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1.
Sci Rep ; 9(1): 13407, 2019 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-31527690

RESUMO

Dyslipidemia and statin use have been associated with colorectal cancer (CRC), but prospective studies have shown mixed results. We aimed to determine whether dyslipidemia is causally linked to CRC risk using a Mendelian randomization approach and to explore the association of statins with CRC. A case-control study was performed including 1336 CRC cases and 2744 controls (MCC-Spain). Subjects were administered an epidemiological questionnaire and were genotyped with an array which included polymorphisms associated with blood lipids levels, selected to avoid pleiotropy. Four genetic lipid scores specific for triglycerides (TG), high density lipoprotein cholesterol (HDL), low density lipoprotein cholesterol (LDL), or total cholesterol (TC) were created as the count of risk alleles. The genetic lipid scores were not associated with CRC. The ORs per 10 risk alleles, were for TG 0.91 (95%CI: 0.72-1.16, p = 0.44), for HDL 1.14 (95%CI: 0.95-1.37, p = 0.16), for LDL 0.97 (95%CI: 0.81-1.16, p = 0.73), and for TC 0.98 (95%CI: 0.84-1.17, p = 0.88). The LDL and TC genetic risk scores were associated with statin use, but not the HDL or TG. Statin use, overall, was a non-significant protective factor for CRC (OR 0.84; 95%CI: 0.70-1.01, p = 0.060), but lipophilic statins were associated with a CRC risk reduction (OR 0.78; 95%CI 0.66-0.96, p = 0.018). Using the Mendelian randomization approach, our study does not support the hypothesis that lipid levels are associated with the risk of CRC. This study does not rule out, however, a possible protective effect of statins in CRC by a mechanism unrelated to lipid levels.

2.
Breast Cancer Res Treat ; 177(3): 749-760, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31317349

RESUMO

PURPOSE: Literature on the separate effects of physical activities (PA) on risk of breast cancer (BC) sub-types is heterogeneous. We investigated domain-specific associations between PA and BC risk by menopausal status and molecular subtype. METHODS: 1389 histologically confirmed invasive BC cases and 1712 controls from the MCC-Spain study were included (age: 20-85 years). Questionnaire information on PA at work, at home, and during leisure time, including recreational PA and sedentary time, and data on reproductive history, anthropometry, family history of BC, diet, and lifestyles were obtained through face-to-face interviews. Information on the expression of oestrogen (ER), progesterone (PR), and HER2 receptors was available for > 95% of the cases. Mixed-effects multivariable logistic regression models were used to estimate odds ratios (OR) of BC sub-types. RESULTS: Occupational PA (OPA) intensity was associated with higher BC risk. Associations were stronger for pre-menopausal (ORactive/very active vs. sedentary job 1.89; 95% confidence interval (CI) 1.22, 2.91) and ER+/PR+, HER2- tumours (OR 1.80; 95% CI 1.28, 2.53). Sedentary time was associated with higher risk of post-menopausal BC (OR6-9 vs. <3 h/day 1.69; 95% CI 1.22, 2.32). Moderate-to-high-intensity household (HPA) and recreational PA (RPA) were inversely associated with BC occurrence in pre- and post-menopausal women, with estimated 14-33% lower risks (P for trend < 0.001) above 1000 MET·min/week. CONCLUSIONS: Higher levels of HPA and RPA were associated with lower risk of BC, with heterogeneity by molecular type, whereas sitting time was a consistent independent risk factor of BC risk. The positive association found for OPA with ER+/PR+ BC deserves further investigation.

3.
Nano Lett ; 19(7): 4490-4497, 2019 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-31188620

RESUMO

Taper-free InP twinning superlattice (TSL) nanowires with an average twin spacing of ∼13 nm were grown along the zinc-blende close-packed [111] direction using metalorganic vapor phase epitaxy. The mechanical properties and fracture mechanisms of individual InP TSL nanowires in tension were ascertained by means of in situ uniaxial tensile tests in a transmission electron microscope. The elastic modulus, failure strain, and tensile strength along the [111] direction were determined. No evidence of inelastic deformation mechanisms was found before fracture, which took place in a brittle manner along the twin boundary. The experimental results were supported by molecular dynamics simulations of the tensile deformation of the nanowires that also showed that the fracture of twinned nanowires occurred in the absence of inelastic deformation mechanisms by the propagation of a crack from the nanowire surface along the twin boundary.

