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1.
Psychiatry Res ; 279: 315-322, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31196691

RESUMO

BACKGROUND: Repetitive Transcranial Magnetic Stimulation (rTMS) has been suggested as an alternative treatment to postnatal depression (PPD). OBJECTIVES: This systematic review aims to examine and summarise evidence on rTMS efficacy in treating depression during the postnatal period. METHODS: We included randomized and non-randomized, single arm, and case report studies, with active rTMS and theta-burst stimulation, sham rTMS, pharmacotherapy or no treatment as comparators. Participants included women with PPD, who were administered rTMS after delivery and up to 12 months postpartum. The observed outcomes were response rate and acceptability. RESULTS: rTMS shows promising results, with clinically significant decreases in Edinburgh Postnatal Depression Scale (EPDS) scores at week 4 and an overall low risk of dropout. LIMITATIONS: The reduced number of reports, the lack of complete datasets and the serious/high risk of bias of the studies warrant cautious interpretations. CONCLUSIONS AND IMPLICATIONS: Despite the promising results, existing evidence on rTMS efficacy is limited, and questions remain on what the most beneficial stimulation parameters should be. Future multicentre randomized clinical trials are needed to better ascertain the clinical efficacy of rTMS in the treatment of depression in the postpartum period.

2.
Hum Mutat ; 40(5): 566-577, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30817846

RESUMO

There is still around 50% of the familial breast cancer (BC) cases with an undefined genetic cause, here we have used next-generation sequencing (NGS) technology to identify new BC susceptibility genes. This approach has led to the identification of RECQL5, a member of RECQL-helicases family, as a new BC susceptibility candidate, which deserves further study. We have used a combination of whole exome sequencing in a family negative for mutations in BRCA1/2 throughout (BRCAX), in which we found a probably deleterious variant in RECQL5, and targeted NGS of the complete coding regions and exon-intron boundaries of the candidate gene in 699 BC Spanish BRCAX families and 665 controls. Functional characterization and in silico inference of pathogenicity were performed to evaluate the deleterious effect of detected variants. We found at least seven deleterious or likely deleterious variants among the cases and only one in controls. These results prompt us to propose RECQL5 as a gene that would be worth to analyze in larger studies to explore its possible implication in BC susceptibility.

3.
Mol Oncol ; 13(5): 1110-1120, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30747491

RESUMO

Single nucleotide polymorphisms (SNPs) in DNA glycosylase genes involved in the base excision repair (BER) pathway can modify breast and ovarian cancer risk in BRCA1 and BRCA2 mutation carriers. We previously found that SNP rs34259 in the uracil-DNA glycosylase gene (UNG) might decrease ovarian cancer risk in BRCA2 mutation carriers. In the present study, we validated this finding in a larger series of familial breast and ovarian cancer patients to gain insights into how this UNG variant exerts its protective effect. We found that rs34259 is associated with significant UNG downregulation and with lower levels of DNA damage at telomeres. In addition, we found that this SNP is associated with significantly lower oxidative stress susceptibility and lower uracil accumulation at telomeres in BRCA2 mutation carriers. Our findings help to explain the association of this variant with a lower cancer risk in BRCA2 mutation carriers and highlight the importance of genetic changes in BER pathway genes as modifiers of cancer susceptibility for BRCA1 and BRCA2 mutation carriers.

4.
J Electrocardiol ; 52: 11-16, 2018 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-30476632

RESUMO

BACKGROUND: The potential for thromboembolism in atrial flutter (AFL) is different from atrial fibrillation. AFL cycle length (AFL-CL) may be related to reduced left atrial appendage (LAA) function. Very rapid AFL-CL can lead to mechanical and electrophysiological disorders that contribute to lower LAA emptying velocity (LAEV). The aim of this study is to relate atrial flutter cycle length with LAEV and its role in thrombogenesis. METHODS: Cross-sectional study of patients with atrial flutter AFL who underwent transoesophageal echocardiography (TEE) before catheter ablation or electric cardioversion. AFL-CL in milliseconds was measured with a 12-lead EKG or in intracardiac records. RESULTS: We included 123 patients. There was correlation between AFL-CL and LAEV (r = 0.34; p = 0.003) in typical AFL. Cycle length, LA size and atypical flutter were predictors of low LAEV on multivariate analysis. An index multiplying atrial rate (bpm) during the arrhythmia versus left atrial size(mm) >11,728 was associated with spontaneous echogenic contrast and/or left atrial thrombus on TEE (C-statistic = 0.71; CI95%0.60-0.81). CONCLUSIONS: There was a significant relationship between the AFL-CL and LAEV. The LAEV was affected by the LA size, the type of atrial flutter and the AFL-CL. A new index, relating the atrial rate with the left atrial size, was able to identify a higher occurrence of spontaneous echogenic contrast and/or left atrial thrombus.

