Low-density Lipoprotein Cholesterol And Radiotherapy-induced Carotid Atherosclerosis In Subjects With Head And Neck Cancer

Background: Radiotherapy (RT) is a risk factor for accelerated carotid artery atherosclerotic disease in subjects with head and neck cancer. However, the risk factors of RT-induced carotid artery remodeling are not established. This study aimed to investigate the effects of RT on carotid and popliteal arteries in subjects with head and neck cancer and to evaluate the relationship between baseline clinical and laboratory features and the progression of RT-induced atherosclerosis.Findings: Eleven men (age = 57.9 ± 6.2years) with head and neck cancer who underwent cervical bilateral irradiation were prospectively examined by clinical and laboratory analysis and by carotid and popliteal ultrasound before and after treatment (mean interval between the end of RT and the post-RT assessment = 181 ± 47 days). No studied subject used hypocholesterolemic medications. Significant increases in carotid intima-media thickness (IMT) (0.95 ± 0.08 vs. 0.87 ± 0.05 mm; p 3.0.CO;2-X, 626923Pereira Lima, M.N., Biolo, A., Foppa, M., da Rosa, P.R., Rohde, L.E., Clausell, N., A prospective, comparative study on the early effects of local and remote radiation therapy on carotid intima-media thickness and vascular cellular adhesion molecule-1 in patients with head and neck and prostate tumors (2011) Radiother Oncol, 101, pp. 449-453. , 10.1016/j.radonc.2010.03.026, 20435360Kalábová, H., Melichar, B., Ungermann, L., Doležal, J., Krčmová, L., Kašparová, M., Plíšek, J., Solichová, D., Intima-media thickness, myocardial perfusion and laboratory risk factors of atherosclerosis in patients with breast cancer treated with anthracycline-based chemotherapy (2011) Med Oncol, 28, pp. 1281-1287. , 10.1007/s12032-010-9593-1, 20567943Muzaffar, K., Collins, S.L., Labropoulos, N., Baker, W.H., A prospective study of the effects of irradiation on the carotid artery (2000) Laryngoscope, 110, pp. 1811-1814. , 10.1097/00005537-200011000-00007, 11081590Faruolo, M., Fiorentino, A., Gallucci, G., Lapadula, L., Fusco, V., Intimal-medial thickness and carotid arteries lumen in irradiated patients for head and neck cancer: preliminary data of an observational study (2013) Clin Transl Oncol, 15, pp. 861-864. , 10.1007/s12094-013-1023-3, 23463595Ferreira-Sae, M.C., Cipolli, J.A., Cornélio, M.E., Matos-Souza, J.R., Fernandes, M.N., Schreiber, R., Costa, F.O., Nadruz, W., Sodium intake is associated with carotid artery structure alterations and plasma matrix metalloproteinase-9 upregulation in hypertensive adults (2011) J Nutr, 141, pp. 877-882. , 10.3945/jn.110.135921, 21430243Gemignani, T., Azevedo, R.C., Higa, C.M., Coelho, O.R., Matos-Souza, J.R., Nadruz, W., Increased popliteal circumferential wall tension induced by orthostatic body posture is associated with local atherosclerotic plaques (2012) Atherosclerosis, 224, pp. 118-122. , 10.1016/j.atherosclerosis.2012.06.069, 2281862

Racial disparities in risks of stroke

To the Editor: The incidence of stroke in the United States has been decreasing as efforts have been made to control vascular risk factors. However, the extent to which modifications in changes in the risk of stroke have occurred in blacks as compared with whites has not been widely studied

Widening racial differences in risks for coronary heart disease

The incidence of coronary heart disease (CHD) has been declining in the United States, but these improvements appear to be lagging in blacks compared to whites. To understand racebased patterns in contributions to risk over time, we investigated temporal trends in the prevalence of major risk factors and their attributable hazards for CHD in a large sample of black and white adults living in 4 different communities and followed over the last two decades

