Sudden cardiac death in patients with ischemic heart failure undergoing coronary artery bypass grafting results from the STICH randomized clinical trial (Surgical Treatment for Ischemic Heart Failure)

Background—The risk of sudden cardiac death (SCD) in patients with heart failure following CABG has not been examined in a contemporary clinical trial of surgical revascularization. This analysis describes the incidence, timing and clinical predictors of SCD after CABG. Methods—Patients enrolled in the Surgical Treatment of Ischemic Heart Failure (STICH) trial who underwent CABG with or without surgical ventricular reconstruction (SVR) were included. We excluded patients with prior ICD and those randomized only to medical therapy. The primary outcome was SCD as adjudicated by a blinded committee. A Cox model was used to examine and identify predictors of SCD. The Fine and Gray method was used to estimate the incidence of SCD accounting for the competing risk of other deaths. Results—Over a median follow-up of 46 months, 113 patients of 1411 patients who received CABG without (n = 934) or with SVR (n = 477) had SCD; 311 died of other causes. The mean LVEF at enrollment was 28±9%. The 5-year cumulative incidence of SCD was 8.5%. Patients who had SCD and those who did not die were younger and had fewer comorbid conditions than those who died for reasons other than SCD. In the first 30 days after CABG, SCD (n=5) accounted for 7% of all deaths. The numerically greatest monthly rate of SCD was in the 31-90 day time period. In a multivariable analysis including baseline demographics, risk factors, coronary anatomy and LV function, ESVI and BNP were most strongly associated with SCD. Conclusions—The monthly risk of SCD shortly after CABG among patients with a low LVEF is highest between the first and third month, suggesting that risk stratification for SCD should occur early in the postoperative period, particularly in patients with increased preoperative ESVI and/or BNP

Transcription-dependent spatial arrangements of CFTR and adjacent genes in human cell nuclei

We investigated in different human cell types nuclear positioning and transcriptional regulation of the functionally unrelated genes GASZ, CFTR, and CORTBP2, mapping to adjacent loci on human chromosome 7q31. When inactive, GASZ, CFTR, and CORTBP2 preferentially associated with the nuclear periphery and with perinuclear heterochromatin, whereas in their actively transcribed states the gene loci preferentially associated with euchromatin in the nuclear interior. Adjacent genes associated simultaneously with these distinct chromatin fractions localizing at different nuclear regions, in accordance with their individual transcriptional regulation. Although the nuclear localization of CFTR changed after altering its transcription levels, the transcriptional status of CFTR was not changed by driving this gene into a different nuclear environment. This implied that the transcriptional activity affected the nuclear positioning, and not vice versa. Together, the results show that small chromosomal subregions can display highly flexible nuclear organizations that are regulated at the level of individual genes in a transcription-dependent manner

Efeito dose-dependente da l-arginina em parâmentros cardiorrespiratórios e performance física em sujeito hipertenso: um estudo de caso clínico

A hipertensão arterial representa um fator e risco independente, linear e contínuo para doenças do coração. O objetivo deste estudo foi analisar o efeito hipotensivo da L-arginina (L-Arg) em sujeito hipertenso limítrofe. Participou do estudo um sujeito do sexo masculino, com 52 anos de idade, índice de massa corporal (IMC)=19,2kg.m-2 e consumo máximo de oxigênio (VO2máx)=39mL.kg-1.min-1. O sujeito foi submetido a três situações experimentais para avaliar o efeito hipotensivo, dose dependente da suplementação com L-Arg em parâmetros de exercício e repouso. Os testes foram realizados submetendo o sujeito a um exercício aeróbico (60% da FCR) durante 30 minutos na esteira ergométrica. Foram realizadas três avaliações (controle, suplementado com 2g de L-Arg por 4 dias e placebo) com intervalo de 7 dias entre o controle e a suplementação e 14 dias entre suplementação e placebo. A pressão arterial foi aferida com intervalos de dois minutos, bem como a FC (freqüência cardíaca) e escala subjetiva de esforço. Os resultados demonstraram uma queda nos níveis pressóricos quando se utilizou L-arginina bem como na situação placebo, a FC teve substancial queda quando se utilizou L-arginina em comparação com as outras duas situações. O sujeito indicou uma menor sensação de esforço quando suplementado. Conclui-se que houve um efeito crônico após a retirada do suplemento, sugerindo assim que novos estudos sejam feitos para investigar tais efeitos em diferentes dosagens e prazos de suplementação, haja vista que, poucas referências foram encontradas na literatura

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Efeito da suplementação com maltotextrina e cafeína durante exercício aeróbico em parâmetros cardiorrespiratórios e metabólicos em paciente diabético

