| 191. |
- Davies, John R, et al.
(author)
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Inherited variation in the PARP1 gene and survival from melanoma
- 2014
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In: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 135:7, s. 1625-1633
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Journal article (peer-reviewed)abstract
- We report the association of an inherited variant located upstream of the poly(adenosine diphosphate-ribose) polymerase 1 (PARP1) gene (rs2249844), with survival in 11 BioGenoMEL melanoma cohorts. The gene encodes a protein involved in a number of cellular processes including single-strand DNA repair. Survival analysis was conducted for each cohort using proportional hazards regression adjusting for factors known to be associated with survival. Survival was measured as overall survival (OS) and, where available, melanoma-specific survival (MSS). Results were combined using random effects meta-analysis. Evidence for a role of the PARP1 protein in melanoma ulceration and survival was investigated by testing gene expression levels taken from formalin-fixed paraffin-embedded tumors. A significant association was seen for inheritance of the rarer variant of PARP1, rs2249844 with OS (hazard ratio (HR) = 1.16 per allele, 95% confidence interval (CI) 1.04-1.28, p=0.005, eleven cohorts) and MSS (HR=1.20 per allele, 95% CI 1.01-1.39, p=0.03, eight cohorts). We report bioinformatic data supportive of a functional effect for rs2249844. Higher levels of PARP1 gene expression in tumors were shown to be associated with tumor ulceration and poorer OS. What's new? Although staging systems predict outcome fairly well for melanoma, survival still varies among individual patients. In this meta-analysis, the authors found that inheritance of a rare genetic variant of PARP1 was associated with improved survival of melanoma patients. Increased expression of PARP1 has been associated with poorer outcome, and depletion of PARP1 may reduce both melanoma growth and angiogenesis. The identification of this and other germline variants that affect survival may help to identify key biological pathways active in host/tumor interactions, which may lead to the discovery of new therapeutic targets for treating advanced melanoma. Epidemiology
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| 192. |
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| 193. |
- Doody, A., et al.
(author)
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Validating the association between plasma tumour necrosis factor receptor 1 levels and the presence of renal injury and functional decline in patients with Type 2 diabetes
- 2018
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In: Journal of Diabetes and Its Complications. - : Elsevier BV. - 1056-8727. ; 32:1, s. 95-99
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Journal article (peer-reviewed)abstract
- Aims: Elevated plasma soluble tumour necrosis factor receptor 1 (TNFR1) predicts long-term progression of chronic kidney disease. We investigated the association between elevated TNFR1 and the presence of renal disease in patients with Type 2 diabetes mellitus registering a haemoglobin Mc (HbA1c) >48 mmol/mol despite medical therapy. Methods: Using sensitivity, specificity and regression analyses we interrogated the association between plasma TNFR1 and presence of chronic kidney disease as assessed by the presence of microalbuminuria and/or an estimated glomerular filtration rate of less than 60 ml/min/1.73 m(2) (stages 3-5 chronic kidney disease). The association of TNFR1 with C-reactive protein and leptin-adiponectin ratio as plasma markers of systemic inflammation and adipose stress respectively was also investigated. Results: Upper quartile TNFR1 is independently associated with elevated urinary albumin-creatinine ratios, reductions in eGFR and strongly predicts the presence of stages 3-5 chronic kidney disease in regression modelling. Elevated TNFR1 levels are associated with increased plasma C-reactive protein and augmented leptin-adiponectin ratio. Conclusions: Our study confirms plasma TNFR1 as a surrogate of renal structural and functional impairment in patients with type 2 diabetes mellitus. Association of TNFR1 with markers of systemic inflammation and adipose stress indicates that TNFR1 may be a biomarker of these processes as components of the pathogenesis of diabetic kidney disease. (C) 2017 Elsevier Inc. All rights reserved.
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| 194. |
- dos Reis, Fabio Bueno, Jr., et al.
