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María A. Tapia-Laliena Nina Korzeniewski Markus Hohenfellner Stefan Duensing 《Urologic oncology》2014,32(8):1101-1107
ObjectivesIn this review, we will discuss the latest advances in our understanding of the relationship between the cellular DNA damage response and genomic instability in prostate cancer and the emerging possibilities to exploit these aberrations as prognostic biomarkers and guides for personalized patient management.MethodsImportant findings related to genomic instability in prostate cancer were retrieved from the literature and combined with our own results and a translational perspective.ResultsProstate cancer is characterized by a highly altered genomic landscape with a wide spectrum of genomic alterations, including somatic mutations, copy number alterations (CNAs), gene fusions, complex chromosomal rearrangements, and aneuploidy. In addition, massive DNA damaging events, including chromothripsis and chromoplexy, which can lead to extensive genomic insults in a single step, have been identified. A number of these genomic aberrations have been found to provide prognostic information and can therefore help to identify high-risk patients. In addition, defects in the DNA damage checkpoint and repair machinery can potentially be harnessed for therapeutic purposes.ConclusionsGenomic instability plays a crucial role in the malignant progression of prostate cancer and can be exploited for the development of novel prognostic biomarkers and innovative therapies. 相似文献
63.
背景 一般出租车司机受工作时间长、精神高度紧张、饮食不规律、静坐时间长等影响,慢性病患病率明显高于一般人群。相较于一般出租车司机的相关研究,国内外对于网约车司机慢性病等健康状况的相关研究目前尚未开展,网约车司机的健康状况也未引
起政府和行业的足够重视。因此,本研究从网约车司机的高血压患病状况入手,分析其健康影响因素,为改善网约车司机健康状况提出建议。目的 通过对网约车司机的高血压患病现状和影响因素的调查,为网约车司机的健康管理提出对策建议。方法 2017年9—11月,
通过问卷星制作电子表格,向全国网约车司机账号随机发放调查问卷,同一账号只能填写一次问卷。调查问卷内容包括人口学特征、社会经济学特征、工作特征、健康行为、高血压患病情况、健康意识与健康需求。结果 共回收问卷9 003份,有效问卷8 990份,回收有
效率为99.86%。8 990例研究对象中,高血压777例(8.64%)。多因素Logistic回归分析结果显示,年龄35~54岁〔OR=0.582,95%CI(0.408,0.829)〕和18~34岁〔OR=0.276,95%CI(0.188,0.407)〕,中部地区〔OR=1.523,95%CI(1.199,1.953)〕和东部地区〔OR=1.398,95%CI(1.140,1.716)〕,专职司机年数≥3年〔OR=1.218,95%CI(1.044,1.422)〕,开车时间段为白天和晚上、不固定〔OR=0.847,95%CI(0.718,0.999)〕,每天下车活动时长≥5 min〔OR=0.784,95%CI(0.670,0.917)〕,每天睡眠时长≥6 h〔OR=0.806,95%CI(0.681,0.954)〕,饮酒频率≥3 d/周〔OR=1.383,95%CI(1.112,1.719)〕、肥胖程度(过轻)〔OR=2.669,95%CI(1.799,3.961)〕和肥胖程度(肥胖)〔OR=3.153,95%CI(2.612,3.806)〕是网约车司机高血压患病的影响因素(P<0.05)。高血压组1年内做过健康体检比例、最近一次测血压时间为1个月内比例均高于非高血压组(P<0.05)。高血压组从手机、电视、广播处获取健康知识所占比例高于非高血压组,从互联网、其他方面获取健康知识所占比例低于非高血压组(P<0.05);高血压组获取风险预
防、症状诊断、治疗效果、医院专科的知识所占比例均高于非高血压组(P<0.05)。结论 需要加强对网约车司机的健康管理,尤其是年龄≥55岁、中东部地区、从事专职司机年数≥3年、白天或晚上开车时间段固定、没有下车活动习惯、每天睡眠时长<6 h、饮酒频率≥
3 d/周、健康程度为偏瘦和肥胖的网约车司机是高血压高风险人群。 相似文献
64.