5.
Eur J Nutr ; 2019 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-31069457

RESUMO

PURPOSE: To evaluate the association between dietary fat and fat subtype and breast cancer development. METHODS: We conducted a case-control study with 1181 cases of incident breast cancer, diagnosed between 2007 and 2012, and 1682 population controls frequency matched (by age, sex, and region) from the Spanish multicenter case-control study MCC-Spain. RESULTS: We found a significant protective effect in premenopausal women of total fat intake [OR 0.51 95% CI (0.31-0.86) highest versus lowest tertile], but no effect was observed in menopausal women [OR 1.15 95% CI (0.83-1.60)]. Analyzing by type of fat, this protective effect persisted only for the monounsaturated fatty acids [OR 0.51 95% CI (0.32-0.82)]. In contrast, other fatty acids did not have a significant effect. In addition, a protection against risk of breast cancer was found when polyunsaturated fats were "substituted" by monounsaturated, maintaining the same total fat intake [OR 0.68 95% CI (0.47-0.99)]. Finally, analyzing by breast cancer subtype, we found no effect, except in premenopausal women where intake of moderate [OR 0.52 95% CI (0.33-0.82)] and high monounsaturated fatty acids [OR 0.47 95% CI (0.27-0.82)] maintains a protective effect against ER/PR + tumors. In contrast, in menopausal women, a high intake of monounsaturated fatty acids was associated with higher risk of HER2 + tumors [OR 2.00 95% CI (0.97-4.13)]. CONCLUSION: Our study shows a differential effect of monounsaturated fatty acids according to menopausal status and breast cancer subtype.

6.
Artigo em Inglês | MEDLINE | ID: mdl-31033231

RESUMO

OBJECTIVE: To evaluate the impact of comorbidities on the physical function in patients with ankylosing spondylitis (AS) and psoriatic arthritis (PsA). METHODS: Cross-sectional analysis of the baseline visit from the CARMA study. Multivariate models with physical function as the dependent variable (BASFI and HAQ for AS and PsA, respectively) were performed. INDEPENDENT VARIABLES: A proxy for the Charlson Comorbidity Index (CCIp) (range: 0-27); sociodemographic data; disease activity (ESR and BASDAI in AS; DAS28-ESR in PsA); disease duration; radiographic damage and treatments. Results were reported as ß-coefficients, 95% confidence intervals [95%CI] and p-values. RESULTS: We included 738 patients with AS and 721 with PsA; 21% of them had more than one comorbidity. Comorbidity burden (CCIp) was independently associated with worse adjusted physical function in patients with PsA (ß: 0.11). Also, female sex (ß: 0.14), disease duration (ß: 0.01), disease activity (DAS28-ESR, ß: 0.19), NSAIDs (ß: 0.09), glucocorticoids (ß: 0.11) and biologics (ß: 0.15) were associated with worse function in patients with PsA. A higher educational level was associated with less disability (ß: -0.14). In patients with AS, age (ß: 0.03), disease activity (BASDAI; ß: 0.81), radiographic damage (ß: 0.61) and the use of biologics (ß: 0.51) were independently associated with worse function on multivariate analyses, but CCIp was not. CONCLUSION: The presence of comorbidities in patients with PsA is independently associated with worse physical function. The detection and control of the comorbidities may yield an integral management of the disease. This article is protected by copyright. All rights reserved.

