Bidirectional transcription initiation marks accessible chromatin and is not specific to enhancers

Abstract Background Enhancers are modular regulatory elements that are central to the spatial and temporal regulation of gene expression. Bidirectional transcription initiating at enhancers has been proposed to mark active enhancers and as such has been utilized to experimentally identify active enhancers de novo. Results Here, we show that bidirectional transcription initiation is a pervasive feature of accessible chromatin, including at enhancers, promoters, and other DNase hypersensitive regions not marked with canonical histone modification profiles. Transcription is less predictive for enhancer activity than epigenetic modifications such as H3K4me1 or the accessibility of DNA when measured both in enhancer assays and at endogenous loci. The stability of enhancer initiated transcripts does not influence measures of enhancer activity and we cannot detect evidence of purifying selection on the resulting enhancer RNAs within the human population. Conclusions Our results indicate that bidirectional transcription initiation from accessible chromatin is not sufficient for, nor specific to, enhancer activity. Transcription initiating at enhancers may be a frequent by-product of promiscuous RNA polymerase initiation at accessible chromatin and is unlikely to generally play a functional role in enhancer activity

Estudo de vigilância epidemiológica da profilaxia do tromboembolismo venoso em especialidades cirúrgicas de um hospital universitário de nível terciário Study of epidemiological surveillance of venous thromboembolism prophylaxis in surgical specialties of a school tertiary referral hospital

CONTEXTO: O tromboembolismo venoso pós-operatório é uma entidade frequente e grave, que pode levar à embolia pulmonar e à síndrome pós-trombótica. Apesar dos benefícios comprovados pela profilaxia, nota-se uma inadequação na sua indicação. OBJETIVO: Verificar a indicação de heparina profilática entre pacientes de diferentes clínicas cirúrgicas de um hospital universitário de nível terciário. MÉTODOS: Realizou-se avaliação prospectiva, através de busca ativa, por 10 dias seguidos, em cada mês, no período de setembro a dezembro de 2005, de pacientes operados nas clínicas: cirurgia geral (aparelho digestório e proctologia), ginecologia, neurocirurgia, ortopedia e traumatologia, urologia e angiologia e cirurgia vascular, com identificação dos fatores de risco para tromboembolismo venoso e o uso profilático de heparina, de acordo com as normas da Sociedade Brasileira de Angiologia e Cirurgia Vascular. RESULTADOS: Foram avaliados 357 pacientes, 24 (6,7%) classificados como de baixo risco para tromboembolismo venoso, 128 (35,9%) de risco moderado, e a maioria, 205 (57,4%) de alto risco. Do total de pacientes, 184 (51,5%) receberam heparina profilática. A heparina foi utilizada em 73,3% dos pacientes da cirurgia geral, em 16,7% da ginecologia, em 50,0% da neurologia, em 32,5% da ortopedia e traumatologia, em 37,3% da urologia e em 97,7% da clínica de angiologia e cirurgia vascular. Das clínicas avaliadas, apenas 38,3% dos pacientes de risco moderado e 64,4% dos de alto risco receberam heparina profilática. Esta foi utilizada de forma adequada em 77,6% dos pacientes de risco moderado e em 63,6% dos de alto risco. Trombocitopenia, sangramento menor e maior, foram identificados em 3 (1,6%), 12 (6,5%) e 2 (1,1%) pacientes que receberam heparina, respectivamente. Foram diagnosticados clinicamente seis (1,7%) episódios de tromboembolismo venoso. CONCLUSÃO:Apesar das indicações bem definidas da heparina na profilaxia do tromboembolismo venoso, verifica-se adesão incompleta por parte dos profissionais médicos da especialidade, expondo os pacientes a complicações graves.<br>CONTEXT: Postoperative venous thromboembolism is a frequent and severe disease that can lead to pulmonary embolism and post thrombotic syndrome. Although the venous thromboembolism prophylaxis is a proven strategy, an unsuitable indication is observed. OBJECTIVE: To verify the indication of prophylaxis with heparin among patients of several surgical specialties of a School Tertiary Referral Hospital. METHODS: It was accomplished a prospective study during 10 consecutive days in each month, from September to December of 2005, with 360 patients surgically treated in the specialties: General Surgery, Gynecology, Neurosurgery, Ortopedy and Traumatology, Urology and Angiology and Vascular Surgery, identifying risk factors for the development of venous thromboembolism (VTE) and the use of heparin prophylaxis according to the recommendations of the Brazilian Society of Angiology and Vascular Surgery. RESULTS: Three hundred and fifty seven patients were evaluated, 24 (6,7%), 128 (35,9%) and 205 (57,4%) were included in low risk, medium risk and high risk for venous thromboembolism, respectively. One hundred and eighty four patients (51,5%) of the sample received prophylactic heparin. Heparin was used in 73,3% of the patients of General Surgery, 16,7% of Gynecology, 50,0% of Neurosurgery, 32,5% of Ortopedy and Traumatology, 37,3% of Urology and 97,7% of Angiology and Vascular Surgery. Only 38,3% of medium risk and 64,4% of high risk patients received prophylactic heparin. Heparin was suitably used in 77,6% of medium risk and in 63,6% of high risk patients. Thrombocytopenia, minor bleeding and major bleeding occurred in 3 (1,6%), 12 (6,5%) and 2 (1,1%) of the patients, respectively. Thromboembolic complications occurred in 6 (1,7%) cases. CONCLUSION: Although the indications of prophylactic heparin to venous thromboembolism are well known, we verify an incomplete adhesion of medical professionals, exposing patients to severe complications

