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Search: WFRF:(Neal Bradley Stephen)

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1.
  • Johansson, Mattias, et al. (author)
  • The influence of obesity-related factors in the etiology of renal cell carcinoma—A mendelian randomization study
  • 2019
  • In: PLoS Medicine. - : Public Library of Science (PLoS). - 1549-1277 .- 1549-1676. ; 16:1
  • Journal article (peer-reviewed)abstract
    • Background: Several obesity-related factors have been associated with renal cell carcinoma (RCC), but it is unclear which individual factors directly influence risk. We addressed this question using genetic markers as proxies for putative risk factors and evaluated their relation to RCC risk in a mendelian randomization (MR) framework. This methodology limits bias due to confounding and is not affected by reverse causation.Methods and findings: Genetic markers associated with obesity measures, blood pressure, lipids, type 2 diabetes, insulin, and glucose were initially identified as instrumental variables, and their association with RCC risk was subsequently evaluated in a genome-wide association study (GWAS) of 10,784 RCC patients and 20,406 control participants in a 2-sample MR framework. The effect on RCC risk was estimated by calculating odds ratios (ORSD) for a standard deviation (SD) increment in each risk factor. The MR analysis indicated that higher body mass index increases the risk of RCC (ORSD: 1.56, 95% confidence interval [CI] 1.44–1.70), with comparable results for waist-to-hip ratio (ORSD: 1.63, 95% CI 1.40–1.90) and body fat percentage (ORSD: 1.66, 95% CI 1.44–1.90). This analysis further indicated that higher fasting insulin (ORSD: 1.82, 95% CI 1.30–2.55) and diastolic blood pressure (DBP; ORSD: 1.28, 95% CI 1.11–1.47), but not systolic blood pressure (ORSD: 0.98, 95% CI 0.84–1.14), increase the risk for RCC. No association with RCC risk was seen for lipids, overall type 2 diabetes, or fasting glucose.Conclusions: This study provides novel evidence for an etiological role of insulin in RCC, as well as confirmatory evidence that obesity and DBP influence RCC risk.
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2.
  • Masci, Lorenzo, et al. (author)
  • Achilles Scraping and Plantaris Tendon Removal Improves Pain and Tendon Structure in Patients with Mid-Portion Achilles Tendinopathy-A 24 Month Follow-Up Case Series
  • 2021
  • In: Journal of Clinical Medicine. - : MDPI. - 2077-0383. ; 10:12
  • Journal article (peer-reviewed)abstract
    • Background: Studies have demonstrated that a sub-group of patients with medial Achilles pain exhibit Achilles tendinopathy with plantaris tendon involvement. This clinical condition is characterised by structural relationships and functional interference between the two tendons, resulting in compressive or shearing forces. Surgical plantaris tendon removal together with an Achilles scraping procedure has demonstrated positive short-term clinical results. The aim of this case series was to determine the long-term outcomes on pain and Achilles tendon structure. Methods: 18 consecutive patients (13 males; 5 females; mean age 39 years; mean symptom duration 28 months), of which three were elites, were included. Clinical examination, b-mode ultrasound (US) and Ultrasound Tissue Characterisation (UTC) confirmed medial Achilles tendon pain and tenderness, medial Achilles tendinopathy plus a plantaris tendon located close to the medial side of the Achilles tendon. Patients underwent US-guided local Achilles scraping and plantaris tendon removal followed by a structured rehabilitation program. Outcomes were VISA-A score for pain and function and UTC for Achilles structure. Results: 16 of 18 patients completed the 24 months follow-up. Mean VISA-A scores increased from 58.2 (±15.9) to 92.0 (±9.2) (mean difference = 33.8, 95% CI 25.2, 42.8, p < 0.01). There was an improvement in Achilles structure with mean organised echo pixels (UTC type I+II, in %) increasing from 79.9 (±11.5) to 86.4 (±10.0) (mean difference = 6.5%, 95% CI 0.80, 13.80, p =0.01), exceeding the 3.4% minimum detectable change. All 16 patients reported satisfaction with the procedure and 14 returned to pre-injury activity levels. There were no reported complications. Conclusions: Improved pain, function and tendon structure were observed 24 months after treatment with Achilles scraping and plantaris excision. The improvement in structure on the medial side of the Achilles after plantaris removal indicates that compression from the plantaris tendon might be an important presenting factor in this sub-group.
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3.
  • Scelo, Ghislaine, et al. (author)
  • Genome-wide association study identifies multiple risk loci for renal cell carcinoma.
  • 2017
  • In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
  • Journal article (peer-reviewed)abstract
    • Previous genome-wide association studies (GWAS) have identified six risk loci for renal cell carcinoma (RCC). We conducted a meta-analysis of two new scans of 5,198 cases and 7,331 controls together with four existing scans, totalling 10,784 cases and 20,406 controls of European ancestry. Twenty-four loci were tested in an additional 3,182 cases and 6,301 controls. We confirm the six known RCC risk loci and identify seven new loci at 1p32.3 (rs4381241, P=3.1 × 10-10), 3p22.1 (rs67311347, P=2.5 × 10-8), 3q26.2 (rs10936602, P=8.8 × 10-9), 8p21.3 (rs2241261, P=5.8 × 10-9), 10q24.33-q25.1 (rs11813268, P=3.9 × 10-8), 11q22.3 (rs74911261, P=2.1 × 10-10) and 14q24.2 (rs4903064, P=2.2 × 10-24). Expression quantitative trait analyses suggest plausible candidate genes at these regions that may contribute to RCC susceptibility.
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