7.
Sci Rep ; 9(1): 4264, 2019 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-30862942

RESUMO

Osteoporosis is a major health problem in terms of fracture probability and disability. The aim of this ecological study is to identify the temporal trends in osteoporosis mortality in Spain from 1999 to 2015. Data on the Spanish population and number of deaths due to osteoporosis were obtained from the Spanish National Institute for Statistics. Age-adjusted mortality rates were estimated. Join point regression was used to identify the years when changes in mortality s and annual percentage change in mortality rates took place. Women presented a greater mortality rate decrease (p < 0.001), though this mortality difference by sex was reduced by half at the end of the period. The higher the age, the faster the mortality rate declined in women, while no clear pattern could be identified in men. In women, significant changes in trends were identified in three age groups (50-54, 60-64 and 80-84 years old). A sustained decrease in osteoporosis-associated mortality was found in women aged 75-79 and ≥85 years and men aged 60-64. In conclusion, mortality caused by osteoporosis in Spain is decreasing faster in the older age ranges especially in women.

8.
Clin Exp Rheumatol ; 37(5): 774-782, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30789151

RESUMO

OBJECTIVES: Cardiovascular (CV) disease is one of the main causes of morbi-mortality in spondyloarthritis (SpA), partially explained by traditional CV risk factors. Information on lipoprotein(a) [Lp(a)], a non-conventional risk factor, in SpA is scarce. In this study we assessed the prevalence of hyperlipoproteinaemia(a) in SpA patients and analysed the possible related factors. METHODS: A baseline analysis was made of ankylosing spondylitis (AS) and psoriatic arthritis (PsA) patients and controls included in the CARMA project (CARdiovascular in RheuMAtology), a 10-year prospective study evaluating the risk of CV events in chronic inflammatory rheumatic diseases. A multivariate logistic regression model was performed using hyperlipoproteinaemia(a) (Lp(a) >50 mg/dl) as a dependent variable and adjusting for confounding factors. RESULTS: 19.2% (95% CI: 16.80-22.05) of the SpA patients [20.7% (95% CI: 16.91-24.82) of those with AS and 17.7% (95% CI: 14.15-21.75) of those with PsA] and 16.7% (95% CI: 13.23-20.86) of the controls had hyperlipoproteinaemia(a) (p=0.326). Adjusting for age and sex, SpA patients were more likely to have hyperlipoproteinaemia(a) than controls (OR: 1.43, 95%CI: 1.00-2.04; p=0.05), especially those with AS (OR: 1.81, 95%CI: 1.18-2.77; p=0.007). In the adjusted model, apolipoprotein B in all patients, non-steroidal anti-inflammatory drugs in AS, and female sex in PsA, were associated with hyperlipoproteinaemia(a). No disease-specific factors associated with hyperlipoproteinaemia(a) were identified. CONCLUSIONS: SpA patients show a moderately increased risk of hyperlipoproteinaemia(a) compared to controls, especially those with AS. Lp(a) determination may be of interest to improve the CV risk assessment in SpA patients.


Assuntos
Hiperlipoproteinemias , Espondilartrite , Artrite Psoriásica , Estudos de Casos e Controles , Comorbidade , Feminino , Humanos , Hiperlipoproteinemias/epidemiologia , Masculino , Estudos Prospectivos , Fatores de Risco , Espondilartrite/sangue , Espondilartrite/epidemiologia
9.
J Rheumatol ; 46(5): 483-491, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30647175