5.
Dev Med Child Neurol ; 2018 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-30451290

RESUMO

AIM: Our aim was to review available studies which test transcranial direct current stimulation (tDCS) to reduce symptom severity in children with autism spectrum disorder (ASD). METHOD: We performed a systematic scoping review in PubMed and PsychINFO databases for studies employing tDCS in children and adolescents with ASD. RESULTS: We found five studies (two small randomized controlled studies, one experimental study, one quasi-experimental study, and one case study) reporting positive effects of tDCS in ASD symptom reduction. Study design varied greatly and sample size ranged from 1 to 20 patients. INTERPRETATION: Preliminary evidence is encouraging of the potential usefulness of tDCS for treatment of ASD in children and adolescents. It suggests tentative support for reductions in symptom severity and, according to parental reports and clinical observations, improvements in some aspects of language. However, the evidence is sparse and of low quality, so the true effect of tDCS is likely to be substantially different from the estimate of effect in this review. Therefore, future randomized controlled trials are needed to draw conclusions regarding tDCS efficacy in paediatric samples with ASD. WHAT THIS PAPER ADDS: There is low confidence in the estimate of effect, but tentatively encouraging results warrant further investigation.

6.
Rev Saude Publica ; 52: 73, 2018 Jul 26.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-30066810

RESUMO

OBJECTIVE: To analyze the influence of the socioeconomic context of the community on chronic child malnutrition in Colombia. METHODS: We estimated multilevel logistic models using data from the National Demographic and Health Survey in Colombia in 2010. The final sample included 11,448 children under the age of five gathered in 3,528 communities. In addition, we used the Principal Component Analysis with polychoric correlations for the construction of composed indicators of wealth, autonomy of the woman, and the use and access to the health system. RESULTS: The average level of community wealth was significantly and independently associated with chronic malnutrition in early childhood, more than the socioeconomic status of the household itself. At the individual and household level, the probability of chronic malnutrition was higher for children from mothers with low levels of autonomy and use and access to the health system, mothers who had their first child in adolescence, and mothers who live in homes in the lowest wealth quintiles. In contrast, children from mothers with a body mass index > 25 and with at least secondary education (versus no education) were less likely to suffer from chronic malnutrition. CONCLUSIONS: Research, programs, and interventions need to take into account the physical, economic, and social context of communities to contribute with the improvement of the nutritional status of early childhood in Colombia.


Assuntos
Transtornos da Nutrição Infantil/epidemiologia , Desnutrição/epidemiologia , Fatores Socioeconômicos , Distribuição por Idade , Fatores Etários , Transtornos da Nutrição Infantil/etiologia , Pré-Escolar , Doença Crônica/epidemiologia , Colômbia/epidemiologia , Estudos Transversais , Características da Família , Feminino , Indicadores Básicos de Saúde , Humanos , Lactente , Recém-Nascido , Modelos Logísticos , Masculino , Desnutrição/etiologia , Mães/estatística & dados numéricos , Análise Multinível , Inquéritos Nutricionais , Fatores de Risco , Distribuição por Sexo , Fatores Sexuais
7.
J Autism Dev Disord ; 2018 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-30143949

RESUMO

This study compared maternal responsiveness to children with two neurodevelopmental disorders sharing different but, in some cases, overlapping social phenotypes-Williams syndrome (WS) and autism spectrum disorder (ASD)-and explored the relations between maternal responsiveness and child emotional/behavioural problems (EBP). The sample included 16 pre-schoolers with WS and 43 with ASD, and their mothers. Responsiveness was assessed during a mother-child interaction task. Mothers completed the CBCL 1½-5, providing a measure of EBP. No significant differences emerged between groups, and most dyads were characterized by less responsive behaviours. Maternal responsiveness proved related to child developmental age, but not with EBP. These results provide further insight into the rearing environment of children with neurodevelopmental disorders, highlighting the need for early relationship-based interventions.

