Bar press durations as a reliable and robust measure of frustration-related operant behavior: Sensitivity to incentive downshift and dose-response paradigms.

In humans, frustrating experiences are known to trigger relapse events and individuals with higher frustration intolerance show increased risk of developing substance use disorders (SUDs). Despite this clear relationship, frustration-related behavior is seldom studied concurrently with self-administration behavior in rodent models. A major obstacle has been the lack of robust, quantitative assays of frustration-related operant behavior thus far. In previous work, we identified increased bar press (BP) durations in response to frustrating conditions in rats self-administering natural or drug rewards. Here, to propose BP durations as a measure of frustration-related behavior, we conducted an operant successive negative contrast (oSNC) study and found that increases in BP durations are observed in the absence of increased effort, providing evidence that this is a psychological phenomenon. Moreover, we assess the viability of widespread use of BP duration measurements as a behavioral tool by quantifying performance as it pertains to sensitivity, robustness, replicability, and sex differences. We conclude that increases in BP durations are a highly sensitive psychological response to frustrating conditions and that this measure is robust, replicable, and applicable to both sexes.

Trolox enhances curcumin's cytotoxicity through induction of oxidative stress.

Curcumin, a natural polyphenol in the spice turmeric, has been found to exhibit anticancer activity. Although curcumin is generally considered an antioxidant, it is also able to elicit apoptosis through the generation of ROS, thereby functioning as a pro-oxidant in cancer cells. The present study investigated the effects of antioxidant pretreatment on curcumin-induced cytotoxicity in the human cancer cell lines A2780, MCF-7, and MDA-MB-231. Cytotoxicity was enhanced by trolox, vitamin C or vitamin E; trolox, a water soluble vitamin E derivative, was the most potent. The combination of curcumin (10 µM) and trolox (10-50 µM) induced apoptosis of cancer cells as evidenced by PARP cleavage and caspase-3 activation. Furthermore, expression of the pro-apoptotic protein Bad was up-regulated and expression of the anti-apoptotic proteins Bcl-2 and Bcl-xl was down-regulated in cells that had been treated with trolox plus curcumin. ROS generation was detected in curcumin-treated cells and was significantly enhanced when cells were treated with trolox plus curcumin. Exogenous catalase or SOD1 did not alter cytotoxicity, while over-expression of either catalase or SOD1 did, pointing to the importance of intracellular hydrogen peroxide generation in cell killing. In conclusion, we demonstrated for the first time that antioxidants such as trolox can potentiate cancer cell killing by curcumin, a finding which may help in the development of novel drug combination therapies.

Adults with a diagnosis of cerebral palsy: a mapping review of long-term outcomes.

AIM: Cerebral palsy (CP) is recognized as a lifespan condition. This mapping review identifies outcomes that have been measured in adults with CP between 1970 and 2010 to determine if either the outcomes evaluated or the research methodologies have changed substantially. METHOD: We performed a literature review. For studies to be included, participants had to be 16 years or older and 80% of the sample had to have a diagnosis of CP. Articles were grouped by decade, and outcomes were categorized using the International Classification of Functioning, Disability and Health (ICF) framework and terminology. RESULTS: Fifty-eight articles were included in the mapping review. Both the number of studies and the types of outcomes investigated increased from 1970 to 2010. Outcomes representing the ICF component of Body Function and Structure were present across the period reviewed, whereas interest in contextual (personal or environmental) factors has primarily emerged since 2000. INTERPRETATION: Gaps were identified by the mapping review. Large age ranges and heterogeneity of sample populations made it difficult to determine if the outcomes reported were due to ageing or the long-term consequences of CP. In addition, most reviewed articles described outcomes categorically, with few papers providing explanations or solutions to reported outcomes.