RESUMO

OBJECTIVE: Composite scores of cardiovascular (CV) risk factors underestimate the CV risk in patients with systemic lupus erythematosus (SLE). Carotid artery ultrasound (US) was found useful in identifying high CV-risk patients with inflammatory arthritis. We assessed the effect of carotid US assessments on the CV risk stratification of patients with SLE. METHODS: This cross-sectional study included 276 patients with SLE. These indices were measured: lipid profile, Systematic COronary Risk Evaluation (SCORE) risk calculation, and disease activity (SLE Disease Activity Index), severity (Katz), and damage [Systemic Lupus International Collaborating Clinics (SLICC)/American College of Rheumatology Damage Index]. Carotid plaques were assessed by US. A multivariable regression analysis, adjusted for classic CV-related factors, was performed to evaluate how risk reclassification was influenced by disease characteristics in patients with SLE. RESULTS: Thirty-six percent of patients had carotid plaques. However, only 6% of them fulfilled the definitions for high or very high risk according to the SCORE risk charts. Following carotid US assessment, 32% of the patients were reclassified as very high risk. Disease duration (OR 1.04, 95% CI 1.00-1.07, p = 0.025) and a SLICC > 0 (OR 2.48 95% CI 1.15-5.34, p = 0.020) were independently associated with a higher risk of reclassification. A predictive model for reclassification included age (cutoff 52 yrs, sensitivity 60%, specificity 86%), disease duration (cutoff 24 yrs, sensitivity 40%, specificity 82%), presence of hypertension, SLICC > 0, waist circumference (cutoff 102 cm, sensitivity 48%, specificity 84%), and C3 (cutoff 127 mg/dl, sensitivity 52%, specificity 92%) and triglyceride (cutoff 140 mg/dl, sensitivity 68%, specificity 79%) serum levels. CONCLUSION: Reclassification into a very high-risk category is frequent after carotid US assessments in patients with SLE. This is independently influenced by disease damage.

10.
Clin Exp Rheumatol ; 37(5): 731-739, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30620291

RESUMO

OBJECTIVES: To determine the incidence and risk factors of first cardiovascular event (CVE) in patients with chronic inflammatory rheumatic diseases (CIRD). METHODS: Analysis of data after 2.5 years of follow-up from the prospective study CARMA project, that includes patients with CIRD [rheumatoid arthritis (RA), ankylosing spondylitis (AS), and psoriatic arthritis (PsA)] and matched individuals without CIRD from 67 hospitals in Spain. CVE cumulative incidence per 1000 patients was calculated after 2.5 years from the start of the project. Weibull proportional hazard model was used to calculate hazard ratio (HR) and 95% confidence interval (95% CI) of the risk factors. RESULTS: 2595 (89.1%) patients completed the 2.5 years of follow-up visit. Cumulative incidence of CVE in patients with CIRD was 15.30 cases per 1000 patients (95% CI: 12.93-17.67), being higher in the subgroup with AS; 22.03 (95% CI: 11.01-33.04). Patients with AS (HR: 4.11; 95% CI: 1.07-15.79), those with older age (HR: 1.09; 95% CI: 1.05-1.13), systolic hypertension (HR: 1.02; 95% CI: 1.00-1.04) and long duration of the disease (HR: 1.07; 95% CI: 1.03-1.12) were at higher risk of first CVE during the 2.5 years of follow-up. In contrast, female gender was a protective factor (HR: 0.43; 95% CI: 0.18-1.00). CONCLUSIONS: Among CIRD patients prospectively followed-up at rheumatology outpatient clinics, those with AS show higher risk of first CVE. Besides cardiovascular risk factors, such as hypertension, being a man and older as well as having a long disease duration increase the risk of CVE in patients with CIRD.


Assuntos
Artrite Psoriásica/epidemiologia , Artrite Reumatoide/epidemiologia , Doenças Cardiovasculares/epidemiologia , Espondilite Anquilosante/epidemiologia , Idoso , Comorbidade , Feminino , Humanos , Incidência , Masculino , Estudos Prospectivos , Doenças Reumáticas/epidemiologia , Fatores de Risco , Espanha/epidemiologia
11.
Nutrients ; 11(1)2018 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-30577563