(author)
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Nodulation and nitrogen fixation by Mimosa spp. in the Cerrado and Caatinga biomes of Brazil
- 2010
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In: New Phytologist. - : Wiley. - 0028-646X .- 1469-8137. ; 186:4, s. 934-946
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Journal article (peer-reviewed)abstract
- P>An extensive survey of nodulation in the legume genus Mimosa was undertaken in two major biomes in Brazil, the Cerrado and the Caatinga, in both of which there are high degrees of endemicity of the genus. Nodules were collected from 67 of the 70 Mimosa spp. found. Thirteen of the species were newly reported as nodulating. Nodules were examined by light and electron microscopy, and all except for M. gatesiae had a structure typical of effective Mimosa nodules. The endosymbiotic bacteria in nodules from all of the Mimosa spp. were identified as Burkholderia via immunolabelling with an antibody against Burkholderia phymatum STM815. Twenty of the 23 Mimosa nodules tested were shown to contain nitrogenase by immunolabelling with an antibody to the nitrogenase Fe- (nifH) protein, and using the delta 15N (15N natural abundance) technique, contributions by biological N-2 fixation of up to 60% of total plant N were calculated for Caatinga Mimosa spp. It is concluded that nodulation in Mimosa is a generic character, and that the preferred symbionts of Brazilian species are Burkholderia. This is the first study to demonstrate N-2 fixation by beta-rhizobial symbioses in the field.
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| 195. |
- Duong, Vicky, et al.
(author)
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Exploring translational gaps between basic scientists, clinical researchers, clinicians, and consumers : Proceedings and recommendations arising from the 2020 mine the gap online workshop
- 2021
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In: Osteoarthritis and Cartilage Open. - : Elsevier BV. - 2665-9131. ; 3:2
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Journal article (peer-reviewed)abstract
- Objective: To provide a summary of the translational gaps in musculoskeletal research as identified in the Mine the Gap workshop and propose possible solutions. Methods: The Mine the Gap online workshop was hosted on October 14th and 15th, 2020. Five international panels, each comprised of a clinician, clinical researcher and basic scientist, presented gaps and proposed solutions for the themes of biomechanics, pain, biological measurements, phenotypes and imaging. This was followed by an interactive panel discussion with consumer insights. Results: A number of translational gaps and proposed solutions across each of the five themes were identified. A consumer panel provided constructive feedback highlighting the need for improved resources, communication and shared decision making, and treatment individualisation. Conclusion: This brief report provides a greater understanding of the diverse work and gaps relevant to fundamental/discovery scientists, clinical researchers and clinicians working across the musculoskeletal field. The numerous translational gaps highlight the need to improve communication and collaboration across the musculoskeletal field.
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| 196. |
- Elliott, J. A., et al.
(author)
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Risk factors for loss of bone mineral density after curative esophagectomy
- 2019
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In: Archives of Osteoporosis. - : Springer Science and Business Media LLC. - 1862-3522 .- 1862-3514. ; 14:1
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Journal article (peer-reviewed)abstract
- .Summary Micronutrient and fat malabsorption and altered enteroendocrine signaling occur after esophagectomy for cancer; however, the impact of malnutrition on bone health in this cohort has not been previously investigated. In this study, the prevalence of osteoporosis increased after curative surgery, associated with disease-specific, treatment-related, and population risk factors.PurposeImproved oncologic outcomes in esophageal cancer (EC) have resulted in increased survivorship and a focus on long-term quality of life. Malnutrition and micronutrient malabsorption are common among patients with EC, but the effect on bone metabolism is not known. The aim of this study was to characterize changes in bone mineral density (BMD) following curative esophagectomy.MethodsConsecutive disease-free patients who underwent esophagectomy with gastric conduit for pathologically node-negative disease from 2000 to 2014 were included. BMD was assessed at vertebral levels T12-L5 by computed tomography using a simple trabecular region-of-interest attenuation technique, and serum markers of nutritional status and bone metabolism were examined. Independent risk factors for osteoporosis were identified by multivariable logistic regression.ResultsSeventy-five consecutive patients were studied. Osteoporosis was present in 25% at diagnosis. BMD declined at 1 and 2years postoperatively (144.345.8 versus 128.6 +/- 46.2 and 122.7 +/- 43.5 Hounsfield Units (HU), P<0.0001), with increased osteoporosis prevalence to 38% and 44% (P=0.049), respectively. No significant postoperative change in vitamin D, calcium, or phosphate was observed, but alkaline phosphatase increased significantly (P<0.001). While female sex (P=0.004) and ASA grade (P=0.043) were independently associated with osteoporosis at diagnosis, age (P=0.050), female sex (P=0.023), smoking (P=0.024), and pathologic T stage (P=0.023) were independently predictive of osteoporosis at 1year postoperatively.Conclusions p id=Par5 Osteoporosis is prevalent among disease-free patients post-esophagectomy for EC, associated with disease-specific, treatment-related, and population risk factors. Strategies which minimize BMD decline should be considered to avoid fragility fractures in this cohort.
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