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21.
Background
Dietary oleic acid may prevent pancreatic ductal adenocarcinoma (PDA) by reducing hyperinsulinaemia which can otherwise promote DNA damage and tumour growth. Results from previous epidemiological studies investigating oleic acid are inconsistent. This study aims to clarify the relationship between dietary oleic acid intake and the risk of developing PDA using nutritional information from food diaries plus published serum biomarker data from HbA1c.Methods
23,658 participants, aged 40–74 years, were recruited into EPIC-Norfolk and completed 7-day food diaries which recorded; foods, brands and portion sizes to calculate nutrient intakes. Serum HbA1c was measured at recruitment in 11,147 participants (48.7% of cohort). Hazard ratios (HRs) for quintiles of dietary oleic acid intake and serum HbA1c were estimated using Cox regression. Additional analyses were made according to whether body mass index (BMI) was greater or less than 25?kg/m2 as this influences hyperinsulinaemia.Results
88 participants (55% women) developed PDA after a mean follow-up of 8.4 years (SD?=?3.9) (mean age at diagnosis?=?72.6 years, SD?=?8.8). A decreased risk of PDA was associated with increased dietary oleic acid intake (highest vs lowest quintile, HR?=?0.29, 95% CI?=?0.10–0.81, P trend across quintiles?=?0.011), with statistical significance maintained when BMI>25?kg/m2 but not if BMI<25?kg/m2. An elevated serum HbA1c was associated with increased risk of disease (highest vs lowest quintiles, HR?=?6.32, 95% CI?=?1.38–28.89, P for trend?=?0.004).Conclusions
The data supports a protective role of oleic acid against development of PDA in those with higher BMIs possibly through influencing hyperinsulinaemia. Oleic acid intake should be accurately measured in future aetiological studies. 相似文献22.
23.
B Gencer TH Collet V Virgini DC Bauer J Gussekloo AR Cappola D Nanchen WP den Elzen P Balmer RN Luben M Iacoviello V Triggiani J Cornuz AB Newman KT Khaw JW Jukema RG Westendorp E Vittinghoff D Aujesky N Rodondi;for the Thyroid Studies Collaboration 《Circulation》2012,126(9):1040-1049
BACKGROUND: American College of Cardiology/American Heart Association guidelines for the diagnosis and management of heart failure recommend investigating exacerbating conditions such as thyroid dysfunction, but without specifying the impact of different thyroid-stimulation hormone (TSH) levels. Limited prospective data exist on the association between subclinical thyroid dysfunction and heart failure events. METHODS AND RESULTS: We performed a pooled analysis of individual participant data using all available prospective cohorts with thyroid function tests and subsequent follow-up of heart failure events. Individual data on 25 390 participants with 216 248 person-years of follow-up were supplied from 6 prospective cohorts in the United States and Europe. Euthyroidism was defined as TSH of 0.45 to 4.49 mIU/L, subclinical hypothyroidism as TSH of 4.5 to 19.9 mIU/L, and subclinical hyperthyroidism as TSH <0.45 mIU/L, the last two with normal free thyroxine levels. Among 25 390 participants, 2068 (8.1%) had subclinical hypothyroidism and 648 (2.6%) had subclinical hyperthyroidism. In age- and sex-adjusted analyses, risks of heart failure events were increased with both higher and lower TSH levels (P for quadratic pattern <0.01); the hazard ratio was 1.01 (95% confidence interval, 0.81-1.26) for TSH of 4.5 to 6.9 mIU/L, 1.65 (95% confidence interval, 0.84-3.23) for TSH of 7.0 to 9.9 mIU/L, 1.86 (95% confidence interval, 1.27-2.72) for TSH of 10.0 to 19.9 mIU/L (P for trend <0.01) and 1.31 (95% confidence interval, 0.88-1.95) for TSH of 0.10 to 0.44 mIU/L and 1.94 (95% confidence interval, 1.01-3.72) for TSH <0.10 mIU/L (P for trend=0.047). Risks remained similar after adjustment for cardiovascular risk factors. CONCLUSION: Risks of heart failure events were increased with both higher and lower TSH levels, particularly for TSH ≥10 and <0.10 mIU/L. 相似文献
24.
Collet TH Gussekloo J Bauer DC den Elzen WP Cappola AR Balmer P Iervasi G Åsvold BO Sgarbi JA Völzke H Gencer B Maciel RM Molinaro S Bremner A Luben RN Maisonneuve P Cornuz J Newman AB Khaw KT Westendorp RG Franklyn JA Vittinghoff E Walsh JP Rodondi N;Thyroid Studies Collaboration 《Archives of internal medicine》2012,172(10):799-809
25.