RESUMO

Zinc is a key trace element in normal prostate cell metabolism, and is decreased in neoplastic cells. However, the association between dietary zinc and prostate cancer (PC) in epidemiologic studies is a conflicting one. Our aim was to explore this association in an MCC-Spain case-control study, considering tumor aggressiveness and extension, as well as genetic susceptibility to PC. 733 incident cases and 1228 population-based controls were included for this study. Dietary zinc was assessed using a food frequency questionnaire, and genetic susceptibility was assessed with a single nucleotide polymorphisms (SNP)-based polygenic risk score (PRS). The association between zinc intake and PC was evaluated with mixed logistic and multinomial regression models. They showed an increased risk of PC in those with higher intake of zinc (Odds Ratio (OR) tertile 3vs1: 1.39; 95% Confidence interval (CI):1.00⁻1.95). This association was mainly observed in low grade PC (Gleason = 6 RRR tertile 3vs1: 1.76; 95% CI:1.18⁻2.63) as well as in localized tumors (cT1-cT2a RRR tertile 3vs1: 1.40; 95% CI:1.00⁻1.95) and among those with higher PRS (OR tertile 3vs1: 1.50; 95% CI:0.89⁻2.53). In conclusion, a higher dietary zinc intake could increase the risk of low grade and localized tumors. Men with higher genetic susceptibility0020might also have a higher risk of PC associated with this nutrient intake.


Assuntos
Dieta/efeitos adversos , Neoplasias da Próstata/etiologia , Zinco/efeitos adversos , Idoso , Estudos de Casos e Controles , Inquéritos sobre Dietas , Ingestão de Energia , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Neoplasias da Próstata/epidemiologia , Fatores de Risco , Espanha/epidemiologia , Zinco/análise
12.
Clin Exp Rheumatol ; 2018 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-30418124

RESUMO

OBJECTIVES: In patients with rheumatoid arthritis (RA), insulin resistance (IR), a component of the metabolic syndrome, is closely linked to the systemic inflammation induced by proinflammatory cytokines such as tumor necrosis factor-α and interleukin (IL)-6. In the present study, we aimed to assess if an intravenous administration of the anti-IL-6 receptor tocilizumab may yield a rapid improvement of IR in RA. METHODS: 50 consecutive non-diabetic patients with RA refractory to methotrexate, undergoing periodic treatment with tocilizumab, were studied. Besides disease activity, serum insulin, insulin/glucose ratio, insulin resistance (HOMA-IR) and insulin sensitivity (QUICKI) indexes were assessed immediately before and 1 hour after the end of an intravenous administration of tocilizumab (given in saline solution over 60 minutes). RESULTS: When comparing baseline data (immediately before) and 1 hour after finishing tocilizumab administration, we observed a dramatic decrease of the serum insulin levels and insulin/glucose ratio. Also, a statistically significant reduction of IR (HOMA-IR: mean± standard deviation immediately before: 2.62±2.03 vs. 1.65±1.15 1 hour after the end of the infusion (p<0.01) and a statistically significant increase of insulin sensitivity (QUICKI immediately before 0.34±0.03 vs. 0.37±0.04 1 hour after the end of tocilizumab infusion (p<0.01) was observed. CONCLUSIONS: The intravenous administration of tocilizumab yields a rapid beneficial effect on IR and insulin sensitivity in non-diabetic RA patients. These findings support the potential beneficial effect of the IL-6 blockade on the mechanisms associated with the development of metabolic syndrome and cardiovascular disease in patients with RA.

13.
J Rheumatol ; 2018 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-30275261

RESUMO

OBJECTIVE: In nondiabetic healthy individuals, insulin secretion and sensitivity are linked by a negative feedback loop characterized by a hyperbolic function. We aimed to study the association of traditional insulin resistance (IR) factors with insulin secretion and sensitivity, and to determine whether the hyperbolic equilibrium of this relation is preserved in patients with rheumatoid arthritis (RA). METHODS: This was a cross-sectional study encompassing 361 nondiabetic individuals: 151 with RA and 210 controls. Insulin, C-peptide, and IR indices by homeostatic model (HOMA2) were assessed. A multivariable analysis was performed to evaluate the differences in the correlation of traditional IR-related factors with glucose homeostasis molecules, as well as IR indices between patients and controls. Nonlinear regression analysis was used to assess the hyperbolic relation of insulin sensitivity and secretion. RESULTS: HOMA2-IR indices were higher in patients with RA than controls. Hepatic insulin extraction, as assessed by the insulin:C-peptide molar ratio, was lower in patients with RA after multivariable analysis (0.08 ± 0.02 vs 0.14 ± 0.07, p < 0.001). Traditional IR-related factors showed significantly lower adjusted correlation coefficients with IR indices in patients with RA. The association between insulin sensitivity and secretion showed a different hyperbolic relation in patients with RA: the variability explained by the curve was lower in RA (nonlinear r2 = 0.845 vs r2 = 0.928, p = 0.001) and ß coefficients (-0.74, 95% CI -0.77 to -0.70 vs -1.09, 95% CI -1.17 to -1.02, ng/ml, p < 0.001) were different in RA. CONCLUSION: The traditional factors associated with IR in healthy individuals are less related to IR in patients with RA. Insulin sensitivity and secretion yield a different hyperbolic equilibrium in RA.

