Low grade glioma: An Update for Radiologists

With the recent publication of a new World Health Organization (WHO) brain tumour classification that reflects increased understanding of glioma tumour genetics there is a need for radiologists to understand the changes and their implications for patient management. There has also been an increasing trend for adopting earlier, more aggressive surgical approaches to low grade glioma treatment. We will summarise these changes, give some context to the increased role of tumour genetics and discuss the associated implications for radiologists of their adoption. We will discuss the earlier and more radical surgical resection of low grade gliomas and what it means for imaging patients

The involvement of central corticotropin-releasing hormone and its receptors in sleep-wake regulation of mice

The corticotropin-releasing hormone (CRH) is widely recognised as the major activator of the hypothalamic-pituitary-adrenocortical (HPA) axis, thereby mediating neuroendocrine, autonomic, and behavioural responses to stress. Dysregulation of the release of stress hormones, caused by excessive CRH secretion from the hypothalamus, is frequently observed in patients with affective disorders such as depression. One of the cardinal symptoms of major depression is a severe impairment of sleep (e.g. reduced sleep intensity, disinhibition of rapid eye movement sleep (REMS), and early morning awakenings). Consequently, besides a role of CRH in stress-induced arousal, its additional contribution to spontaneous sleep-wake regulation was suggested in literature. Due to the lack of highly specific CRH receptor antagonists and adequate CRH receptor knockout animal models, the mechanism and pathways by which CRH communicates its arousal function remained indistinct. Up to now it is unclear whether CRH interferes with sleep by a direct central action, or if the activation of the HPA axis and the subsequent release of peripheral stress hormones are mandatory. The present study with conditional CNS-specific CRH receptor type 1 (CRH-R1 CKO) and conventional CRH receptor type 2 knockout mice (CRH-R2 KO), allows assessment of CRH effects on wakefulness and sleep separately from a functional HPA axis together with various levels of CRH receptor system functionality. In addition, challenging sleep homeostasis in these mouse lines by sleep deprivation allows investigating the involvement of CRH and its receptor system in basic sleep-wake regulatory processes. Besides slight dissimilarities between the baseline sleep profiles in the various genotypes, CRH-R1 CKO displayed a markedly different response to intracerebroventricular (i.c.v.) CRH injections. The dose-dependent increases in wakefulness and decreases in non-REM sleep (NREMS), which could be observed in all other mouse lines, were almost totally absent in CRH-R1 CKO. The dose-dependent REMS suppression on the other hand persisted in all, even CRH-R1 CKO, animals. This suggests that the centrally expressed CRH receptor type 1 (CRH-R1) but not the CRH receptor type 2 (CRH-R2), mediates the crucial effects of CRH on wake induction and NREMS suppression. Since REMS inhibition by CRH still occurred in CRH-R1 CKO animals pretreated with a highly specific CRH-R2 antagonist, the clear role of central CRH and both receptors in REMS suppression remains elusive. Sleep deprivation induced significant increases in plasma corticosterone levels in all mouse lines, demonstrating HPA axis activation and suggesting that all mice perceived sleep loss as a stressor. After termination of sleep deprivation, all animals responded with a significant increase of slow wave activity (SWA), an indicator of sleep intensity, followed by a rebound of NREMS. With the exception of CRH-R1 CKO mice, all mice furthermore similarly displayed REMS rebound. Another difference in response to sleep deprivation constitutes the course of SWA in CRH-R1 CKO which was significantly increased over baseline levels for a longer period as compared to all other mouse lines. Accordingly CRH-R1 CKO animals presumably sleep more intensely or efficiently than mice of the other breeding lines. These results suggest that CRH mediates the effects, at least the stressful component, of sleep loss, and moreover that CRH-R1 is essentially involved in sleep homeostasis. This study is the first to show considerable evidence for a crucial involvement of central CRH and CRH-R1 in arousal and the suppression of NREMS. It could further be shown that activation of the HPA axis is not a prerequisite of these effects. Additionally, the action of central CRH, mediated by CRH-R1 seems to influence sleep quality. The role of CRH-R2 has to be regarded as of a minor nature. The impact of CRH on REMS regulation demands further investigation

Agrammatic but numerate

A central question in cognitive neuroscience concerns the extent to which language enables other higher cognitive functions. In the case of mathematics, the resources of the language faculty, both lexical and syntactic, have been claimed to be important for exact calculation, and some functional brain imaging studies have shown that calculation is associated with activation of a network of left-hemisphere language regions, such as the angular gyrus and the banks of the intraparietal sulcus. We investigate the integrity of mathematical calculations in three men with large left-hemisphere perisylvian lesions. Despite severe grammatical impairment and some difficulty in processing phonological and orthographic number words, all basic computational procedures were intact across patients. All three patients solved mathematical problems involving recursiveness and structure-dependent operations (for example, in generating solutions to bracket equations). To our knowledge, these results demonstrate for the first time the remarkable independence of mathematical calculations from language grammar in the mature cognitive system

Reduction of low- and high-grade cervical abnormalities associated with high uptake of the HPV bivalent vaccine in Scotland