Mérino D Khaw SL Glaser SP Anderson DJ Belmont LD Wong C Yue P Robati M Phipson B Fairlie WD Lee EF Campbell KJ Vandenberg CJ Cory S Roberts AW Ludlam MJ Huang DC Bouillet P 《Blood》2012,119(24):5807-5816
The BH3-mimetic ABT-737 and an orally bioavailable compound of the same class, navitoclax (ABT-263), have shown promising antitumor efficacy in preclinical and early clinical studies. Although both drugs avidly bind Bcl-2, Bcl-x(L), and Bcl-w in vitro, we find that Bcl-2 is the critical target in vivo, suggesting that patients with tumors overexpressing Bcl-2 will probably benefit. In human non-Hodgkin lymphomas, high expression of Bcl-2 but not Bcl-x(L) predicted sensitivity to ABT-263. Moreover, we show that increasing Bcl-2 sensitized normal and transformed lymphoid cells to ABT-737 by elevating proapoptotic Bim. In striking contrast, increasing Bcl-x(L) or Bcl-w conferred robust resistance to ABT-737, despite also increasing Bim. Cell-based protein redistribution assays unexpectedly revealed that ABT-737 disrupts Bcl-2/Bim complexes more readily than Bcl-x(L)/Bim or Bcl-w/Bim complexes. These results have profound implications for how BH3-mimetics induce apoptosis and how the use of these compounds can be optimized for treating lymphoid malignancies. 相似文献
26.
27.
Anne-Katrin Hickmann Sönke Langner Michael Kirsch Jörg Baldauf Cornelia Müller Alexander Khaw Henry W. S. Schroeder 《Neurosurgical review》2013,36(2):267-278
Delayed cerebral ischemia remains a severe potential complication of aneurysmal subarachnoid hemorrhage (SAH) possibly leading to death and disability. We evaluated a semiquantitative and visual analysis of perfusion computed tomography (PCT) as a predictor of clinically relevant vasospasm (CRV) in patients with aneurysmal SAH. Thirty-eight patients with aneurysmal SAH were analyzed yielding 145 PCT scans. PCT, clinical examination, and transcranial Doppler ultrasound (TCD) were performed on days 3, 7, 10, and 14 after hemorrhage. Cerebral blood flow, cerebral blood volume, and time to peak (TTP) were analyzed semiquantitatively using six regions of interest, and visually for signs of cerebral hypoperfusion. CRV was defined as secondary cerebral infarction (CI) seen on cranial computed tomography scans and/or delayed neurological deterioration (DND). CI occurred in 13 (34.2 %) and DND in 11 patients (28.9 %). With TCD as pretest, TTP had a sensitivity of 90 % and a specificity of 72 % (cutoff value, 0.963) as predictor for CI. TTP’s sensitivity as predictor for DND was 90 % with a specificity of 61.1 % (cutoff value, 0.983). Visual analysis of TTP showed a negative predictive value of 100 % with a positive predictive value of 52 %. TTP is a sensitive and specific perfusion parameter in predicting CI in patients with SAH. Its use in the clinical setting may optimize the early treatment of patients at risk for vasospasm before the onset of clinical deterioration, especially when applying TCD as pretest. Further investigation in a larger patient population is required. 相似文献
28.
Clinical and patient‐reported outcomes of Chinese patients undergoing haemodialysis in hospital or in the community: A 1‐year longitudinal study
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29.
30.
Helena Johansson John A Kanis Anders Odén Eugene McCloskey Roland D Chapurlat Claus Christiansen Steve R Cummings Adolfo Diez‐Perez John A Eisman Saeko Fujiwara Claus‐C Glüer David Goltzman Didier Hans Kay‐Tee Khaw Marc‐Antoine Krieg Heikki Kröger Andrea Z LaCroix Edith Lau William D Leslie Dan Mellström L Joseph Melton III Terence W O'Neill Julie A Pasco Jerilynn C Prior David M Reid Fernando Rivadeneira Tjerd van Staa Noriko Yoshimura M Carola Zillikens 《Journal of bone and mineral research》2014,29(1):223-233
Several recent studies suggest that obesity may be a risk factor for fracture. The aim of this study was to investigate the association between body mass index (BMI) and future fracture risk at different skeletal sites. In prospective cohorts from more than 25 countries, baseline data on BMI were available in 398,610 women with an average age of 63 (range, 20–105) years and follow up of 2.2 million person‐years during which 30,280 osteoporotic fractures (6457 hip fractures) occurred. Femoral neck BMD was measured in 108,267 of these women. Obesity (BMI ≥ 30 kg/m2) was present in 22%. A majority of osteoporotic fractures (81%) and hip fractures (87%) arose in non‐obese women. Compared to a BMI of 25 kg/m2, the hazard ratio (HR) for osteoporotic fracture at a BMI of 35 kg/m2 was 0.87 (95% confidence interval [CI], 0.85–0.90). When adjusted for bone mineral density (BMD), however, the same comparison showed that the HR for osteoporotic fracture was increased (HR, 1.16; 95% CI, 1.09–1.23). Low BMI is a risk factor for hip and all osteoporotic fracture, but is a protective factor for lower leg fracture, whereas high BMI is a risk factor for upper arm (humerus and elbow) fracture. When adjusted for BMD, low BMI remained a risk factor for hip fracture but was protective for osteoporotic fracture, tibia and fibula fracture, distal forearm fracture, and upper arm fracture. When adjusted for BMD, high BMI remained a risk factor for upper arm fracture but was also a risk factor for all osteoporotic fractures. The association between BMI and fracture risk is complex, differs across skeletal sites, and is modified by the interaction between BMI and BMD. At a population level, high BMI remains a protective factor for most sites of fragility fracture. The contribution of increasing population rates of obesity to apparent decreases in fracture rates should be explored. © 2014 American Society for Bone and Mineral Research. 相似文献