14.
Arthritis Rheumatol ; 2018 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-30251476

RESUMO

OBJECTIVE: A genome-wide association study (GWAS) was conducted to shed light into the genetic background influencing the development of cardiovascular (CV) disease in patients diagnosed with rheumatoid arthritis (RA). METHODS: After quality control and imputation, a total of 6,308,944 polymorphisms across the whole genome were analysed in 2,989 RA patients from European origin. Data on subclinical atherosclerosis, obtained by carotid ultrasonography through assessment of carotid intima-media thickness (cIMT) and presence/absence of carotid plaques, were available for 1,355 individuals. RESULTS: A genetic variant of the RARB gene (rs116199914) was associated with cIMT values at the genome-wide level of significance (minor allele (G): beta (ß) coefficient=0.142, P=1.86E-08). Interestingly, rs116199914 overlapped with regulatory elements in tissues related to CV pathophysiology and immune cells. In addition, biological pathway enrichment and predictive protein-protein relationship analyses, including suggestive GWAS signals of potential relevance, revealed a functional enrichment of the collagen biosynthesis network related to the presence/absence of carotid plaques (GO:0032964, PFDR =4.01E-03). Furthermore, our data suggest a potential influence of the previously described candidate CV risk loci NFKB1, MSRA and ZC3HC1 (P=8.12E-04, P=5.94E-04 and P=2.46E-04, respectively). CONCLUSION: Our study strongly suggests that genetic variation within RARB contributes to the development of subclinical atherosclerosis in patients with RA. This article is protected by copyright. All rights reserved.

15.
Environ Int ; 121(Pt 1): 428-434, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30266013

RESUMO

OBJECTIVES: To explore the association of colorectal cancer with environmental solar radiation and sun exposure behavior, considering phenotypic variables (eye color, hair color and skin phenotype), dietary intake of vitamin D and calcium, and socio-demographic factors. STUDY DESIGN: Multicenter population-based frequency matched case-control study in Spain (MCC-Spain), with 2140 CRC cases and 3950 controls. METHODS: Data were obtained through personal interviews using a structured epidemiological questionnaire that included socio-demographic data, residential history, environmental exposures, behavior, phenotypic and dietary information. An environmental-lifetime sun exposure score was constructed combining residential history and average daily solar radiation, direct and diffuse. Logistic regression was used to explore the association between different variables. A structural equation model was used to verify the associations of the conceptual model. RESULTS: We found a lower risk of CRC in subjects frequently exposed to sunlight during the previous summer and skin burning due to sun exposure. No association was observed in relation to the residential solar radiation scores. Subjects with light eye or light hair colors had a lower risk of CRC that those with darker colors. Dietary calcium and vitamin D were also protective factors, but not in the multivariate model. The structural equation model analysis suggested that higher sun exposure was associated with a decreased risk of CRC, as well as dietary intake of calcium and vitamin D, and these factors are correlated among themselves and with environmental solar radiation and skin phenotypes. CONCLUSION: The results agree with previous observations that sun exposure, dietary vitamin D and calcium intake, and serum 25(OH)D concentration reduce the risk of CRC and indicate that these factors may be relevant for cancer prevention.