Tone K. Omsland Nina Emaus Grethe S. Tell Luai A. Ahmed Jacqueline R. Center Nguyen D. Nguyen Clara G. Gjesdal Siri Forsmo Berit Schei Anne Johanne Søgaard Haakon E. Meyer 《BONE》2013,52(1):493-497
BackgroundSecond hip fracture risk is elevated after the first, however whether risk differs with age, by sex or over time is not well known.ObjectiveTo examine the risk of second hip fracture by sex, age and time after first hip fracture.DesignData on all hip fractures in subjects 50 years and older and treated in Norwegian hospitals during 1999–2008 were retrieved. Surgical procedure codes and additional diagnosis codes were used to define incident fractures. Survival analyses with and without adjustment for competing risk of death were used to estimate the risk of second hip fracture.ResultsAmong the 81,867 persons who sustained a first hip fracture, 6161 women and 1782 men suffered a second hip fracture during follow-up. The overall age-adjusted hazard ratio (HR) of a second hip fracture did not differ between the sexes (women versus men, HR = 1.03; 95% confidence interval (CI): 0.98–1.09). Taking competing risk of death into account, the corresponding age-adjusted HR of a second hip fracture was 1.40 (95% CI: 1.33–1.47) in women compared to men. The greater risk in women was due to a higher mortality in men. Based on competing risk analyses, we estimate that 15% of women and 11% of men will have suffered a second hip fracture within 10 years after the first hip fracture. The ten-year cumulative incidence was above 10% in all age-groups, except in men 90 years and older.ConclusionFracture preventive strategies have a large potential in both women and men who suffer their first hip fracture due to the high risk of another hip fracture. 相似文献
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Nina Tamminen Pia Solin Margaret M. Barry Lasse Kannas Eija Stengård Tarja Kettunen 《International Journal of Mental Health Promotion, The》2016,18(4):177-198
This study explored and clarified the nature and characteristics of the concept of mental health promotion. The study also investigated how these characteristics appear in current policies and strategies. A total of 30 scientific articles and policy documents were identified and analysed using Rodgers’s systematic evolutionary concept analysis method. The analysis provided valuable information on the attributes, related concepts, antecedents, consequences and references of mental health promotion, indicating that the concept is a distinct concept comprising a unique set of attributes and characteristics. A concept mapping of mental health promotion was subsequently developed. The analysis and the concept mapping provide health professionals, policy-makers and researchers with a framework, upon which well-grounded mental health promotion practice and evaluation research can be based. 相似文献
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69.
Christian Pehm?ller Nina Brandt Jesper B. Birk Louise D. H?eg Kim A. Sj?berg Laurie J. Goodyear Bente Kiens Erik A. Richter J?rgen F.P. Wojtaszewski 《Diabetes》2012,61(11):2743-2752
Excess lipid availability causes insulin resistance. We examined the effect of acute exercise on lipid-induced insulin resistance and TBC1 domain family member 1/4 (TBCD1/4)-related signaling in skeletal muscle. In eight healthy young male subjects, 1 h of one-legged knee-extensor exercise was followed by 7 h of saline or intralipid infusion. During the last 2 h, a hyperinsulinemic-euglycemic clamp was performed. Femoral catheterization and analysis of biopsy specimens enabled measurements of leg substrate balance and muscle signaling. Each subject underwent two experimental trials, differing only by saline or intralipid infusion. Glucose infusion rate and leg glucose uptake was decreased by intralipid. Insulin-stimulated glucose uptake was higher in the prior exercised leg in the saline and the lipid trials. In the lipid trial, prior exercise normalized insulin-stimulated glucose uptake to the level observed in the resting control leg in the saline trial. Insulin increased phosphorylation of TBC1D1/4. Whereas prior exercise enhanced TBC1D4 phosphorylation on all investigated sites compared with the rested leg, intralipid impaired TBC1D4 S341 phosphorylation compared with the control trial. Intralipid enhanced pyruvate dehydrogenase (PDH) phosphorylation and lactate release. Prior exercise led to higher PDH phosphorylation and activation of glycogen synthase compared with resting control. In conclusion, lipid-induced insulin resistance in skeletal muscle was associated with impaired TBC1D4 S341 and elevated PDH phosphorylation. The prophylactic effect of exercise on lipid-induced insulin resistance may involve augmented TBC1D4 signaling and glycogen synthase activation.Studies in human and rodent models have revealed deleterious effects of excess lipid availability on peripheral insulin sensitivity (1,2). Intracellular increases in fatty acid metabolites, such as diacylglycerol (DAG) and ceramide, may play critical roles in mediating lipid-induced insulin resistance by inducing serine phosphorylation of insulin-receptor substrate 1 (IRS-1) (3–6) and consequently inhibiting downstream signaling to GLUT4 translocation. However, recent reports challenge such causality. These studies revealed unaltered signal transduction at the level of IRS-1, IRS-1–associated phosphatidylinositol-3-kinase (PI3K) activity, Akt, and TBC1 domain family member 4 (TBC1D4) phosphorylation (phospho-Akt-substrate [PAS] an unspecific antibody recognizing phosphorylated Akt substrate motifs), after 2–7 h of lipid infusion (7–11). When DAG and/or ceramide levels were reported, no changes in skeletal muscle DAG or ceramide levels were found after lipid infusion (7,11).We recently showed that lactate release in human skeletal muscle is augmented along with reduced respiratory exchange ratio (RER) values during lipid infusion (11). This could indicate suppressed activity of the pyruvate dehydrogenase (PDH) complex, which in turn could lead to a reduction in glucose uptake according to the Randle cycle (12). Here, we wished to investigate whether this increase in leg lactate release and reduced RER values were accompanied by altered regulation of PDH, measured by site-specific phosphorylation.Exercise increases peripheral insulin sensitivity (13–15). After an acute bout of exercise, the ability for insulin to stimulate glucose uptake in skeletal muscle is increased several hours into recovery (14,16). This effect can be ascribed to adaptations in the exercised muscle rather than changes in systemic factors (13,17,18) and is observed in both healthy and insulin-resistant states (e.g., obesity) (19) and type 2 diabetes (20). A recent study has shown that a single bout of exercise can prevent subsequent lipid-induced impairments in whole-body glucose tolerance assessed by an intravenous glucose tolerance test (IVGTT) (2). It was hypothesized that repartitioning fatty acids toward intramuscular triacylglycerol (IMTG) synthesis and storage rather than DAG or ceramide might be a primary mediator of the beneficial effects of exercise on lipid-induced impairments in glucose tolerance (2). Enhanced insulin sensitivity after a bout of exercise is associated with increased GLUT4 recruitment to the plasma membrane (21) and not with altered protein synthesis (e.g., GLUT4 protein) (22), but has not been associated with altered signal transduction through the insulin receptor, IRS-1, PI3K, or Akt (13,22,23). Recently, the hypothesis was put forward (24) that the guanosine triphosphatase (GTPase) activating proteins TBC1 domain family member 1 (TBC1D1) and 4 (TBC1D4) might serve as points of convergence for insulin dependent and independent signaling pathways to GLUT4 translocation. In agreement with this hypothesis, PAS phosphorylation of TBC1D4 is elevated along with insulin-stimulated glucose uptake for up to 27 h after exercise in skeletal muscle of rats (25), and we recently showed that phosphorylation of TBC1D4 on specific residues was elevated 4 h after a single bout of exercise in human skeletal muscle (26).TBC1D4/D1 are multikinase substrates proposed to be involved in contraction- and insulin-stimulated glucose uptake in mice (27,28), and exercise and insulin both substantially increase TBC1D4/D1 phosphorylation in human skeletal muscle (29,30). TBC1D4/D1 contain several phosphorylation sites distinctly phosphorylated by various kinases, including Akt and 5′AMP-activated protein kinase (AMPK) (28,31–33). Phosphorylation of TBC1D4/D1 and subsequent 14-3-3 binding is proposed to lead to inactivation of the GTPase-activating proteins, decreasing their inhibitory function on the GLUT4 translocation process and thus, potentially, increasing the GLUT4 capacity of the surface membrane.In the current study we tested the hypothesis that prior exercise prevents subsequent lipid-induced insulin resistance in human skeletal muscle through regulation of the signaling molecules TBC1D4/TBC1D1. 相似文献
70.
S Waterloo T Nguyen LA Ahmed JR Center B Morseth ND Nguyen JA Eisman AJ Søgaard N Emaus 《BMC musculoskeletal disorders》2012,13(1):163
ABSTRACT: BACKGROUND: Vertebral fractures, the most common type of osteoporotic fractures, are associated with increased risk of subsequent fracture, morbidity, and mortality. The aim of this study was to examine the contribution of important risk factors to the variability in vertebral fracture risk. METHODS: Vertebral fracture was ascertained by VFA method (DXA, GE Lunar Prodigy) in 2887 men and women, aged between 38 and 87 years, in the population-based Tromso Study 2007/2008. Bone mineral density (BMD; g/cm2) at the hip was measured by DXA. Lifestyle information was collected by questionnaires. Multivariable logistic regression model, with anthropometric and lifestyle factors included, was used to assess the association between each or combined risk factors and vertebral fracture risk. Population attributable risk was estimated for combined risk factors in the final multivariable model. RESULTS: In both sexes, age (odds ratio [OR] per 5 year increase: 1.32; 95% CI 1.19-1.45 in women and 1.21; 95% CI 1.10-1.33 in men) and BMD (OR per SD decrease: 1.60; 95% CI 1.34-1.90 in women and1.40; 95% CI 1.18-1.67 in men) were independent risk factors for vertebral fracture. At BMD levels higher than 0.85 g/cm2, men had a greater risk of fracture than women (OR 1.52; 95% CI 1.14-2.04), after adjusting for age. In women and men, respectively, approximately 46% and 33% of vertebral fracture risk was attributable to advancing age (more than 70 years) and low BMD (less than 0.85 g/cm2), with the latter having a greater effect than the former. CONCLUSIONS: These data confirm that age and BMD are major risk factors for vertebral fracture risk. However, in both sexes the two factors accounted for less than half of fracture risk. The identification of individuals with vertebral fracture is still a challenge. 相似文献