Declining Lung Function and Cardiovascular Risk: The ARIC Study

Background: Pulmonary dysfunction predicts incident cardiovascular disease (CVD). Objectives: The purpose of this study was to evaluate whether longitudinal decline in lung function is associated with incident heart failure (HF), coronary heart disease (CHD), and stroke. Methods: Among 10,351 participants in the ARIC (Atherosclerosis Risk In Communities) study free of CVD, rapid lung function decline was defined as the greatest quartile (n = 2,585) of decline in either forced expiratory volume in 1 s (FEV1) (>1.9% decline/year) or forced vital capacity (FVC) (>2.1% decline/year) over 2.9 ± 0.2 years. The relationship between rapid decline in FEV1 or FVC and subsequent incident HF, CHD, stroke, or a composite of these was assessed using multivariable Cox regression adjusting for the baseline spirometry value, demographics, height, body mass index, heart rate, diabetes, hypertension, low-density lipoprotein, use of lipid-lowering medication, N-terminal fragment of prohormone for B-type natriuretic peptide, and smoking. Results: The mean age was 54 ± 6 years, 56% were women, and 81% were white. At 17 ± 6 years of follow-up, HF occurred in 14%, CHD 11%, stroke 6%, and the composite in 24%. Rapid decline in FEV1 and in FVC were both associated with a heightened risk of incident HF (hazard ratio [HR]: 1.17; 95% confidence interval [CI]: 1.04 to 1.33; p = 0.010; and HR: 1.27; 95% CI: 1.12 to 1.44; p < 0.001; respectively), with rapid decline in FEV1 most prognostic in the first year of follow-up (HR: 4.22; 95% CI: 1.34 to 13.26; p = 0.01). Rapid decline in FEV1 was also associated with incident stroke (HR: 1.25; 95% CI: 1.04 to 1.50; p = 0.015). Conclusions: A rapid decline in lung function, assessed by serial spirometry, is associated with a higher incidence of subsequent CVD, particularly incident HF

The C242T polymorphism of the p22-phox gene (CYBA) is associated with higher left ventricular mass in Brazilian hypertensive patients

<p>Abstract</p> <p>Background</p> <p>Reactive oxygen species have been implicated in the physiopathogenesis of hypertensive end-organ damage. This study investigated the impact of the C242T polymorphism of the p22-phox gene (CYBA) on left ventricular structure in Brazilian hypertensive subjects.</p> <p>Methods</p> <p>We cross-sectionally evaluated 561 patients from 2 independent centers [Campinas (n = 441) and Vitória (n = 120)] by clinical history, physical examination, anthropometry, analysis of metabolic and echocardiography parameters as well as p22-phox C242T polymorphism genotyping. In addition, NADPH-oxidase activity was quantified in peripheral mononuclear cells from a subgroup of Campinas sample.</p> <p>Results</p> <p>Genotype frequencies in both samples were consistent with the Hardy- Weinberg equilibrium. Subjects with the T allele presented higher left ventricular mass/height^2.7than those carrying the CC genotype in Campinas (76.8 ± 1.6 vs 70.9 ± 1.4 g/m^2.7; p = 0.009), and in Vitória (45.6 ± 1.9 vs 39.9 ± 1.4 g/m^2.7; p = 0.023) samples. These results were confirmed by stepwise regression analyses adjusted for age, gender, blood pressure, metabolic variables and use of anti-hypertensive medications. In addition, increased NADPH-oxidase activity was detected in peripheral mononuclear cells from T allele carriers compared with CC genotype carriers (p = 0.03).</p> <p>Conclusions</p> <p>The T allele of the p22-phox C242T polymorphism is associated with higher left ventricular mass/height^2.7and increased NADPH-oxidase activity in Brazilian hypertensive patients. These data suggest that genetic variation within NADPH-oxidase components may modulate left ventricular remodeling in subjects with systemic hypertension.</p

Stretch-Induced Stress Fiber Remodeling and the Activations of JNK and ERK Depend on Mechanical Strain Rate, but Not FAK

BACKGROUND: Cells within tissues are subjected to mechanical forces caused by extracellular matrix deformation. Cells sense and dynamically respond to stretching of the matrix by reorienting their actin stress fibers and by activating intracellular signaling proteins, including focal adhesion kinase (FAK) and the mitogen-activated proteins kinases (MAPKs). Theoretical analyses predict that stress fibers can relax perturbations in tension depending on the rate of matrix strain. Thus, we hypothesized stress fiber organization and MAPK activities are altered to an extent dependent on stretch frequency. PRINCIPAL FINDINGS: Bovine aortic endothelial cells and human osteosarcoma cells expressing GFP-actin were cultured on elastic membranes and subjected to various patterns of stretch. Cyclic stretching resulted in strain rate-dependent increases in stress fiber alignment, cell retraction, and the phosphorylation of the MAPKs JNK, ERK and p38. Transient step changes in strain rate caused proportional transient changes in the levels of JNK and ERK phosphorylations without affecting stress fiber organization. Disrupting stress fiber contractile function with cytochalasin D or Y27632 decreased the levels of JNK and ERK phosphorylation. Previous studies indicate that FAK is required for stretch-induced cell alignment and MAPK activations. However, cyclic uniaxial stretching induced stress fiber alignment and the phosphorylation of JNK, ERK and p38 to comparable levels in FAK-null and FAK-expressing mouse embryonic fibroblasts. CONCLUSIONS: These results indicate that cyclic stretch-induced stress fiber alignment, cell retraction, and MAPK activations occur as a consequence of perturbations in fiber strain. These findings thus shed new light into the roles of stress fiber relaxation and reorganization in maintenance of tensional homeostasis in a dynamic mechanical environment

Psychometric performance of the brazilian version of the Mini-cuestionario de calidad de vida en la hipertensión arterial (MINICHAL)