16.
Sci Rep ; 8(1): 13728, 2018 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-30213986

RESUMO

Calprotectin (CPT) is released during inflammation, also in the context of atherosclerosis. The link between CPT and the atherosclerotic process was evaluated in several diseases. However, studies in axial spondyloarthritis (axSpA), associated with a high incidence of subclinical atherosclerosis, are scarce. Therefore, we assessed the association of CPT with subclinical atherosclerosis and metabolic risk factors in axSpA. CPT serum levels were measured by enzyme-linked immunosorbent assay in 163 axSpA patients and 63 controls. Subclinical atherosclerosis was determined in patients by carotid ultrasonography (assessing the presence/absence of carotid plaques and carotid intima-media thickness [cIMT]). Data on inflammation, disease activity, lipid profile and treatment were collected to evaluate its relationship with CPT. axSpA patients evidenced lower CPT levels than controls. CPT showed no association with plaques or cIMT in axSpA. CPT and HDL-cholesterol negatively correlated, while a positive association of CPT with the atherogenic index was disclosed. Additionally, axSpA patients with C-reactive protein values at diagnosis higher than 3 mg/L displayed higher CPT levels. Our study shows no relationship between CPT and markers of subclinical atherosclerosis in axSpA. Nevertheless, it demonstrates an association of CPT with adverse lipid profiles and inflammatory biomarkers, which could further influence on the development of atherosclerosis.

17.
BMC Public Health ; 18(1): 1134, 2018 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-30241493

RESUMO

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used despite their risk of gastrointestinal bleeding or cardiovascular events. We report the profile of people taking NSAIDs in Spain, and we include demographic factors, health-related behaviours and cardiovascular disease history. METHODS: Four thousand sixtyparticipants were selected using a pseudorandom number list from Family Practice lists in 12 Spanish provinces. They completed a face-to-face computerized interview on their NSAID consumption, demographic characteristics, body mass index, alcohol and tobacco consumption and medical history. In addition, participants completed a self-administered food-frequency and alcohol consumption questionnaire. Factors associated with ever and current NSAID consumption were identified by logistic regression. RESULTS: Women consumed more non-aspirin NSAIDs (38.8% [36.7-41.0]) than men (22.3 [20.5-24.2]), but men consumed more aspirin (11.7% [10.3-13.2]) than women (5.2% [4.3-6.3]). Consumption of non-aspirin NSAIDs decrease with age from 44.2% (39.4-49.1) in younger than 45 to 21.1% (18.3-24.2) in older than 75, but the age-pattern for aspirin usage was the opposite. Aspirin was reported by about 11% patients, as being twice as used in men (11.7%) than in women (5.2%); its consumption increased with age from 1.7% (< 45 years old) to 12.4% (≥75 years old). Aspirin was strongly associated with the presence of cardiovascular risk factors or established cardiovascular disease, reaching odds ratios of 15.2 (7.4-31.2) in women with acute coronary syndrome, 13.3 (6.2-28.3) in women with strokes and 11.1 (7.8-15.9) in men with acute coronary syndrome. Participants with cardiovascular risk factors or diseases consumed as much non-aspirin NSAID as participants without such conditions. CONCLUSIONS: Non-aspirin NSAIDs were more consumed by women and aspirin by men. The age patterns of aspirin and non-aspirin NSAIDs were opposite: the higher the age, the lower the non-aspirin NSAIDs usage and the higher the aspirin consumption. People with cardiovascular risk factors or diseases consumed more aspirin, but they did not decrease their non-aspirin NSAIDs usage.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Aspirina/uso terapêutico , Adulto , Distribuição por Idade , Idoso , Doenças Cardiovasculares/epidemiologia , Estudos de Casos e Controles , Feminino , Hemorragia Gastrointestinal , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Distribuição por Sexo , Espanha/epidemiologia , Inquéritos e Questionários
18.
PLoS One ; 13(8): e0201750, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30106959

RESUMO

INTRODUCTION: Phototype has been associated with an increased risk of prostate cancer, and it is yet unknown if it is related to other hormone-dependent cancers, such as breast cancer or whether this association could be considered causal. METHODS: We examined the association between the phototype and breast and prostate cancers using a Mendelian randomization analysis. We studied 1,738 incident cases of breast cancer and another 817 cases of prostate cancer. To perform a Mendelian randomization analysis on the phototype-cancer relationship, a genetic pigmentation score was required that met the following criteria: (1) the genetic pigmentation score was associated with phototype in controls; (2) the genetic pigmentation score was not associated with confounders in the relationship between phototype and cancer, and (3) the genetic pigmentation score was associated with cancer only through its association with phototype. Once this genetic score is available, the association between genetic pigmentation score and cancer can be identified as the association between phototype and cancer. RESULTS: The association between the genetic pigmentation score and phototype in controls showed that a higher genetic pigmentation score was associated with fair skin, blond hair, blue eyes and the presence of freckles. Applying the Mendelian randomization analysis, we verified that there was no association between the genetic pigmentation score and cancers of the breast and prostate. CONCLUSIONS: Phototype is not associated with breast or prostate cancer.

19.
Sci Transl Med ; 10(453)2018 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-30089634

RESUMO

Neuropathic pain is a debilitating chronic syndrome that is often refractory to currently available analgesics. Aberrant expression of several microRNAs (miRNAs) in nociception-related neural structures is associated with neuropathic pain in rodent models. We have exploited the antiallodynic phenotype of mice lacking the bone morphogenetic protein and activin membrane-bound inhibitor (BAMBI), a transforming growth factor-ß (TGF-ß) pseudoreceptor. We used these mice to identify new miRNAs that might be useful for diagnosing, treating, or predicting neuropathic pain. We show that, after sciatic nerve injury in rats, miR-30c-5p was up-regulated in the spinal cord, dorsal root ganglia, cerebrospinal fluid (CSF) and plasma and that the expression of miR-30c-5p positively correlated with the severity of allodynia. The administration of a miR-30c-5p inhibitor into the cisterna magna of the brain delayed neuropathic pain development and reversed fully established allodynia in rodents. The mechanism was mediated by TGF-ß and involved the endogenous opioid system. In patients with neuropathic pain associated with leg ischemia, the expression of miR-30c-5p was increased in plasma and CSF compared to control patients without pain. Logistic regression analysis in our cohort of patients showed that the expression of miR-30c-5p in plasma and CSF, in combination with other clinical variables, might be useful to help to predict neuropathic pain occurrence in patients with chronic peripheral ischemia.

20.
Oncotarget ; 9(56): 30869-30882, 2018 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-30112114

RESUMO

Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related deaths worldwide. There is increasing interest in developing specific markers to serve as predictors of response to sorafenib and to guide targeted therapy. Using a sequencing platform designed to study somatic mutations in a selection of 112 genes (HepatoExome), we aimed to characterize lesions from HCC patients and cell lines, and to use the data to study the biological and mechanistic effects of case-specific targeted therapies used alone or in combination with sorafenib. We characterized 331 HCC cases in silico and 32 paired samples obtained prospectively from primary tumors of HCC patients. Each case was analyzed in a time compatible with the requirements of the clinic (within 15 days). In 53% of the discovery cohort cases, we detected unique mutational signatures, with up to 34% of them carrying mutated genes with the potential to guide therapy. In a panel of HCC cell lines, each characterized by a specific mutational signature, sorafenib elicited heterogeneous mechanistic and biological responses, whereas targeted therapy provoked the robust inhibition of cell proliferation and DNA synthesis along with the blockage of AKT/mTOR signaling. The combination of sorafenib with targeted therapies exhibited synergistic anti-HCC biological activity concomitantly with highly effective inhibition of MAPK and AKT/mTOR signaling. Thus, somatic mutations may lead to identify case-specific mechanisms of disease in HCC lesions arising from multiple etiologies. Moreover, targeted therapies guided by molecular characterization, used alone or in combination with sorafenib, can effectively block important HCC disease mechanisms.

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