Chiara Colombo

Feasibility of a new generation three-dimensional echocardiography for right ventricular volumetric and functional measurements.

Right ventricular (RV) dimensions and function are of diagnostic and prognostic importance in cardiac disease. Because of the peculiar morphology of the right ventricle, 2-dimensional echocardiography has several limitations in RV evaluation. Recently, new 3-dimensional transthoracic echocardiographic software adapted for RV morphology was introduced. The aims of this study were to evaluate the feasibility of 3-dimensional RV analysis in a large population and to compare and correlate 3-dimensional RV data with classic 2-dimensional and Doppler parameters, including tricuspid annular plane systolic excursion and peak systolic velocity on Doppler tissue imaging, RV fractional shortening area, RV stroke volume (by the Doppler method), and pulmonary arterial systolic pressure. Two hundred subjects were studied: 48 normal controls and 152 patients with valvular heart disease (104 patients), idiopathic dilated cardiomyopathy (20 patients), or pulmonary hypertension (28 patients). The mean times for 3-dimensional acquisition and 3-dimensional reconstruction were 3 +/- 1 and 4 +/- 2 minutes, respectively. Imaging quality was good in most cases (85%). The mean RV diastolic and systolic volumes were 103 +/- 38 and 46 +/- 28 ml, respectively. The RV ejection fraction (RVEF) was correlated negatively with pulmonary arterial systolic pressure and positively with tricuspid annular plane systolic excursion, peak systolic velocity, and fractional shortening area. The pathologic group was characterized by larger RV volumes and lower RVEFs. Three-dimensional echocardiography clearly showed that in the pathologic group, patients with pulmonary hypertension had the largest RV volumes and the lowest RVEFs and that those with idiopathic dilated cardiomyopathy were characterized by RVEFs lower than those of patients with valvular disease. In conclusion, this new quantitative 3-dimensional method to assess RV volumes and function is feasible, relatively simple, and not time consuming. Data obtained with 3-dimensional analysis are well correlated with those obtained by 2-dimensional and Doppler methods and can differentiate normal and pathologic subjects.

PERMANENT ATRIAL FIBRILLATION AFFECTS EXERCISE CAPACITY IN CHRONIC HEART FAILURE PATIENTS.

AIMS The influence of permanent atrial fibrillation on exercise tolerance and cardio-respiratory function during exercise in heart failure (HF) is unknown. METHODS AND RESULTS We retrospectively compared the results of 942 cardiopulmonary exercise tests, performed consecutively at seven Italian laboratories, in HF patients with atrial fibrillation (n = 180) and sinus rhythm (n = 762). By multivariable logistic regression analysis, peak VO(2) (OR 0.376, 95% CI 0.240-0.588, P < 0.0001), O(2)pulse (VO(2)/heart rate, HR) (OR 0.236, 95% CI 0.152-0.366, P < 0.0001), VCO(2) (OR 3.97, 95% CI 2.163-7.287, P < 0.0001), and ventilation (OR 1.38, 95% CI 1.045-1.821, P = 0.0231) were independently associated with atrial fibrillation. Anaerobic threshold (AT) was identified in 132 of 180 (73%) atrial fibrillation and in 649 of 762 (85%) sinus rhythm patients (P = 0.0002). By multivariable logistic regression analysis, only peak VO(2) (OR 0.214, 95% CI 0.155-0.296, P < 0.0001) was independently associated with unidentified AT. At AT, atrial fibrillation HF patients had higher HR (P < 0.0001) and higher VO(2) (P < 0.001) compared with sinus rhythm HF patients. Among AT variables, by multivariable logistic regression analysis, only HR was an independent predictor of atrial fibrillation. CONCLUSION In HF patients with permanent atrial fibrillation, exercise performance is reduced as reflected by reduced peak VO(2). The finding of unidentified AT is associated with a poor performance. In atrial fibrillation patients, VO(2) is higher at AT whereas lower at peak. This last observation raises uncertainties about the use of AT data to define performance and prognosis of HF patients with atrial fibrillation.

Psychological Well-Being, Family Relations, and Developmental Issues of Children Left Behind

The phrase “children left behind” refers to minors who are left in their home country while one or both of their parents emigrate for work for at least six months. From a quantitative point of view, children left behind in countries with strong migratory pressure are many. Separation of families in migration is tied to implications about well-being of the people involved—mainly the children—and of the communities to which they belong. The emotional neglect felt by these children is associated with lack of affection and physical intimacy. Through a review of the literature, the purpose of this paper was to show that distress in this pattern of deprivation is manifested by the children in several ways and in different contexts: low school performance, drop-out from school, conflicts with teachers and peers, anxiety, low self-esteem, tendency to feel depressed, apathy, suicidal behaviour, and substance abuse.

Resection is responsible for loss of transcription around a double-strand break in Saccharomyces cerevisiae

Emerging evidence indicate that the mammalian checkpoint kinase ATM induces transcriptional silencing in cis to DNA double-strand breaks (DSBs) through a poorly understood mechanism. Here we show that in Saccharomyces cerevisiae a single DSB causes transcriptional inhibition of proximal genes independently of Tel1/ATM and Mec1/ATR. Since the DSB ends undergo nucleolytic degradation (resection) of their 5′-ending strands, we investigated the contribution of resection in this DSB-induced transcriptional inhibition. We discovered that resection-defective mutants fail to stop transcription around a DSB, and the extent of this failure correlates with the severity of the resection defect. Furthermore, Rad9 and generation of γH2A reduce this DSB-induced transcriptional inhibition by counteracting DSB resection. Therefore, the conversion of the DSB ends from double-stranded to single-stranded DNA, which is necessary to initiate DSB repair by homologous recombination, is responsible for loss of transcription around a DSB in S. cerevisiae. DOI: http://dx.doi.org/10.7554/eLife.08942.001

The RNA binding protein Npl3 promotes resection of DNA double-strand breaks by regulating the levels of Exo1.

Abstract Eukaryotic cells preserve genome integrity upon DNA damage by activating a signaling network that promotes DNA repair and controls cell cycle progression. One of the most severe DNA damage is the DNA double-strand break (DSB), whose 5΄ ends can be nucleolitically resected by multiple nucleases to create 3΄-ended single-stranded DNA tails that trigger DSB repair by homologous recombination. Here, we identify the Saccharomyces cerevisiae RNA binding protein Npl3 as a new player in DSB resection. Npl3 is related to both the metazoan serine-arginine-rich and the heterogeneous nuclear ribonucleo-proteins. NPL3 deletion impairs the generation of long ssDNA tails at the DSB ends, whereas it does not exacerbate the resection defect of exo1Δ cells. Furthermore, either the lack of Npl3 or the inactivation of its RNA-binding domains causes decrease of the exonuclease Exo1 protein levels as well as generation of unusual and extended EXO1 RNA species. These findings, together with the observation that EXO1 overexpression partially suppresses the resection defect of npl3Δ cells, indicate that Npl3 participates in DSB resection by promoting the proper biogenesis of EXO1 mRNA.

Three-dimensional echocardiography in valve disease.

This review covers the role of three-dimensional (3D) echocardiography in the diagnosis of heart valve disease. Several factors have contributed to the evolution of this technique, which is currently a simple and routine method: rapid evolution in probe and computer technologies, demonstration that 3D data sets allowed more complete and accurate evaluation of cardiac structures, emerging clinical experience indicating the strong potential particularly in valve diseases, volume and function of the two ventricle measurements and several other fields. This report will review current and future applications of 3D echocardiography in mitral, aortic and tricuspid valve diseases underlying both qualitative (morphologic) and quantitative advantages of this technique.