O Diabetes Mellitus Tipo 2 é uma doença crônica que está afetando a população de forma crescente, tornando-se um sério problema de Saúde Pública. A suplementação esportiva como forma de prevenção da hipoglicemia para esses indivíduos pode favorecer a prática de exercícios físicos. O objetivo do presente trabalho, caracterizado como estudo de caso, foi investigar o efeito da suplementação com maltodextrina com ação isolada e também associada à cafeína em parâmetros metabólicos e cardivasculares. A metodologia utilizada foi a de indução de atividade física utilizando protocolo de esteira, com suplementação de substância controle (placebo), maltodextrina e cafeína de forma isolada em um primeiro momento e em associação em um segundo momento. A hipótese a ser testada refere-se a prevenção da instalação de quadro hipoglicêmico em paciente portador de Diabetes Mellitus Tipo 2 com 67 anos, percentual de gordura > 35%, sedentário, (VO2máx) = 20,92 mL.Kg-1.min-1, glicemia de jejum de 184 mmol, com relato de mal estar durante a prática de exercício físico leve, provavelmente ocasionada pela queda no valor de glicemia. O trabalho cardíaco se manteve estável nos 3 tratamentos. De forma isolada, a cafeína não proporcionou alteração significativa na glicemia. A suplementação com maltodextrina, de forma isolada e associada a cafeína foi eficiente para minimização dos efeitos de hipoglicemia esperados. A pressão arterial e freqüência cardíaca não apresentaram resultado conclusivo e necessitam de mais estudos para verificação da interação entre fármacos utilizados pelo paciente em associação aos tratamentos

The adaptation of the Affective Norms for English Words (ANEW) for European Portuguese

This study presents the adaptation of the Affective Norms for English Words (ANEW; Bradley & Lang, 1999a) for European Portuguese (EP). The EP adaptation of the ANEW was based on the affective ratings made by 958 college students who were EP native speakers. Participants assessed about 60 words by considering the affective dimensions of valence, arousal, and dominance, using the Self-Assessment Manikin (SAM) in either a paper-and-pencil and a web survey procedures. Results of the adaptation of the ANEW for EP are presented. Furthermore, the differences between EP, American (Bradley & Lang, 1999a), and Spanish (Redondo, Fraga, Padrón, & Comesaña, 2007) standardizations were explored. Results showed that the ANEW words were understood in a similar way by EP, American, and Spanish subjects, although some sex and cross-cultural differences were observed. The EP adaptation of the ANEW is shown to be a valid and useful tool that will allow researchers to control and/or manipulate the affective properties of stimuli as well as to develop cross-linguistic studies. The normative values of EP adaptation of the ANEW can be downloaded at http://brm.psychonomic-journals.org/content/supplemental.COMPETE - Programa Operacional Factores de CompetitividadeFundo Europeu de Desenvolvimento Regional - FEDERQuadro de Referência Estratégico Nacional - QRENFundação para a Ciência e a Tecnologia (FCT) - research project “Procura Palavras (P-Pal ): A software program for deriving objective and subjective psycholinguistic indices for European Portuguese words

HEX expression and localization in normal mammary gland and breast carcinoma

BACKGROUND: The homeobox gene HEX is expressed in several cell types during different phases of animal development. It encodes for a protein localized in both the nucleus and the cytoplasm. During early mouse development, HEX is expressed in the primitive endoderm of blastocyst. Later, HEX is expressed in developing thyroid, liver, lung, as well as in haematopoietic progenitors and endothelial cells. Absence of nuclear expression has been observed during neoplastic transformation of the thyroid follicular cells. Aim of the present study was to evaluate the localization and the function of the protein HEX in normal and tumoral breast tissues and in breast cancer cell lines. METHODS: HEX expression and nuclear localization were investigated by immunohistochemistry in normal and cancerous breast tissue, as well as in breast cancer cell lines. HEX mRNA levels were evaluated by real-time PCR. Effects of HEX expression on Sodium Iodide Symporter (NIS) gene promoter activity was investigated by HeLa cell transfection. RESULTS: In normal breast HEX was detected both in the nucleus and in the cytoplasm. In both ductal and lobular breast carcinomas, a great reduction of nuclear HEX was observed. In several cells from normal breast tissue as well as in MCF-7 and T47D cell line, HEX was observed in the nucleolus. MCF-7 treatment with all-trans retinoic acid enhanced HEX expression and induced a diffuse nuclear localization. Enhanced HEX expression and diffuse nuclear localization were also obtained when MCF-7 cells were treated with inhibitors of histone deacetylases such as sodium butyrate and trichostatin A. With respect to normal non-lactating breast, the amount of nuclear HEX was greatly increased in lactating tissue. Transfection experiments demonstrated that HEX is able to up-regulate the activity of NIS promoter. CONCLUSION: Our data indicate that localization of HEX is regulated in epithelial breast cells. Since modification of localization occurs during lactation and tumorigenesis, we suggest that HEX may play a role in differentiation of the epithelial breast cell