Estudos de consumo alimentar: aspectos metodológicos gerais e o seu emprego na avaliação de crianças e adolescentes Food consumption studies: general methodological aspects and its use in the evaluation of children and adolescents aged

Este artigo discute aspectos metodológicos dos estudos de consumo alimentar em crianças e adolescentes. Para compreender esses aspectos, descreve, em contexto mais amplo, a importância da Epidemiologia Nutricional no estudo descritivo da relação da dieta com o surgimento das enfermidades, bem como origem histórica, importância, vantagens, limitações e usos dos métodos empregados para medir a ingestão alimentar, especialmente em crianças e adolescentes, em estudos epidemiológicos populacionais. Apresenta ainda alguns trabalhos da literatura científica clássica e contemporânea, demonstrando os resultados obtidos e algumas sugestões para aperfeiçoamento desses métodos. Finalmente, evidencia os aspectos mais relevantes que, por consenso de vários pesquisadores, competem como fatores limitantes ou facilitadores no emprego desses métodos, conferindo a esses, maior validade e reprodutibilidade nos estudos de consumo alimentar de crianças e adolescentes.<br>This article discusses methodological aspects of food consumption studies in children and adolescents. To reach the understanding of these methods it provides the value of Nutritional Epidemiology in a general context through a descriptive study of diet relation with the manifestation of disease as well as historical origin, value, advantage, constraints and use of methods employed to measure food intake, especially in children and adolescents in population epidemiological studies. In addition, it presents classic and contemporaneous literature demonstrating results obtained and some suggestions to improve these methods. Finally, it discloses the more relevant aspects that by consensus of many researchers compete with constraining and facilitating factors in their use providing them with more validity and reproducibility concerning studies of food consumption for children and adolescents

The ‘heritability’ of domestication and its functional partitioning in the pig

We propose to estimate the proportion of variance explained by regression on genome-wide markers (or genomic heritability) when wild/domestic status is considered the phenotype of interest. This approach differs from the standard Fst in that it can accommodate genetic similarity between individuals in a general form. We apply this strategy to complete genome data from 47 wild and domestic pigs from Asia and Europe. When we partitioned the total genomic variance into components associated to subsets of single nucleotide polymorphisms (SNPs) defined in terms of their annotation, we found that potentially deleterious non-synonymous mutations (9566 SNPs) explained as much genetic variance as the whole set of 25 million SNPs. This suggests that domestication may have affected protein sequence to a larger extent than regulatory or other kinds of mutations. A pathway-guided analysis revealed ovarian steroidogenesis and leptin signaling as highly relevant in domestication. The genomic regression approach proposed in this study revealed molecular processes not apparent through typical differentiation statistics. We propose that at least some of these processes are likely new discoveries because domestication is a dynamic process of genetic selection, which may not be completely characterized by a static metric like Fst. Nevertheless, and despite some particularly influential mutation types or pathways, our analyses tend to rule out a simplistic genetic basis for the domestication process: neither a single pathway nor a unique set of SNPs can explain the process as a whole.This work was developed whereas the senior author was visiting CSIRO Agriculture in St Lucia campus (Brisbane, Australia) funded by a CSIRO McMaster Visiting Fellowship. Work also funded by AGL2013-41834-R grants (Ministry of Economy and Science, Spain) to MPE and NIH grant R01GM101219 (USA) to GDLC.Peer reviewe

Adapting the brief coping cat for children with anxiety to a group setting in the spanish public mental health system: a hybrid effectiveness-implementation pilot study

Group therapy may offer a promising solution to reducing patient waiting lists for publicly funded mental health services. In this study, an individual brief cognitive behavioral therapy (BCBT) intervention was adapted for implementation in a group setting in the Spanish public mental health care system. The study was designed to test initial clinical effectiveness, acceptability, and feasibility of the group adaptation of BCBT for child anxiety. The study utilized an uncontrolled multiple-group design for 8 weeks (1 h per week). Inclusion criteria were (i) children and young adolescents between 8 and 15 years old, and (ii) a clinical diagnosis of general anxiety disorder, social phobia, and/or separation anxiety disorder. Five groups were completed (n = 33; mean age = 11 years; 42.4% females). A total of 31 (93.9%) participants completed at least 7 sessions, and follow-up data were collected for 84.9% (n = 28) of participants. Overall, anxiety symptoms were reduced after intervention on the Spence Children Anxiety Scale, Generalized Anxiety Disorder Questionnaire-IV, Social Anxiety Scale for Children-Revised, and Separation Anxiety Symptom Inventory. Our findings suggest that group BCBT was associated with beneficial treatment outcomes, was acceptable and feasible for children with anxiety in the Spanish public mental health system. Both participants and their caregivers reported satisfaction and feelings of safety with the intervention. Results underscore the need for a larger-scale hybrid effectiveness-implementation trial of BCBT in a group setting throughout more community mental health centers in different Spanish states. Such work could improve patient access to and benefit from an evidence-based treatment that works in community settings