European study of ambulatory management of heart failure by cardiologists

INTRODUCTION AND OBJECTIVES: This cross-sectional study examined the overall clinical characteristics and management of 1252 outpatients with heart failure in 3 countries (Spain, France and Germany). MATERIAL AND METHOD: A standardized questionnaire was used to record demographic, diagnostic, clinical and treatment data for all patients seen on one day (26 April 2001) by 465 outpatient cardiologists. RESULTS: Men accounted for 62.1% of the patients in the population, and mean age of the patients was 68.3 years. In the twelve months prior to the study 78% of the patients consulted their physician at least once because of heart failure, and 36.2% had hospital admissions. Differences between the three countries were observed in reported causes of heart failure (alone or in combination) such as ischemic heart disease (France 40.7%, Germany 41.3%, Spain 26%, P<.0001) and hypertension (France 10.7%, Germany 16.7%, Spain 43.6%, P<.0001). How-ever the proportion of patients with prior myocardial infarction was very similar (France 63.7%, Germany 69.5%, Spain 65%, P=NS). Diuretics were not prescribed in 19.7% of the patients, ACE inhibitors were not prescribed in 27.9%, and beta blockers were not prescribed in 52.3%. CONCLUSIONS: The study provides further information on the consumption of large amounts of medical resources because of heart failure. The reported etiologies differed between countries. However, the proportion of patients with prior myocardial infarction was very similar. Treatment with ACE inhibitors and beta blockers was slightly more common than previously reported, although beta blockers continue to be underused.     

Composition of the HLA‐DR‐associated human thymus peptidome

Major histocompatibility complex class II (MHC‐II) molecules bind to and display antigenic peptides on the surface of antigen‐presenting cells (APCs). In the absence of infection, MHC‐II molecules on APCs present self‐peptides and interact with CD4⁺ T cells to maintain tolerance and homeostasis. In the thymus, self‐peptides bind to MHC‐II molecules expressed by defined populations of APCs specialised for the different steps of T‐cell selection. Cortical epithelial cells present peptides for positive selection, whereas medullary epithelial cells and dendritic cells are responsible for peptide presentation for negative selection. However, few data are available on the peptides presented by MHC molecules in the thymus. Here, we apply mass spectrometry to analyse and identify MHC‐II‐associated peptides from five fresh human thymus samples. The data show a diverse self‐peptide repertoire, mostly consisting of predicted MHC‐II high binders. Despite technical limitations preventing single cell population analyses of peptides, these data constitute the first direct assessment of the HLA‐II‐bound peptidome and provide insight into how this peptidome is generated and how it drives T‐cell repertoire formation.     

Learning‐induced modulations of the stimulus‐preceding negativity

The neural basis of feedback expectation, which is crucial in learning theory, has only been minimally studied. Stimulus‐preceding negativity (SPN), an ERP component that appears prior to the presentation of feedback, has been proposed as being related to feedback expectation. The present study showed, for the first time, amplitude modulations of the SPN component during learning acquisition in a trial‐by‐trial associative learning task. The results indicate that SPN could be a plausible electrophysiological index of the cognitive processes engaged while expecting the appearance of relevant feedback during reinforcement learning.     

Influence of maturational status in the exercise-induced release of cardiac troponin T in healthy young swimmers

ObjectivesTo determine the influence of maturational status on the release of cardiac troponin T (cTnT) induced by a bout of 30 min, high-intensity, continuous exercise.DesignQuasi-experimental, cross-sectional study.MethodsSeventy male, young, well trained swimmers (age range 7–18 years, training experience 1–11 years) were classified by maturational stages: Tanner stage I (n = 14), II (n = 15), III (n = 15), IV (n = 13), and V (n = 13). Participants underwent a distance-trial of 30 min continuous swimming, and cTnT was measured before, immediately after and 3 h after exercise. Changes in cTnT over time were compared among groups, and associated with exercise load.ResultsBasal cTnT was higher in Tanner-V (3.8–8.1 ng/L) compared with I (1.5–5.5 ng/L, p < 0.001), II (1.5–4.5 ng/L, p < 0.001) and III (1.5–6.8 ng/L, p = 0.003), and in IV (1.5–6.3 ng/L) compared with II (p = 0.036). Maximal elevations of cTnT from baseline were notable (p < 0.001) and comparable among maturational stages (p = 0.078). The upper reference limit for myocardial injury was exceeded in 35.7% of the participants, without differences among groups (p = 0.18). Baseline cTnT correlated with participant characteristics, and maximal cTnT elevations from baseline with exercise internal load (%HRpeak, r_s = 0.34, p =  0.003; %HRmean, r_s = 0.28, p = 0.02).ConclusionsMaturational status influences positively absolute pre- and post-exercise cTnT but not its elevation after a bout of 30 min, high-intensity, continuous exercise.     

New Insights on the Self‐Organization of PEG/α‐Cyclodextrin‐Based Polyrotaxanes in Solution: An Experimental and Theoretical Study

Size exclusion chromatography coupled with light scattering (SEC/MALS), dynamic light scattering (DLS), steady‐state and time‐resolved fluorescence, as well as molecular dynamics (MD) simulations are used to study the behavior of several poly(ethylene glycol) (PEG)/α‐cyclodextrins (αCDs) polyrotaxanes (PRs) in solution. The number of CD units in any of the PRs studied is always smaller than that required to saturate the PEG chains. These PRs seem to aggregate in dimethyl sulfoxide (DMSO) solution. The presence of hairpins in the non‐saturated PRs contributes to diminishing their expected large dimensions. Intra‐ and inter­molecular interactions and forces responsible for hairpins and aggregation are investigated.

     

Prognostic value of cytokines and neurohormones in severe heart failure

BACKGROUND AND OBJECTIVES: The screening of candidates for heart transplantation continues to present difficulties. High plasma levels of cytokines and neurohormones have been associated with a poor prognosis in heart failure but their usefulness for identifying candidates for heart transplantation is still not established. METHODS: In 83 patients (59 11 years old), with systolic left ventricular dysfunction and New York Heart Association functional class III-IV, we assessed levels of aldosterone, atrial natriuretic peptide, plasma renin activity, angiotensin II, norepinephrine, endothelin, interleukin-6 and tumor necrosis factor-alpha. RESULTS: Over the following year, 13 patients died and 26 received heart transplantation. Mean ejection fraction was 23 6%, end-diastolic and end-systolic diameters were 73 10 and 60 10 mm, respectively. Univariate analysis identified the following variables to be associated with poor prognosis: angiotensin II (p = 0.001), norepinephrine (p = 0.003), plasma renin activity (p = 0.02), systolic blood pressure (p = 0.006), end-diastolic diameter (p = 0.02) and end-systolic diameter (p = 0.04). Multivariate regression analysis identified the following variables to be independent predictors of death or need for heart transplantation: a low cardiac index (p = 0.007), plasma angiotensin II (p = 0.001) and pulmonary capillary wedge pressure (p = 0.04) The sensitivity and specificity of angiotensin II for predicting poor outcome was only moderate according to interpretation of the receiver operating curves. CONCLUSIONS: Although plasma angiotensin II was the best neurohormone for identifying patients with severe heart failure and the worst prognosis, its sensitivity and specificity for predicting death or the need for heart transplantation was limited. The decision to transplant should continue to be based on clinical and hemodynamic parameters.     

High-cost, high-capacity backbone for global brain communication

Network studies of human brain structural connectivity have identified a specific set of brain regions that are both highly connected and highly central. Recent analyses have shown that these putative hub regions are mutually and densely interconnected, forming a "rich club" within the human brain. Here we show that the set of pathways linking rich club regions forms a central high-cost, high-capacity backbone for global brain communication. Diffusion tensor imaging (DTI) data of two sets of 40 healthy subjects were used to map structural brain networks. The contributions to network cost and communication capacity of global cortico-cortical connections were assessed through measures of their topology and spatial embedding. Rich club connections were found to be more costly than predicted by their density alone and accounted for 40% of the total communication cost. Furthermore, 69% of all minimally short paths between node pairs were found to travel through the rich club and a large proportion of these communication paths consisted of ordered sequences of edges ("path motifs") that first fed into, then traversed, and finally exited the rich club, while passing through nodes of increasing and then decreasing degree. The prevalence of short paths that follow such ordered degree sequences suggests that neural communication might take advantage of strategies for dynamic routing of information between brain regions, with an important role for a highly central rich club. Taken together, our results show that rich club connections make an important contribution to interregional signal traffic, forming a central high-cost, high-capacity backbone for global brain communication.     

High-risk cytogenetics and persistent minimal residual disease by multiparameter flow cytometry predict unsustained complete response after autologous stem cell transplantation in multiple myeloma

The achievement of complete response (CR) after high-dose therapy/autologous stem cell transplantation (HDT/ASCT) is a surrogate for prolonged survival in multiple myeloma; however, patients who lose their CR status within 1 year of HDT/ASCT (unsustained CR) have poor prognosis. Thus, the identification of these patients is highly relevant. Here, we investigate which prognostic markers can predict unsustained CR in a series of 241 patients in CR at day +100 after HDT/ASCT who were enrolled in the Spanish GEM2000 (n = 140) and GEM2005 < 65y (n = 101) trials. Twenty-nine (12%) of the 241 patients showed unsustained CR and a dismal outcome (median overall survival 39 months). The presence of baseline high-risk cytogenetics by FISH (hazard ratio 17.3; P = .002) and persistent minimal residual disease by multiparameter flow cytometry at day +100 after HDT/ASCT (hazard ratio 8.0; P = .005) were the only independent factors that predicted unsustained CR. Thus, these 2 parameters may help to identify patients in CR at risk of early progression after HDT/ASCT in whom novel treatments should be investigated.