ABSTRACT
Despite ample evidence of the efficacy and effectiveness of evidence-based parenting programs (EBPPs) within research-led environments, there is very little evidence of maintenance of effectiveness when programs are delivered as part of regular service provision. The present study examined the effectiveness of EBPPs provided during a period of sustained service-led implementation in comparison to research-led effectiveness evaluation. Data from 3706 parents who received EBPPs during sustained implementation by services were compared to data from 1390 parents who had participated in an earlier researcher-led effectiveness trial of a national roll-out of EBPPs in England. In both phases, parents completed measures of child behavior problems, parenting style and parental mental well-being prior to starting parenting programs (pre-test), at the end of the programs (post) and at 12-months follow up. Results from Generalized Estimating Equations controlling for potential covariates indicated significant improvements in child behavior problems during sustained implementation, similar to the effectiveness phase; significant improvements in parenting style which were larger than the effectiveness phase at 12-month follow up; and significant improvements in parental mental well- being. Our findings demonstrate effective maintenance of gains when EBPPs are provided as part of regular provision across a large sample of English parents. Successful long-term implementation should consider effectiveness of EBPPs across the population, given the large contextual changes that take place between researcher-led evaluations and service take-up. Our findings support the integration of EBPPs in public health approaches to addressing child behavior problems and parent well-being.
ABSTRACT
Tau is a microtubule (MT)-stabilizing protein that is altered in Alzheimer's disease (AD) and other tauopathies. It is hypothesized that the hyperphosphorylated, conformationally altered, and multimeric forms of tau lead to a disruption of MT stability; however, direct evidence is lacking in vivo. In this study, an in vivo stable isotope-mass spectrometric technique was used to measure the turnover, or dynamicity, of MTs in brains of living animals. We demonstrated an age-dependent increase in MT dynamics in two different tau transgenic mouse models, 3xTg and rTg4510. MT hyperdynamicity was dependent on tau expression, since a reduction of transgene expression with doxycycline reversed the MT changes. Treatment of rTg4510 mice with the epothilone, BMS-241027, also restored MT dynamics to baseline levels. In addition, MT stabilization with BMS-241027 had beneficial effects on Morris water maze deficits, tau pathology, and neurodegeneration. Interestingly, pathological and functional benefits of BMS-241027 were observed at doses that only partially reversed MT hyperdynamicity. Together, these data suggest that tau-mediated loss of MT stability may contribute to disease progression and that very low doses of BMS-241027 may be useful in the treatment of AD and other tauopathies.
Subject(s)
Cognition Disorders/drug therapy , Epothilones/therapeutic use , Microtubules/pathology , Nerve Degeneration/drug therapy , Tauopathies/drug therapy , Tubulin Modulators/therapeutic use , tau Proteins/physiology , Animals , Brain/drug effects , Brain/metabolism , Brain/pathology , Cognition Disorders/complications , Cognition Disorders/metabolism , Disease Models, Animal , Dose-Response Relationship, Drug , Doxycycline/pharmacology , Drug Evaluation, Preclinical/methods , Drug Evaluation, Preclinical/psychology , Epothilones/pharmacology , Female , Hippocampus/drug effects , Hippocampus/pathology , Male , Maze Learning/drug effects , Mice , Mice, Inbred C57BL , Mice, Transgenic , Microtubules/drug effects , Tauopathies/complications , Tauopathies/genetics , Tauopathies/pathology , Tauopathies/psychology , Tubulin Modulators/pharmacology , tau Proteins/antagonists & inhibitors , tau Proteins/biosynthesis , tau Proteins/geneticsABSTRACT
Uncertainty exists with respect to the extent to which chewing gum may attenuate stress-induced rises in cortisol secretion (Johnson, Jenks, Miles, Albert, & Cox, 2011; Scholey et al., 2009; Smith, 2010). The present study used the Trier Social Stress Task (TSST: Kirschbaum, Pirke, & Hellhammer, 1993), a task known to elevate cortisol secretion (Kudielka, Schommer, Hellhammer, & Kirschbaum, 2004), in order to examine the moderating physiological and subjective effects of chewing gum on social stress. Forty participants completed the TSST either with or without chewing gum. As expected, completion of the TSST elevated both cortisol and subjective stress levels, whilst impairing mood. Although gum moderated the perception of stress, cortisol concentrations were higher following the chewing of gum. The findings are consistent with Smith (2010) who argued that elevations in cortisol following the chewing of gum reflect heightened arousal. The findings suggest that chewing gum only benefits subjective measures of stress. The mechanism remains unclear; however, this may reflect increased cerebral blood flow, cognitive distraction, and/or effects secondary to task facilitation.