8.
Psicol. teor. prát ; 20(1): 179-188, Jan.-Apr. 2018. ilus
Artigo em Inglês | LILACS-Express | ID: biblio-895928

RESUMO

Initially, eye tracking technology concerned more adults, however, over the last decades, it has shown great promise in infant research, with several studies demonstrating that its use can provide essential data on the emergence and development of cognitive, social and, emotional processes in childhood. This article aimed at systematizing information regarding the use of eye tracking in infants, including the types of trackers available, their advantages and disadvantages, as well as to present some recent studies. Although there are a significant amount and variety of studies with this approach worldwide, Brazilian research is still scarce. The present study analyses the usefulness of eye tracking technology in infant samples to assist researchers in their methodological decisions, and extend its applicability beyond existing studies.


A técnica de rastreamento ocular foi inicialmente dirigida a adultos, no entanto, ao longo das últimas décadas, tem se mostrado muito promissora em pesquisa com bebês, com diversos estudos demonstrando que sua utilização pode fornecer dados importantes sobre o surgimento e o desenvolvimento de processos cognitivos, sociais e emocionais na infância. O objetivo deste trabalho é sistematizar informações relativas ao uso do rastreamento ocular em bebês, incluindo seu histórico, os tipos de rastreadores disponíveis e suas vantagens e desvantagens, além de citar exemplos de estudos recentes. Embora exista uma quantidade e variedade significativa de estudos com essa abordagem em âmbito internacional, as publicações nacionais são escassas. O presente estudo apresenta uma análise da utilidade do rastreamento ocular em amostras infantis, a fim de auxiliar os pesquisadores na tomada de decisões metodológicas e estender sua aplicabilidade para além dos estudos existentes.


La técnica de rastreo ocular fue inicialmente dirigida a adultos, pero a lo largo de las últimas décadas, se ha mostrado muy prometedora en investigación con bebés, siendo que diversos estudios han demostrado que su utilización puede proporcionar hallazgos significativos sobre el surgimiento y desarrollo de aspectos cognitivos, sociales y sociales emocionales en la infancia. El objetivo de esta revisión teórica es sistematizar informaciones relativas al uso del rastreo ocular en bebés, incluyendo su historial, los tipos de rastreadores disponibles y sus ventajas y desventajas, además de citar algunos estudios actuales. Aunque existe una cantidad y variedad significativa de estudios con este enfoque a nivel internacional, las publicaciones nacionales son escasas. El presente estudio abordará un análisis general del rastreo ocular en los bebés, a fin de estimular el uso de la técnica, ayudar a los investigadores en la toma de decisiones metodológicas, y extender su aplicabilidad más allá de los estudios existentes.

9.
Dev Psychobiol ; 60(1): 111-117, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29130483

RESUMO

Since birth, humans develop an ability to regulate their inner states and behaviors, when facing demanding situations, in order to restore calmness and engage with other persons and the surrounding environment. The present study analyzed whether 1-month infant vagal regulation to auditory stimuli was associated with later joint attention abilities-responding to and initiating joint attention-in interaction with their mothers. Twenty-three infants were assessed and measures of respiratory sinus arrhythmia-RSA (baseline and vagal tone change during auditory stimulation) were used as index of vagal regulation. At 12-months, joint attention behaviors were assessed in a 10-min toy-play mother-infant interaction. Correlational analyses showed that lower baseline RSA and larger increases in vagal tone during auditory stimulation were related to more instances of joint attention behaviors at 12 months, especially responding to joint attention. Results suggest that distinct profiles of autonomic functioning may contribute to joint attention skills.