This study aimed to evaluate the feasibility, acceptability, ceiling and floor effects, reliability, and convergent construct validity of the Brazilian version of the Mini Cuestionario de Calidad de Vida en la Hipertensión Arterial (MINICHAL). The study included 200 hypertensive outpatients in a university hospital and a primary healthcare unit. The MINICHAL was applied in 3.0 (± 1.0) minutes with 100% of the items answered. A "ceiling effect" was observed in both dimensions and in the total score, as well as evidence of measurement stability (ICC=0.74). The convergent validity was confirmed by significant positive correlations between similar dimensions of the MINICHAL and the SF-36, and significant negative correlations with the Minnesota Living with Heart Failure Questionnaire - MLHFQ, however, correlations between dissimilar constructs were also observed. It was concluded that the Brazilian version of the MINICHAL presents evidence of reliability and validity when applied to hypertensive outpatientsEste estudio tuvo como objetivo evaluar la practicidad, la aceptabilidad, los efectos techo y suelo, la confiabilidad y la validez de constructo convergente de la versión brasileña del Minicuestionario de Calidad de Vida de la Hipertensión Arterial - MINICHAL. Participaron del estudio 200 pacientes hipertensos en seguimiento en ambulatorio, en hospital universitario y en Unidad Básica de Salud. El MINICHAL fue aplicado en 3,0 (±1,0) minutos, con 100% de los ítems respondidos. Fue observado "efecto techo" en ambas dimensiones y puntaje total, así como evidencias de estabilidad de la medida (CCI=0,74). La validez convergente fue confirmada por correlaciones significativas positivas entre dimensiones similares del MINICHAL y del SF-36, y por correlaciones significativas negativas con el Minnesota Living with Heart Failure Questionnaire - MLHFQ, a pesar de que correlaciones entre constructos no similares hubiesen sido observadas. Se concluye que la versión brasileña del MINICHAL presenta evidencia de confiabilidad y validez cuando aplicada en hipertensos en seguimiento en ambulatorio.Este estudo teve como objetivo avaliar a praticabilidade, a aceitabilidade, os efeitos teto e chão, a confiabilidade e a validade de constructo convergente da versão brasileira do mini - cuestionario de calidad de vida en la hipertensión arterial - Minichal. Participaram do estudo 200 pacientes hipertensos, em seguimento ambulatorial, em hospital universitário e unidade básica de saúde. O Minichal foi aplicado em 3,0 (±1,0) minutos, com 100% dos itens respondidos. Foi observado efeito teto em ambas as dimensões e escore total, bem como evidências de estabilidade da medida (ICC=0,74). A validade convergente foi confirmada por correlações significativas positivas entre dimensões similares do Minichal e do SF-36, e por correlações significativas negativas com o Minnesota Living with Heart Failure Questionnaire - MLHFQ, embora correlações entre constructos dissimilares tenham sido observadas. Conclui-se que a versão brasileira do Minichal apresenta evidência de confiabilidade e validade, quando aplicada em hipertensos, em seguimento ambulatorial

Vertebrate Paralogous MEF2 Genes: Origin, Conservation, and Evolution

BACKGROUND: The myocyte enhancer factor 2 (MEF2) gene family is broadly expressed during the development and maintenance of muscle cells. Although a great deal has been elucidated concerning MEF2 transcription factors' regulation of specific gene expression in diverse programs and adaptive responses, little is known about the origin and evolution of the four members of the MEF2 gene family in vertebrates. METHODOLOGY/PRINCIPAL FINDINGS: By phylogenetic analyses, we investigated the origin, conservation, and evolution of the four MEF2 genes. First, among the four MEF2 paralogous branches, MEF2B is clearly distant from the other three branches in vertebrates, mainly because it lacks the HJURP_C (Holliday junction recognition protein C-terminal) region. Second, three duplication events might have occurred to produce the four MEF2 paralogous genes and the latest duplication event occurred near the origin of vertebrates producing MEF2A and MEF2C. Third, the ratio (K(a)/K(s)) of non-synonymous to synonymous nucleotide substitution rates showed that MEF2B evolves faster than the other three MEF2 proteins despite purifying selection on all of the four MEF2 branches. Moreover, a pair model of M0 versus M3 showed that variable selection exists among MEF2 proteins, and branch-site analysis presented that sites 53 and 64 along the MEF2B branch are under positive selection. Finally, and interestingly, substitution rates showed that type II MADS genes (i.e., MEF2-like genes) evolve as slowly as type I MADS genes (i.e., SRF-like genes) in animals, which is inconsistent with the fact that type II MADS genes evolve much slower than type I MADS genes in plants. CONCLUSION: Our findings shed light on the relationship of MEF2A, B, C, and D with functional conservation and evolution in vertebrates. This study provides a rationale for future experimental design to investigate distinct but overlapping regulatory roles of the four MEF2 genes in various tissues

ICTERUS - A computer-based-learning for porphirins and bilirrubin metabolism

Abstract of the panel presented at the SBBq annual meeting (see attached)