005). At 12 months, the median ATRS was 93 (range, 35-100), and the mean (SD) HRHI and Heel-Rise Repetition Index were 81% (0.22%) and 82.9% (0.17%), respectively. The relative ATRA at 3 and 12 months correlated with HRHI (r = 0.617, P < .001 and r = 0.535, P < .001, respectively). Conclusion: Increasing the number of suture strands from 4 to 6 does not alter the ATRA or HRHI after minimally invasive Achilles tendon repair. The use of a nonabsorbable suture during minimally invasive repair when used together with accelerated rehabilitation did not prevent the development of an increased relative ATRA. The ATRA at 3 months after surgery correlated with heel-rise height at 12 months.
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| 11. |
- Escriche-Escuder, A., et al.
(författare)
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Pain neuroscience education in persistent painful tendinopathies: A scoping review from the Tendon PNE Network
- 2023
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Ingår i: Physical Therapy in Sport. - 1466-853X. ; 63, s. 38-49
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Tidskriftsartikel (refereegranskat)abstract
- Objective: to conduct and report a scoping review of the available evidence of the effects and content of pain neuroscience education for patients with persistent painful tendinopathies.Methods: PubMed, Embase, Web of Science, CINAHL, SPORTDiscus, and grey literature databases were searched from database inception to May 2022. Randomised and non-randomised controlled trials, non-controlled clinical trials, cohort studies, case series, case studies including people with persistent painful tendinopathy aged & GE;18 years, a pain education intervention, and in English were included. Studies were excluded if they were crosssectional studies, reviews, editorials, abstracts, or full-text not available or if included heterogeneous study cohorts, patients with tendon rupture, or patients with systemic diseases.Results: five studies (n = 164) were included. Pain neuroscience education entailed face-to-face discussion sessions or educational materials including videos, brochures, paper drawings, and review questions. All studies used pain neuroscience education in conjunction with other interventions, obtaining significant benefits in outcomes related to pain, physical performance, or self-reported function, among others.Conclusions: The application of pain neuroscience education in conjunction with other interventions seemed to improve several outcomes. However, considering the current knowledge about tendon pain and the scarcity of well-designed trials studying pain neuroscience education in tendinopathy, additional research is needed.
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| 13. |
- Smitheman, H. P., et al.
(författare)
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Putting the fear-avoidance model into practice - what can patients with chronic low back pain learn from patients with Achilles tendinopathy and vice versa?
- 2023
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Ingår i: Brazilian Journal of Physical Therapy. - 1413-3555 .- 1809-9246. ; 27:5
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Tidskriftsartikel (refereegranskat)abstract
- Background: Fear-avoidance variables are present in patients with musculoskeletal pain conditions, such as chronic low back pain (CLBP) and Achilles tendinopathy (AT) and can lead to reduced function and recovery. It is unknown how these variables relate in populations with different etiologies but similar pain provocation mechanisms. Objective: To compare kinesiophobia, pain catastrophizing, and disability between these two groups. Methods: Patients with CLBP and those with AT were included. Tampa Scale of Kinesiophobia (TSK-17) and Pain Catastrophizing Scale (PCS-13) were evaluated in both groups. The CLBP group completed the Oswestry Disability Index (ODI) and the AT group completed the PROMIS-29 questionnaire. Gait speed was calculated for each group. Disability outcomes were normalized between groups. Results: 119 patients in the CLBP group (64 female, 46 +/- 8 years) and 83 patients in the AT group (42 female, 48 +/- 12 years) were included. Both groups (CLBP, AT) presented with high prevalence of kinesiophobia (67%, 55%) but the CLBP group presented with higher prevalence of pain cata-strophizing (22%, 2%). The CLBP group demonstrated higher levels of disability via normalized ODI (MD= 12.4, 95% CI: 9.2, 15.5) but the AT group demonstrated slower gait speed (MD= 0.1 m/ s, 95% CI: 0.0, 0.2). Conclusion: Similarly high prevalence of kinesiophobia was found in patients with CLBP and patients with AT. While the CLBP group reported greater prevalence of catastrophizing thoughts and greater disability, the AT group had slower gait speed. Overall, these findings demonstrate that CLBP and AT have similarities that may allow clinicians to learn from one to inform treatment of the other. Clinical Trial Registration Numbers: NCT03523325, ISRCTN17115599. (c) 2023 Associacao Brasileira de Pesquisa e Pos-Graduacao em Fisioterapia. Published by Elsevier Espana, S.L.U. All rights reserved.
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| 15. |
- Vicenzino, Bill, et al.
(författare)
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ICON 2019-International Scientific Tendinopathy Symposium Consensus : There are nine core health-related domains for tendinopathy (CORE DOMAINS): Delphi study of healthcare professionals and patients
- 2020
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Ingår i: British Journal of Sports Medicine. - : BMJ PUBLISHING GROUP. - 0306-3674 .- 1473-0480. ; 54:8, s. 444-451
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe absence of any agreed-upon tendon health-related domains hampers advances in clinical tendinopathy research. This void means that researchers report a very wide range of outcome measures inconsistently. As a result, substantial synthesis/meta-analysis of tendon research findings is almost futile despite researchers publishing busily. We aimed to determine options for, and then define, core health-related domains for tendinopathy.MethodsWe conducted a Delphi study of healthcare professionals (HCP) and patients in a three-stage process. In stage 1, we extracted candidate domains from clinical trial reports and developed an online survey. Survey items took the form: 'The 'candidate domain' is important enough to be included as a core health-related domain of tendinopathy'; response options were: agree, disagree, or unsure. In stage 2, we administered the online survey and reported the findings. Stage 3 consisted of discussions of the findings of the survey at the ICON (International Scientific Tendinopathy Symposium Consensus) meeting. We set 70% participant agreement as the level required for a domain to be considered 'core'; similarly, 70% agreement was required for a domain to be relegated to 'not core' (see Results next).ResultsTwenty-eight HCP (92% of whom had >10 years of tendinopathy experience, 71% consulted >10 cases per month) and 32 patients completed the online survey. Fifteen HCP and two patients attended the consensus meeting. Of an original set of 24 candidate domains, the ICON group deemed nine domains to be core. These were: (1) patient rating of condition, (2) participation in life activities (day to day, work, sport), (3) pain on activity/loading, (4) function, (5) psychological factors, (6) physical function capacity, (7) disability, (8) quality of life and (9) pain over a specified time. Two of these (2, 6) were an amalgamation of five candidate domains. We agreed that seven other candidate domains were not core domains: range of motion, pain on clinician applied test, clinical examination, palpation, drop out, sensory modality pain and pain without other specification. We were undecided on the other five candidate domains of physical activity, structure, medication use, adverse effects and economic impact.ConclusionNine core domains for tendon research should guide reporting of outcomes in clinical trials. Further research should determine the best outcome measures for each specific tendinopathy (ie, core outcome sets).
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