Lack of Effect of Propranolol on the Reconsolidation of Conditioned Fear Memory due to a Failure to Engage Memory Destabilisation.

The prospect of exploiting memory reconsolidation to treat mental health disorders has received great research interest, particularly following demonstrations that the ß-adrenergic receptor antagonist propranolol, which is safe for use in humans, can disrupt the reconsolidation of pavlovian conditioned fear memories. However, recent studies have failed to replicate the effects of propranolol on fear memory reconsolidation, and have questioned whether treatments based upon reconsolidation blockade would be robust enough for clinical translation. It remains possible, though, that studies reporting no effect of propranolol on memory reconsolidation could be due to a failure to engage the memory destabilisation process, which is necessary for the memory to become susceptible to disruption with amnestic agents. Demonstrating that memory destabilisation has not been engaged is challenging when only using behavioural measures, but there are molecular correlates of memory destabilisation that can be used to determine whether memory lability has been induced. Here, we attempted to replicate the classic finding that systemic administration of propranolol disrupts the reconsolidation of a pavlovian auditory fear memory. Following a failure to replicate, we manipulated the parameters of the memory reactivation session to enhance prediction error in an attempt to overcome the boundary conditions of reconsolidation. On finding no disruption of memory despite these manipulations, we examined the expression of the post-synaptic density protein Shank in the basolateral amygdala. Degradation of Shank has been shown to correlate with the induction of memory lability, but we found no effect on Shank expression, consistent with the lack of observed behavioural effects.

A methodology to design a performance management system in preventive care.

BACKGROUND: Preventive care has gained increasing attention in health reforms around the world due to its ability to reduce the burden of disease and to save health costs. Nevertheless, there is a gap in terms of the development of reliable systems to measure and evaluate performance of preventive care in order to support decision-making and increase service outcomes. The aim of this study is to define a methodology for designing a performance management system (PMS) in order to effectively support the planning, control and evaluation of preventive care and to identify the factors that influence such a process. METHODS: The methodology is based on the participatory action research approach, which implies collaboration between researchers and practitioners. The study was articulated in four phases and carried out in an Italian regional healthcare system that was undergoing a major reorganization process. RESULTS: The findings provide insights into the peculiarities that affect preventive care and highlight two categories of critical factors: general issues regarding the process and specific issues regarding preventive care. The first category includes the importance of interactions between academics, physicians and policy-makers, the impact of workloads and red tape on employee involvement and the increased conservation mechanisms during periods of institutional change. The second category concerns the strong heterogeneity of preventive activities within health organizations, the huge amount of regulations and the incompleteness of information systems. CONCLUSION: The development of a PMS for preventive care can best be served by collaborative methods that involve academics, professionals and policy-makers, whose roles and responsibilities must be clearly defined, and by an improvement in transparency and communication within organizations in order to enhance the involvement of different professionals at appropriate times and in appropriate ways. Key recommendations that may improve the maintenance and use of information systems are proposed to policy-makers.

Reduced development of experimental periodontitis by treatment with M40403, a superoxide dismutase mimetic.

M40403, [manganese(II)dichloro[(4R,9R,14R,19R)-3,10,13,20,26 pentaazatetracyclo[20.3.1.0.(4,9)0(14,19)]hexacosa-1(26),-22(23),24-triene]], is a low-molecular-weight, synthetic, manganese-containing superoxide dismutase mimetic that removes superoxide anions without interfering with other reactive species known to be involved in inflammatory responses (e.g., nitric oxide, NO and peroxynitrite, ONOO-). As such, M40403 represents an important pharmacological tool to dissect the roles of superoxide anion in acute and chronic inflammation. For this purpose, the pharmacological profile of M40403 was evaluated in a rat model of periodontitis. Periodontitis was induced in rats by placing a 2/0 braided silk around the lower left first molar. On day 8 the gingivomucosal tissue encircling the first molar was removed for biochemical and histological analysis. Ligation significantly increased inducible nitric oxide synthase activity and expression, and gingival tissue revealed increased neutrophil infiltration, lipid peroxidation and positive staining for nitrotyrosine formation and poly (ADP-ribose) polymerase activation. Ligation significantly increased Evans blue extravasation in gingivomucosal tissue and alveolar bone destruction. Intraperitoneal injection of M40403 (10 mg/kg daily for 8 days) significantly decreased all of the above-described markers of inflammation. This suggests compounds that inhibit the generation of superoxide anion, such as M40403 may be potentially useful for the treatment of periodontitis.