Disturbance of rapid eye movement (REM) sleep appears early in both patients with Huntington's disease (HD) and mouse models of HD. Selective serotonin reuptake inhibitors are widely prescribed for patients with HD, and are also known to suppress REM sleep in healthy subjects. To test whether selective serotonin reuptake inhibitors can correct abnormal REM sleep and sleep-dependent brain oscillations in HD mice, we treated wild-type and symptomatic R6/2 mice acutely with vehicle and paroxetine (5, 10, and 20 mg/kg). In addition, we treated a group of R6/2 mice chronically with vehicle or paroxetine (20 mg/kg/day) for 8 weeks, with treatment starting before the onset of overt motor symptoms. During and after treatment, we recorded electroencephalo-gram/electromyogram from the mice. We found that both acute and chronic paroxetine treatment normalized REM sleep in R6/2 mice. However, only chronic paroxetine treatment prevented the emergence of abnormal low-gamma (25-45 Hz) electroencephalogram oscillations in R6/2 mice, an effect that persisted for at least 2 weeks after treatment stopped. Chronic paroxetine treatment also normalized REM sleep theta rhythm in R6/2 mice, but, interestingly, this effect was restricted to the treatment period. By contrast, acute paroxetine treatment slowed REM sleep theta rhythm in WT mice but had no effect on abnormal theta or low-gamma oscillations in R6/2 mice. Our data show that paroxetine treatment, when initiated before the onset of symptoms, corrects both REM sleep disturbances and abnormal brain oscillations, suggesting a possible mechanistic link between early disruption of REM sleep and the subsequent abnormal brain activity in HD mice.

The ability of the vitamin E (RRR-A-tocopherol) derivatives A-tocopheryl succinate (A-TOS) and A-tocopheryloxyacetic acid (A-TEA) to suppress tumor growth in preclinical animal models has recently led to increased interest in their potential use for treating human cancer. To make the use of these vitamin E analogues more clinically relevant, we compared the antitumor efficacy of orally and i.p. delivered forms of A-TEA and A-TOS against a murine mammary cancer (4T1) that bears resemblance to human breast cancer because of its poor immunogenicity and high metastatic potential. In cell culture studies, we showed that both compounds inhibited tumor colony formation and induced apoptotic death of tumor cells. To avoid solubility concerns associated with the hydrophobicity of A-TEA and A-TOS, we used the vesiculated forms of A-TEA (VA-TEA) and A-TOS (VA-TOS) for the in vivo tumor studies. Both compounds inhibited the growth of preestablished 4T1 tumors when given i.p. However, when given by oral gavage, only the esterase-resistant VA-TEA was able to suppress primary tumor growth and reduce lung metastasis. To make this approach more translatable to the clinic, A-TEA was incorporated into the diet and fed to tumor-bearing mice. We report here for the first time that dietary A-TEA delivery significantly inhibited primary tumor growth and dramatically reduced spontaneous metastatic spread to the lung in prophylactic and therapeutic settings. This study suggests that dietary A-TEA could prove useful as a relatively easy and effective modality for treating metastatic breast cancer.

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Our results support the hypothesis that carriers of the PlA2 allele might have an increased risk for ACS. PlA2 homozygosity was associated with an inadequate response to aspirin therapy. Our data further suggest that patients with PlA2 allele homozygosity might benefit from antiplatelet therapy based on adenosine diphosphate antagonists throughout secondary treatment for prevention of ACS.

The most stigmatised area of Budapest, the Eighth District (Józsefváros) has been undergoing significant urban and social change since 1989. However, compared with what rent gap theory would have forecast, gentrification took off relatively late. After a historical narrative of how rent gap in Józsefváros had been produced throughout the 20 th century, we will argue that examining the mechanisms and outcomes of the three dominant dynamics of rescaling urban governance in Hungary-decentralisation without the redistribution of resources in the 1990s; EU accession and Europeanisation of public policies from the 2000s; and recentralisation after 2010-help us understand when, where and how gentrification has been unwinding in Middle-Józsefváros, the most dilapidated area of the Eighth District. The article will present three case studies of local urban regeneration as paradigmatic for the three rescaling dynamics: Corvin Promenade, Magdolna Quarter Programme, and the ongoing Orczy Quarter project. It will show the underlying revanchist policies and discourses in each case. The main aim of the current paper is to illustrate how a scale-sensitive political economic approach can go beyond the mainstream public and political discourse in scrutinising gentrification, through shedding light on structural factors contributing to exclusion, criminalisation, displacement, and othering.