Assuntos
Atenção/fisiologia , Percepção Auditiva/fisiologia , Comportamento do Lactente/fisiologia , Relações Mãe-Filho , Arritmia Sinusal Respiratória/fisiologia , Nervo Vago/fisiologia , Eletrocardiografia , Feminino , Humanos , Lactente , Masculino
10.
Genet Med ; 20(4): 452-457, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-28837162

RESUMO

PurposeMonoallelic germ-line mutations in the BRCA1/FANCS, BRCA2/FANCD1 and PALB2/FANCN genes confer high risk of breast cancer. Biallelic mutations in these genes cause Fanconi anemia (FA), characterized by malformations, bone marrow failure, chromosome fragility, and cancer predisposition (BRCA2/FANCD1 and PALB2/FANCN), or an FA-like disease presenting a phenotype similar to FA but without bone marrow failure (BRCA1/FANCS). FANCM monoallelic mutations have been reported as moderate risk factors for breast cancer, but there are no reports of any clinical phenotype observed in carriers of biallelic mutations.MethodsBreast cancer probands were subjected to mutation analysis by sequencing gene panels or testing DNA damage response genes.ResultsFive cases homozygous for FANCM loss-of-function mutations were identified. They show a heterogeneous phenotype including cancer predisposition, toxicity to chemotherapy, early menopause, and possibly chromosome fragility. Phenotype severity might correlate with mutation position in the gene.ConclusionOur data indicate that biallelic FANCM mutations do not cause classical FA, providing proof that FANCM is not a canonical FA gene. Moreover, our observations support previous findings suggesting that FANCM is a breast cancer-predisposing gene. Mutation testing of FANCM might be considered for individuals with the above-described clinical features.


Assuntos
Alelos , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/genética , Fragilidade Cromossômica , DNA Helicases/genética , Anemia de Fanconi/diagnóstico , Anemia de Fanconi/genética , Predisposição Genética para Doença , Mutação , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Consanguinidade , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Estudos de Associação Genética , Genótipo , Mutação em Linhagem Germinativa , Humanos , Masculino , Linhagem , Fenótipo , Medição de Risco , Fatores de Risco
11.
J Autism Dev Disord ; 48(5): 1847-1853, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29204928

RESUMO

This study examined the factor structure of the Brazilian version of the Autism-Spectrum Quotient. This is a self-report questionnaire for continuous and quantitative assessment of autistic spectrum traits in adults. Confirmatory factor analysis was performed on the five-factor model (social skill, attention switching, attention to detail, communication and imagination) proposed by the original authors, support not being found for this model in our sample. An exploratory factor analysis was then performed that resulted in an alternative three-factor model (social skills, details/patterns and imagination). Confirmatory factor analysis of the latter model revealed adequate psychometric indexes. The Brazilian version of the AQ was shown to be an adequate instrument for the evaluation of signs compatible with the autism spectrum in adults.

12.
Rev. saúde pública (Online) ; 52: 73, 2018. tab, graf
Artigo em Inglês | LILACS-Express | ID: biblio-962271

RESUMO

ABSTRACT OBJECTIVE To analyze the influence of the socioeconomic context of the community on chronic child malnutrition in Colombia. METHODS We estimated multilevel logistic models using data from the National Demographic and Health Survey in Colombia in 2010. The final sample included 11,448 children under the age of five gathered in 3,528 communities. In addition, we used the Principal Component Analysis with polychoric correlations for the construction of composed indicators of wealth, autonomy of the woman, and the use and access to the health system. RESULTS The average level of community wealth was significantly and independently associated with chronic malnutrition in early childhood, more than the socioeconomic status of the household itself. At the individual and household level, the probability of chronic malnutrition was higher for children from mothers with low levels of autonomy and use and access to the health system, mothers who had their first child in adolescence, and mothers who live in homes in the lowest wealth quintiles. In contrast, children from mothers with a body mass index > 25 and with at least secondary education (versus no education) were less likely to suffer from chronic malnutrition. CONCLUSIONS Research, programs, and interventions need to take into account the physical, economic, and social context of communities to contribute with the improvement of the nutritional status of early childhood in Colombia.


RESUMEN OBJETIVO Analizar la influencia del contexto socioeconómico de la comunidad sobre la desnutrición infantil crónica en Colombia. MÉTODOS Utilizando datos de la Encuesta Nacional de Demografía y Salud en Colombia en 2010, se estimaron modelos logísticos multinivel. La muestra final incluyó 11.448 niños menores de cinco años anidados en 3.528 comunidades. Además, se utilizó el Análisis de Componentes Principales usando correlaciones policóricas para la construcción de indicadores compuestos de riqueza, autonomía de la mujer y el uso y acceso al sistema de salud. RESULTADOS El nivel de riqueza promedio de la comunidad resultó significativa e independientemente asociado con la desnutrición crónica en la primera infancia, por encima y más allá del propio estatus socioeconómico del hogar. A nivel individual y del hogar, la probabilidad de desnutrición crónica fue mayor para niños de madres con bajos niveles de autonomía y uso y acceso al sistema de salud, que han tenido su primer hijo en la adolescencia y que viven en hogares en los quintiles más bajos de riqueza. En contraste, niños de madres con un índice de masa corporal > 25 y con al menos educación secundaria (versus sin educación) tuvieron menor probabilidad de padecer desnutrición crónica. CONCLUSIONES Investigaciones, programas e intervenciones que tengan en cuenta el contexto físico, económico y social de las comunidades son necesarias para contribuir a mejorar el estado nutricional de la primera infancia en Colombia.

13.
Braz J Cardiovasc Surg ; 32(6): 492-497, 2017 Nov-Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29267612

RESUMO

INTRODUCTION: Chronic stimulation of the right ventricle with pacemaker is associated with ventricular dyssynchrony and loss of contractility, even in subjects without previous dysfunction. In these patients, there is a debate of which pacing site is less associated with loss of ventricular function. OBJECTIVE: To compare pacemaker-induced dyssynchrony among different pacing sites in right ventricular stimulation. METHODS: Cross-sectional study of outpatients with right ventricle stimulation higher than 80% and preserved left ventricular ejection fraction. Pacing lead position (apical, medial septum or free wall) was assessed through chest X-rays. Every patient underwent echocardiogram to evaluate for dyssynchrony according to CARE-HF criteria: aortic pre-ejection time, interventricular delay and septum/posterior wall delay on M mode. RESULTS: Forty patients were included. Fifty-two percent had apical electrode position, 42% mid septum and 6% free wall. Mean QRS time 148.97±15.52 milliseconds. A weak correlation between the mean QRS width and pre-aortic ejection time (r=0.32; P=0.04) was found. No difference in QRS width among the positions could be noted. Intraventricular delay was lower in apical patients against mid septal (34.4±17.2 vs. 54.3±19.1 P<0.05) - no difference with those electrode on the free wall. No difference was noted in the pre-aortic ejection time (P=0.9). CONCLUSION: Apical pacing showed a lower interventricular conduction delay when compared to medial septum site. Our findings suggest that apical pacing dyssynchrony is not ubiquitous, as previously thought, and that it should remain an option for lead placement.

14.
Rev Peru Med Exp Salud Publica ; 34(3): 436-444, 2017 Jul-Sep.
Artigo em Espanhol | MEDLINE | ID: mdl-29267767

RESUMO

OBJECTIVES: To evaluate the effect of ZnO, TiO2 and SiO2 nanoparticles on cell viability and expression of the interleukin 7, interleukin 3, and granulocyte-macrophage colony stimulating factor (GM-CSF) genes in Mus musculus. MATERIAL AND METHODS: Red bone marrow was extracted from five Balb/c mice for the analysis of cell viability using the MTT test. The mice were divided into two groups of five each: one group was inoculated intraperitoneally with 0.5, 1.0, 2.5, 5.0, and 10 mg/kg of ZnO and SiO2 nanoparticles, respectively, and the other group was inoculated with 5.0, 10.0, 15.0, 20.0, and 25 mg/kg of TiO2 nanoparticles, respectively. Thirty hours later, RNA was extracted from the red bone marrow of the mice in both groups for gene expression analysis using quantitative PCR and RT-PCR. RESULTS: ZnO and SiO2 nanoparticles reduced cell viability in a dose-dependent manner by 37% and 26%, respectively, starting at a dose of 1 mg/kg. TiO2 nanoparticles at 5 mg/kg and 10 mg/kg reduced the gene expression of interleukins 7 and 3 by 55.3% and 70.2%, respectively, and SiO2 nanoparticles caused the greatest decrease (91%) in the expression of GM-CSF. ZnO nanoparticles reduced the expression of GM-CSF starting at doses of 20 mg/kg and 25 mg/kg. CONCLUSIONS: ZnO, SiO2 and TiO2 nanoparticles affect cell viability and gene expression in the mouse bone marrow.


Assuntos
Medula Óssea/efeitos dos fármacos , Medula Óssea/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Expressão Gênica/efeitos dos fármacos , Fator Estimulador de Colônias de Granulócitos e Macrófagos/biossíntese , Interleucina-3/biossíntese , Interleucina-7/biossíntese , Nanopartículas , Dióxido de Silício/farmacologia , Titânio/farmacologia , Óxido de Zinco/farmacologia , Animais , Fator Estimulador de Colônias de Granulócitos e Macrófagos/genética , Interleucina-3/genética , Interleucina-7/genética , Camundongos , Camundongos Endogâmicos BALB C
15.
Rev. bras. cir. cardiovasc ; 32(6): 492-497, Nov.-Dec. 2017. tab, graf
Artigo em Inglês | LILACS-Express | ID: biblio-897955

RESUMO

Abstract Introduction: Chronic stimulation of the right ventricle with pacemaker is associated with ventricular dyssynchrony and loss of contractility, even in subjects without previous dysfunction. In these patients, there is a debate of which pacing site is less associated with loss of ventricular function. Objective: To compare pacemaker-induced dyssynchrony among different pacing sites in right ventricular stimulation. Methods: Cross-sectional study of outpatients with right ventricle stimulation higher than 80% and preserved left ventricular ejection fraction. Pacing lead position (apical, medial septum or free wall) was assessed through chest X-rays. Every patient underwent echocardiogram to evaluate for dyssynchrony according to CARE-HF criteria: aortic pre-ejection time, interventricular delay and septum/posterior wall delay on M mode. Results: Forty patients were included. Fifty-two percent had apical electrode position, 42% mid septum and 6% free wall. Mean QRS time 148.97±15.52 milliseconds. A weak correlation between the mean QRS width and pre-aortic ejection time (r=0.32; P=0.04) was found. No difference in QRS width among the positions could be noted. Intraventricular delay was lower in apical patients against mid septal (34.4±17.2 vs. 54.3±19.1 P<0.05) - no difference with those electrode on the free wall. No difference was noted in the pre-aortic ejection time (P=0.9). Conclusion: Apical pacing showed a lower interventricular conduction delay when compared to medial septum site. Our findings suggest that apical pacing dyssynchrony is not ubiquitous, as previously thought, and that it should remain an option for lead placement.

16.
Arq. bras. cardiol ; 109(6): 599-605, Dec. 2017. tab
Artigo em Inglês | LILACS-Express | ID: biblio-887976

RESUMO

Abstract The best approach of multivessel coronary artery disease in the context of acute myocardial infarction with ST segment elevation and primary percutaneous coronary intervention is one of the main reasons for controversy in cardiology. Although the main global guidelines do not recommend routine complete revascularization in these patients, recent randomized clinical trials have demonstrated benefit of this approach in reducing cardiovascular outcomes. For this reason, an adequate review of this evidence is essential in order to establish scientifically based strategy and achieve better outcomes for these patients who present with acute myocardial infarction. This review aims to present objectively the most recent evidence available on this topic.


Resumo O adequado manejo da doença arterial coronariana (DAC) multivascular, no contexto do infarto agudo do miocárdio com supradesnivelamento do segmento ST e da intervenção coronariana percutânea primária, é um dos grandes motivos de controvérsia em Cardiologia. Embora as principais diretrizes mundiais não recomendem a revascularização completa de forma rotineira nesses pacientes, recentes ensaios clínicos randomizados (ECRs) têm demonstrado benefício dessa abordagem na redução de desfechos cardiovasculares. Por esse motivo, torna-se imprescindível uma adequada revisão dessas evidências, a fim de que se possa estabelecer uma conduta cientificamente embasada e capaz de trazer benefícios aos pacientes que se apresentam no contexto agudo do infarto do miocárdio. Esta revisão objetivou apresentar de forma objetiva as evidências mais recentes disponíveis a respeito desse tema.

17.
Arq Bras Cardiol ; 109(6): 599-605, 2017 Dec.
Artigo em Inglês, Português | MEDLINE | ID: mdl-29185617

RESUMO

The best approach of multivessel coronary artery disease in the context of acute myocardial infarction with ST segment elevation and primary percutaneous coronary intervention is one of the main reasons for controversy in cardiology. Although the main global guidelines do not recommend routine complete revascularization in these patients, recent randomized clinical trials have demonstrated benefit of this approach in reducing cardiovascular outcomes. For this reason, an adequate review of this evidence is essential in order to establish scientifically based strategy and achieve better outcomes for these patients who present with acute myocardial infarction. This review aims to present objectively the most recent evidence available on this topic.


Assuntos
Doença da Artéria Coronariana/cirurgia , Intervenção Coronária Percutânea/métodos , Infarto do Miocárdio com Supradesnível do Segmento ST/cirurgia , Doença da Artéria Coronariana/mortalidade , Humanos , Revascularização Miocárdica , Infarto do Miocárdio com Supradesnível do Segmento ST/mortalidade
18.
JAMA Oncol ; 3(12): e173290, 2017 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-29049607

RESUMO

Importance: Cytotoxic CD8+ tumor-infiltrating lymphocytes (TILs) participate in immune control of epithelial ovarian cancer; however, little is known about prognostic patterns of CD8+ TILs by histotype and in relation to other clinical factors. Objective: To define the prognostic role of CD8+ TILs in epithelial ovarian cancer. Design, Setting, and Participants: This was a multicenter observational, prospective survival cohort study of the Ovarian Tumor Tissue Analysis Consortium. More than 5500 patients, including 3196 with high-grade serous ovarian carcinomas (HGSOCs), were followed prospectively for over 24 650 person-years. Exposures: Following immunohistochemical analysis, CD8+ TILs were identified within the epithelial components of tumor islets. Patients were grouped based on the estimated number of CD8+ TILs per high-powered field: negative (none), low (1-2), moderate (3-19), and high (≥20). CD8+ TILs in a subset of patients were also assessed in a quantitative, uncategorized manner, and the functional form of associations with survival was assessed using penalized B-splines. Main Outcomes and Measures: Overall survival time. Results: The final sample included 5577 women; mean age at diagnosis was 58.4 years (median, 58.2 years). Among the 5 major invasive histotypes, HGSOCs showed the most infiltration. CD8+ TILs in HGSOCs were significantly associated with longer overall survival; median survival was 2.8 years for patients with no CD8+ TILs and 3.0 years, 3.8 years, and 5.1 years for patients with low, moderate, or high levels of CD8+ TILs, respectively (P value for trend = 4.2 × 10−16). A survival benefit was also observed among women with endometrioid and mucinous carcinomas, but not for those with the other histotypes. Among HGSOCs, CD8+ TILs were favorable regardless of extent of residual disease following cytoreduction, known standard treatment, and germline BRCA1 pathogenic mutation, but were not prognostic for BRCA2 mutation carriers. Evaluation of uncategorized CD8+ TIL counts showed a near-log-linear functional form. Conclusions and Relevance: This study demonstrates the histotype-specific nature of immune infiltration and provides definitive evidence for a dose-response relationship between CD8+ TILs and HGSOC survival. That the extent of infiltration is prognostic, not merely its presence or absence, suggests that understanding factors that drive infiltration will be the key to unraveling outcome heterogeneity in this cancer.

19.
Rev. peru. med. exp. salud publica ; 34(3): 436-444, jul.-sep. 2017. graf
Artigo em Espanhol | LILACS-Express | ID: biblio-902940

RESUMO

RESUMEN Objetivos Evaluar el efecto de las nanopartículas de ZnO, TiO2 y SiO2 sobre la viabilidad celular y la expresión génica de las interleuquinas 7 y 3 y del factor estimulante de colonias de granulocito - macrófago (GM-CSF) en Mus musculus. Materiales y métodos Se extrajo médula ósea roja de cinco roedores (Balb/c) para el estudio de viabilidad celular mediante la prueba de MTT. Por otro lado, grupos cinco roedores fueron inoculados vía intraperitoneal con dosis de 0,5; 1; 2,5; 5 y 10 mg/kg de nanopartículas de ZnO y SiO2 y de 5; 10; 15; 20 y 25 mg/kg de nanopartículas de TiO2, 30 h después, se obtuvo el ARN a partir de la médula ósea roja para los análisis de expresión génica empleando las técnicas de PCR y RT-PCR cuantitativa. Resultados Las nanopartículas de ZnO y SiO2 redujeron la viabilidad celular de una manera dosis-dependiente en un 37 y 26%, respectivamente, a partir de una dosis de 1 mg/kg. En cuanto al efecto sobre la expresión génica, a las dosis 5 y 10 mg/kg, las nanopartículas de TiO2 redujeron en mayor porcentaje la expresión de las interleuquinas 7 y 3 (55,3 y 70,2% respectivamente), con respecto a la expresión del GM-CSF, el mayor porcentaje de reducción lo produjo las nanopartículas de SiO2 (91%). Las nanopartículas de ZnO redujeron a partir de las dosis de 20 y 25 mg/kg. Conclusiones Las nanopartículas de ZnO, SiO2 y TiO2 alteran la viabilidad celular y la expresión génica en la médula ósea de ratón.


ABSTRACT Objectives To evaluate the effect of ZnO, TiO2 and SiO2 nanoparticles on cell viability and expression of the interleukin 7, interleukin 3, and granulocyte-macrophage colony stimulating factor (GM-CSF) genes in Mus musculus. Material and methods Red bone marrow was extracted from five Balb/c mice for the analysis of cell viability using the MTT test. The mice were divided into two groups of five each: one group was inoculated intraperitoneally with 0.5, 1.0, 2.5, 5.0, and 10 mg/kg of ZnO and SiO2 nanoparticles, respectively, and the other group was inoculated with 5.0, 10.0, 15.0, 20.0, and 25 mg/kg of TiO2 nanoparticles, respectively. Thirty hours later, RNA was extracted from the red bone marrow of the mice in both groups for gene expression analysis using quantitative PCR and RT-PCR. Results ZnO and SiO2 nanoparticles reduced cell viability in a dose-dependent manner by 37% and 26%, respectively, starting at a dose of 1 mg/kg. TiO2 nanoparticles at 5 mg/kg and 10 mg/kg reduced the gene expression of interleukins 7 and 3 by 55.3% and 70.2%, respectively, and SiO2 nanoparticles caused the greatest decrease (91%) in the expression of GM-CSF. ZnO nanoparticles reduced the expression of GM-CSF starting at doses of 20 mg/kg and 25 mg/kg. Conclusions ZnO, SiO2 and TiO2 nanoparticles affect cell viability and gene expression in the mouse bone marrow.

20.
Br J Cancer ; 117(7): 1048-1062, 2017 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-28829762

RESUMO

BACKGROUND: Despite a high prevalence of deleterious missense variants, most studies of RAD51C ovarian cancer susceptibility gene only provide in silico pathogenicity predictions of missense changes. We identified a novel deleterious RAD51C missense variant (p.Arg312Trp) in a high-risk family, and propose a criteria to prioritise RAD51C missense changes qualifying for functional analysis. METHODS: To evaluate pathogenicity of p.Arg312Trp variant we used sequence homology, loss of heterozygosity (LOH) and segregation analysis, and a comprehensive functional characterisation. To define a functional-analysis prioritisation criteria, we used outputs for the known functionally confirmed deleterious and benign RAD51C missense changes from nine pathogenicity prediction algorithms. RESULTS: The p.Arg312Trp variant failed to correct mitomycin and olaparib hypersensitivity and to complement abnormal RAD51C foci formation according to functional assays, which altogether with LOH and segregation data demonstrated deleteriousness. Prioritisation criteria were based on the number of predictors providing a deleterious output, with a minimum of 5 to qualify for testing and a PredictProtein score greater than 33 to assign high-priority indication. CONCLUSIONS: Our study points to a non-negligible number of RAD51C missense variants likely to impair protein function, provides a guideline to prioritise and encourage their selection for functional analysis and anticipates that reference laboratories should have available resources to conduct such assays.


Assuntos
Neoplasias da Mama/genética , Carcinoma/genética , Neoplasias Colorretais/genética , Proteínas de Ligação a DNA/genética , Neoplasias Ovarianas/genética , Neoplasias Gástricas/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Estudos de Casos e Controles , Ciclo Celular/efeitos dos fármacos , Ciclo Celular/genética , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Células Cultivadas , Instabilidade Cromossômica , Análise Mutacional de DNA , Exoma , Feminino , Predisposição Genética para Doença , Genótipo , Histonas/metabolismo , Humanos , Perda de Heterozigosidade , Masculino , Pessoa de Meia-Idade , Mitomicina/farmacologia , Mutação de Sentido Incorreto , Linhagem , Medição de Risco/métodos , Homologia de Sequência
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