Heart failure in adult congenital heart disease: tetralogy of Fallot.

The number of rTOF patients who survive into adulthood is steadily rising, with currently more than 90% reaching the third decade of life. However, rTOF patients are not cured, but rather have a lifelong increased risk for cardiac and non-cardiac complications. Heart failure is recognized as a significant complication. Its occurrence is strongly associated with adverse outcome. Unfortunately, conventional concepts of heart failure may not be directly applicable in this patient group. This article presents a review of the current knowledge on HF in rTOF patients, including incidence and prevalence, the most common mechanisms of heart failure, i.e., valvular pathologies, shunt lesions, left atrial hypertension, primary left heart and right heart failure, arrhythmias, and coronary artery disease. In addition, we will review information regarding extracardiac complications, risk factors for the development of heart failure, clinical impact and prognosis, and assessment possibilities, particularly of the right ventricle, as well as management strategies. We explore potential future concepts that may stimulate further research into this field.

The sleep-feeding conflict: Understanding behavioral integration through genetic analysis in Drosophila.

One of the brain's most important functions is the control of homeostatically regulated behaviors. Dysregulation of the neural systems controlling sleep and feeding underlies many chronic illnesses. In a recent study published in Current Biology we showed that flies, like mammals, suppress sleep when starved and identified the genes Clock and cycle as regulators of sleep during starvation. Here we show that starvation specifically disrupts sleep initiation without affecting sleep consolidation. The identification of genes regulating sleep-feeding interactions will provide insight into how the brain integrates and controls the expression of complex behaviors.

Clock and cycle limit starvation-induced sleep loss in Drosophila.

Neural systems controlling the vital functions of sleep and feeding in mammals are tightly interconnected: sleep deprivation promotes feeding, whereas starvation suppresses sleep. Here we show that starvation in Drosophila potently suppresses sleep, suggesting that these two homeostatically regulated behaviors are also integrated in flies. The sleep-suppressing effect of starvation is independent of the mushroom bodies, a previously identified sleep locus in the fly brain, and therefore is regulated by distinct neural circuitry. The circadian clock genes Clock (Clk) and cycle (cyc) are critical for proper sleep suppression during starvation. However, the sleep suppression is independent of light cues and of circadian rhythms as shown by the fact that starved period mutants sleep like wild-type flies. By selectively targeting subpopulations of Clk-expressing neurons, we localize the observed sleep phenotype to the dorsally located circadian neurons. These findings show that Clk and cyc act during starvation to modulate the conflict of whether flies sleep or search for food.

Extracting gene pathway relations using a hybrid grammar: the Arizona Relation Parser.

MOTIVATION: Text-mining research in the biomedical domain has been motivated by the rapid growth of new research findings. Improving the accessibility of findings has potential to speed hypothesis generation. RESULTS: We present the Arizona Relation Parser that differs from other parsers in its use of a broad coverage syntax-semantic hybrid grammar. While syntax grammars have generally been tested over more documents, semantic grammars have outperformed them in precision and recall. We combined access to syntax and semantic information from a single grammar. The parser was trained using 40 PubMed abstracts and then tested using 100 unseen abstracts, half for precision and half for recall. Expert evaluation showed that the parser extracted biologically relevant relations with 89% precision. Recall of expert identified relations with semantic filtering was 35 and 61% before semantic filtering. Such results approach the higher-performing semantic parsers. However, the AZ parser was tested over a greater variety of writing styles and semantic content. AVAILABILITY: Relations extracted from over 600 000 PubMed abstracts are available for retrieval and visualization at http://econport.arizona.edu:8080/NetVis/index.html.