Abstract: This study evaluates adherence to guidelines by heart failure clinicians (HFCs) vs general cardiologists (GCs) for use of implantable cardioverter-defibrillators (ICDs), biventricular pacing devices (cardiac resynchronization therapy; CRT), and use of medications for heart failure (HF). The authors reviewed 563 patients with HF and an ejection fraction <or=35% for adherence to the 2005 American College of Cardiology/American Heart Association HF guidelines for the use of ICDs, CRT, and medications. There were 324 HFC and 239 GC patients. CRT guidelines were appropriately followed in 86% of HFC and 81% of GC patients (P=NS). For primary arrhythmia prevention, an ICD was implanted in 107 (42%) HFC and 50 (25%) GC patients (P<.004). Guidelines were appropriately followed in 77% of HFC and 74% of GC patients (P=NS). For medications, dose intensity of diuretics, beta-blockers, and angiotensin-converting enzyme inhibitors was significantly greater in HFC than GC patients. Guideline-recommended beta-blockers were more frequently utilized by HFCs (97%) than GCs (82%). In conclusion, HFCs and GCs appropriately follow guidelines in the majority of cases, but HFCs use appropriate medications at higher dose intensity.

Abstract: Byline: James Bonaiuto (1), Michael A. Arbib (1) Keywords: Action selection; Mirror system; Reinforcement learning; Unintended actions; Motor reorganization; Competitive queuing Abstract: A mirror system is active both when an animal executes a class of actions (self-actions) and when it sees another execute an action of that class. Much attention has been given to the possible roles of mirror systems in responding to the actions of others but there has been little attention paid to their role in self-actions. In the companion article (Bonaiuto et al. Biol Cybern 96:9--38, 2007) we presented MNS2, an extension of the Mirror Neuron System model of the monkey mirror system trained to recognize the external appearance of its own actions as a basis for recognizing the actions of other animals when they perform similar actions. Here we further extend the study of the mirror system by introducing the novel hypotheses that a mirror system may additionally help in monitoring the success of a self-action and may also be activated by recognition of one’s own apparent actions as well as efference copy from one’s intended actions. The framework for this computational demonstration is a model of action sequencing, called augmented competitive queuing, in which action choice is based on the desirability of executable actions. We show how this “what did I just do?” function of mirror neurons can contribute to the learning of both executability and desirability which in certain cases supports rapid reorganization of motor programs in the face of disruptions. Author Affiliation: (1) University of Southern California, Hedco Neuroscience Building, 120E, Room 10B, Mailing Code 2520, 3641 Watt Way, Los Angeles, CA, 90089-2520, USA Article History: Registration Date: 09/02/2010 Received Date: 17/11/2009 Accepted Date: 09/02/2010 Online Date: 09/03/2010 Article note: Electronic supplementary material The online version of this article (doi: 10.1007/s00422-010-0371-0) contains supplementary material, which is available to authorized users.

Abstract: Anaplastic thyroid carcinoma (ATC) is considered one of the most aggressive malignancies, having a poor prognosis and being refractory to conventional chemotherapy and radiotherapy. Alteration in histone deacetylase (HDAC) activity has been reported in cancer, thus encouraging the development of HDAC inhibitors, whose antitumor action has been shown in both solid and hematological malignancies. However, the molecular basis for their tumor selectivity is unknown. To find an innovative therapy for the treatment of ATCs, we studied the effects of deacetylase inhibitors on thyroid tumorigenesis models. We show that HDACs 1 and 2 are overexpressed in ATCs compared with normal cells or benign tumors and that HDAC inhibitors induce apoptosis selectively in the fully transformed thyroid cells. Our results indicate that these phenomena are mediated by a novel action of HDAC inhibitors that reduces tumor necrosis factor-related apoptosis-inducing ligand protein degradation by affecting the ubiquitin-dependent pathway. Indeed, the combined treatment with HDAC and proteasome inhibitors results in synergistic apoptosis. These results strongly encourage the preclinical application of the combination deacetylase-proteasome inhibitors for the treatment of ATC.

Abstract: Anaplastic thyroid carcinoma (ATC) is considered one of the most aggressive malignancies, having a poor prognosis and being refractory to conventional chemotherapy and radiotherapy. Alteration in histone deacetylase (HDAC) activity has been reported in cancer, thus encouraging the development of HDAC inhibitors, whose antitumor action has been shown in both solid and hematological malignancies. However, the molecular basis for their tumor selectivity is unknown. To find an innovative therapy for the treatment of ATCs, we studied the effects of deacetylase inhibitors on thyroid tumorigenesis models. We show that HDACs 1 and 2 are overexpressed in ATCs compared with normal cells or benign tumors and that HDAC inhibitors induce apoptosis selectively in the fully transformed thyroid cells. Our results indicate that these phenomena are mediated by a novel action of HDAC inhibitors that reduces tumor necrosis factor-related apoptosis-inducing ligand protein degradation by affecting the ubiquitin-dependent pathway. Indeed, the combined treatment with HDAC and proteasome inhibitors results in synergistic apoptosis. These results strongly encourage the preclinical application of the combination deacetylase-proteasome inhibitors for the treatment of ATC.

Abstract: Aims International and national consensus guidelines define appropriate indications for implantable cardioverter-defibrillators (ICDs), but the variability in implant rates in 'real world' clinical practice is still unknown. Methods and results In Emilia-Romagna, an Italian region with around 4.3 million inhabitants, a web-based registry was instituted to collect data for all ICDs implanted. Between January 2006 and December 2008, data from all consecutive patients resident in this region who underwent first implant of an ICD or a biventricular ICD were collected and standardized, considering each regional area (i.e. each of the nine provinces). The overall number of implanted ICDs had an increase in years 2007 and 2008, with a relative increase in comparison to 2006, by 14 and 48% respectively, reaching an average value of 16.2 per 100 000 inhabitants in 2008. Most of the increase was due to a rise in ICDs for primary prevention. The ratio between the implant rates of the provinces with the highest and the lowest implant rates, respectively, was around 2 in 2008. Conclusion Implant rates for ICDs, considering both primary and secondary prevention of sudden death, show up to two-fold variations even in a geographical region where the general level of health care is advanced and well appreciated by the population. The lack of a common strategy for sudden death prevention, approved by both physicians and institutional regional authorities, together with some degree of variability in translating guidelines into clinical practice, were identified as the main factors explaining the heterogeneity in ICD implant rates.