In Scotland, a national HPV immunisation programme began in 2008 for 12-13 year olds, with a catch-up campaign from 2008-2011 for those under the age of 18. To monitor the impact of HPV immunisation on cervical disease at the population level, a programme of national surveillance was established.  We analysed colposcopy data from a cohort of women born between 1988-1992 who entered the Scottish Cervical Screening Programme (SCSP) and were aged 20-21 in 2008-2012.  By linking datasets from the SCSP and colposcopy services, we observed a significant reduction in diagnoses of cervical intraepithelial neoplasia 1 (CIN 1) (RR 0.71, 95% CI 0.58 to 0.87, p=0.0008), CIN 2 (RR 0.5, 95% CI 0.4, 0.63, p<0.0001) and CIN 3 (RR 0.45, 95% CI 0.35 to 0.58, p< 0.0001) for women who received 3 doses of vaccine compared with unvaccinated women.  To our knowledge, this is one of the first studies to show a reduction of low and high grade cervical intraepithelial neoplasia associated with high uptake of the HPV bivalent vaccine at the population level. These data are very encouraging for countries that have achieved high HPV vaccine uptake

The neural basis of video gaming

Video game playing is a frequent recreational activity. Previous studies have reported an involvement of dopamine-related ventral striatum. However, structural brain correlates of video game playing have not been investigated. On magnetic resonance imaging scans of 154 14-year-olds, we computed voxel-based morphometry to explore differences between frequent and infrequent video game players. Moreover, we assessed the Monetary Incentive Delay (MID) task during functional magnetic resonance imaging and the Cambridge Gambling Task (CGT). We found higher left striatal grey matter volume when comparing frequent against infrequent video game players that was negatively correlated with deliberation time in CGT. Within the same region, we found an activity difference in MID task: frequent compared with infrequent video game players showed enhanced activity during feedback of loss compared with no loss. This activity was likewise negatively correlated with deliberation time. The association of video game playing with higher left ventral striatum volume could reflect altered reward processing and represent adaptive neural plasticity. Translational Psychiatry (2011) 1, e53; doi: 10.1038/tp.2011.53; published online 15 November 2011</p

Anti-cancer effects and mechanism of actions of aspirin analogues in the treatment of glioma cancer

INTRODUCTION: In the past 25 years only modest advancements in glioma treatment have been made, with patient prognosis and median survival time following diagnosis only increasing from 3 to 7 months. A substantial body of clinical and preclinical evidence has suggested a role for aspirin in the treatment of cancer with multiple mechanisms of action proposed including COX 2 inhibition, down regulation of EGFR expression, and NF-κB signaling affecting Bcl-2 expression. However, with serious side effects such as stroke and gastrointestinal bleeding, aspirin analogues with improved potency and side effect profiles are being developed. METHOD: Effects on cell viability following 24 hr incubation of four aspirin derivatives (PN508, 517, 526 and 529) were compared to cisplatin, aspirin and di-aspirin in four glioma cell lines (U87 MG, SVG P12, GOS – 3, and 1321N1), using the PrestoBlue assay, establishing IC50 and examining the time course of drug effects. RESULTS: All compounds were found to decrease cell viability in a concentration and time dependant manner. Significantly, the analogue PN517 (IC50 2mM) showed approximately a twofold increase in potency when compared to aspirin (3.7mM) and cisplatin (4.3mM) in U87 cells, with similar increased potency in SVG P12 cells. Other analogues demonstrated similar potency to aspirin and cisplatin. CONCLUSION: These results support the further development and characterization of novel NSAID derivatives for the treatment of glioma

Observation of Scaling Violations in Scaled Momentum Distributions at HERA

Charged particle production has been measured in deep inelastic scattering (DIS) events over a large range of $x$ and $Q^2$ using the ZEUS detector. The evolution of the scaled momentum, $x_p$, with $Q^2,$ in the range 10 to 1280 $GeV^2$, has been investigated in the current fragmentation region of the Breit frame. The results show clear evidence, in a single experiment, for scaling violations in scaled momenta as a function of $Q^2$.Comment: 21 pages including 4 figures, to be published in Physics Letters B. Two references adde

Potential conservation of circadian clock proteins in the phylum Nematoda as revealed by bioinformatic searches

Although several circadian rhythms have been described in C. elegans, its molecular clock remains elusive. In this work we employed a novel bioinformatic approach, applying probabilistic methodologies, to search for circadian clock proteins of several of the best studied circadian model organisms of different taxa (Mus musculus, Drosophila melanogaster, Neurospora crassa, Arabidopsis thaliana and Synechoccocus elongatus) in the proteomes of C. elegans and other members of the phylum Nematoda. With this approach we found that the Nematoda contain proteins most related to the core and accessory proteins of the insect and mammalian clocks, which provide new insights into the nematode clock and the evolution of the circadian system.Fil: Romanowski, Andrés. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Cronobiología; ArgentinaFil: Garavaglia, Matías Javier. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Ing.genética y Biolog.molecular y Celular. Area Virus de Insectos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Goya, María Eugenia. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Cronobiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Ghiringhelli, Pablo Daniel. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Ing.genética y Biolog.molecular y Celular. Area Virus de Insectos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Golombek, Diego Andres. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Cronobiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin