Distinguishing tumor admixed in a radiation necrosis (RN) background: 1H and 2H MR with a novel mouse brain-tumor/RN model

PURPOSE: Distinguishing radiation necrosis (RN) from recurrent tumor remains a vexing clinical problem with important health-care consequences for neuro-oncology patients. Here, mouse models of pure tumor, pure RN, and admixed RN/tumor are employed to evaluate hydrogen ( MATERIALS AND METHODS: A pipeline of common quantitative RESULTS: Differences in quantitative CONCLUSIONS: These findings, employing a pipeline of quantitativ

Reliability and Diagnostic Performance of CT Imaging Criteria in the Diagnosis of Tuberculous Meningitis

The original publication is available at http:// www.plosone.orgPublication of this article was funded by the Stellenbosch University Open Access Fund.Introduction: Abnormalities on CT imaging may contribute to the diagnosis of tuberculous meningitis (TBM). Recently, an expert consensus case definition (CCD) and set of imaging criteria for diagnosing basal meningeal enhancement (BME) have been proposed. This study aimed to evaluate the sensitivity, specificity and reliability of these in a prospective cohort of adult meningitis patients. Methods: Initial diagnoses were based on the CCD, classifying patients into: ‘Definite TBM’ (microbiological confirmation), ‘Probable TBM’ (diagnostic score $10), ‘Possible TBM’ (diagnostic score 6–9), ‘Not TBM’ (confirmation of an alternative diagnosis) or ‘Uncertain’ (diagnostic score of ,6). CT images were evaluated independently on two occasions by four experienced reviewers. Intra-rater and inter-rater agreement were calculated using the kappa statistic. Sensitivities and specificities were calculated using both ‘Definite TBM’ and either ‘Definite TBM’ or ‘Probable TBM’ as gold standards. Results: CT scan criteria for BME had good intra-rater agreement (k range 0.35–0.78) and fair to moderate inter-rater agreement (k range 0.20–0.52). Intra- and inter-rater agreement on the CCD components were good to fair (k = ranges 0.47–0.81 and 0.21–0.63). Using ‘Definite TBM’ as a gold standard, the criteria for BME were very specific (61.5%–100%), but insensitive (5.9%–29.4%). Similarly, the imaging components of the CCD were highly specific (69.2–100%) but lacked sensitivity (0–56.7%). Similar values were found when using ‘Definite TBM’ or ‘Probable TBM’ as a gold standard. Discussion: The fair to moderate inter-rater agreement and poor sensitivities of the criteria for BME suggest that little reliance should be placed in these features in isolation. While the presence of the CCD criteria of acute infarction or tuberculoma(s) appears useful as rule-in criteria, their absence is of little help in excluding TBM. The CCD and criteria for BME, as well as any new criteria, need to be standardized and validated in prospective cohort studies.Funding: KB received funding from the Discovery Foundation (Academic Fellowship Award; http://www.discovery.co.za/portal/loggedout-individual/discoverycommunity- about), College of Neurology of South Africa (K.M. Browse Award; http://www.collegemedsa.ac.za/Default.aspx ) and the University of Stellenbosch. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Publisher's versio

Predicting Individuals' Learning Success from Patterns of Pre-Learning MRI Activity

Performance in most complex cognitive and psychomotor tasks improves with training, yet the extent of improvement varies among individuals. Is it possible to forecast the benefit that a person might reap from training? Several behavioral measures have been used to predict individual differences in task improvement, but their predictive power is limited. Here we show that individual differences in patterns of time-averaged T2*-weighted MRI images in the dorsal striatum recorded at the initial stage of training predict subsequent learning success in a complex video game with high accuracy. These predictions explained more than half of the variance in learning success among individuals, suggesting that individual differences in neuroanatomy or persistent physiology predict whether and to what extent people will benefit from training in a complex task. Surprisingly, predictions from white matter were highly accurate, while voxels in the gray matter of the dorsal striatum did not contain any information about future training success. Prediction accuracy was higher in the anterior than the posterior half of the dorsal striatum. The link between trainability and the time-averaged T2*-weighted signal in the dorsal striatum reaffirms the role of this part of the basal ganglia in learning and executive functions, such as task-switching and task coordination processes. The ability to predict who will benefit from training by using neuroimaging data collected in the early training phase may have far-reaching implications for the assessment of candidates for specific training programs as well as the study of populations that show deficiencies in learning new skills

Effectiveness and cost-effectiveness of a group-based pain self-management intervention for patients undergoing total hip replacement: Feasibility study for a randomized controlled trial

Background: Total hip replacement (THR) is a common elective surgical procedure and can be effective for reducing chronic pain. However, waiting times can be considerable. A pain self-management intervention may provide patients with skills to more effectively manage their pain and its impact during their wait for surgery. This study aimed to evaluate the feasibility of conducting a randomized controlled trial to assess the effectiveness and cost-effectiveness of a group-based pain self-management course for patients undergoing THR.Methods: Patients listed for a THR at one orthopedic center were posted a study invitation pack. Participants were randomized to attend a pain self-management course plus standard care or standard care only. The lay-led course was delivered by Arthritis Care and consisted of two half-day sessions prior to surgery and one full-day session after surgery. Participants provided outcome and resource-use data using a diary and postal questionnaires prior to surgery and one month, three months and six months after surgery. Brief telephone interviews were conducted with non-participants to explore barriers to participation.Results: Invitations were sent to 385 eligible patients and 88 patients (23%) consented to participate. Interviews with 57 non-participants revealed the most common reasons for non-participation were views about the course and transport difficulties. Of the 43 patients randomized to the intervention group, 28 attended the pre-operative pain self-management sessions and 11 attended the post-operative sessions. Participant satisfaction with the course was high, and feedback highlighted that patients enjoyed the group format. Retention of participants was acceptable (83% of recruited patients completed follow-up) and questionnaire return rates were high (72% to 93%), with the exception of the pre-operative resource-use diary (35% return rate). Resource-use completion rates allowed for an economic evaluation from the health and social care payer perspective.Conclusions: This study highlights the importance of feasibility work prior to a randomized controlled trial to assess recruitment methods and rates, barriers to participation, logistics of scheduling group-based interventions, acceptability of the intervention and piloting resource use questionnaires to improve data available for economic evaluations. This information is of value to researchers and funders in the design and commissioning of future research.Trial registration: Current Controlled Trials ISRCTN52305381. © 2014 Wylde et al.; licensee BioMed Central Ltd

Catechol-O-Methyltransferase (COMT) gene polymorphism and breast cancer risk in young women

Oestrogen exposure has long been considered to be a main risk factor of breast cancer. More recently, interest has also focused on the possible carcinogenic influence from oestrogen metabolites, such as catechol oestrogens. O-methylation, catalysed by Catechol-O-Methyltransferase (COMT), is one pathway by which the potentially carcinogenic catechol oestrogens can be inactivated. The gene coding for COMT protein contains a single-nucleotide polymorphism (SNP), resulting in an amino acid shift Val→Met, which has been shown to determine high- and low-activity configuration of the enzyme. We hypothesized that the low-activity allele, COMTMet, may be implicated in early onset breast cancer. In the present case–control study, including 126 young breast cancer patients (≤ 36 years) and 117 healthy female blood donors, we analysed the association between COMTMet genotype and risk of breast cancer. No significant difference in the frequency of low-/high-activity alleles was found between cases and controls, indicating that the polymorphism, as a single factor, may not contribute to breast carcinogenesis in young women. © 2001 Cancer Research Campaignhttp://www.bjcancer.co

Nuclear Factor Kappa B Activation Occurs in the Amnion Prior to Labour Onset and Modulates the Expression of Numerous Labour Associated Genes

Background: Prior to the onset of human labour there is an increase in the synthesis of prostaglandins, cytokines and chemokines in the fetal membranes, particular the amnion. This is associated with activation of the transcription factor nuclear factor kappa B (NFkB). In this study we characterised the level of NFkB activity in amnion epithelial cells as a measure of amnion activation in samples collected from women undergoing caesarean section at 39 weeks gestation prior to the onset of labour. Methodology/Principal Findings: We found that a proportion of women exhibit low or moderate NFkB activity while other women exhibit high levels of NFkB activity (n = 12). This activation process does not appear to involve classical pathways of NFkB activation but rather is correlated with an increase in nuclear p65-Rel-B dimers. To identify the full range of genes upregulated in association with amnion activation, microarray analysis was performed on carefully characterised nonactivated amnion (n = 3) samples and compared to activated samples (n = 3). A total of 919 genes were upregulated in response to amnion activation including numerous inflammatory genes such cyclooxygenase-2 (COX-2, 44-fold), interleukin 8 (IL-8, 6-fold), IL-1 receptor accessory protein (IL-1RAP, 4.5-fold), thrombospondin 1 (TSP-1, 3-fold) and, unexpectedly, oxytocin receptor (OTR, 24-fold). Ingenuity Pathway Analysis of the microarray data reveal the two main gene networks activated concurrently with amnion activation are i) cell death, cancer and morphology and ii) cell cycle, embryoni

Inhibitory effects of pharmacological doses of melatonin on aromatase activity and expression in rat glioma cells

Melatonin exerts oncostatic effects on different kinds of neoplasias, especially on oestrogen-dependent tumours. Recently, it has been described that melatonin, on the basis of its antioxidant properties, inhibits the growth of glioma cells. Glioma cells express oestrogen receptors and have the ability to synthesise oestrogens from androgens. In the present study, we demonstrate that pharmacological concentrations of melatonin decreases the growth of C6 glioma cells and reduces the local biosynthesis of oestrogens, through the inhibition of aromatase, the enzyme that catalyses the conversion of androgens into oestrogens. These results are supported by three types of evidence. Firstly, melatonin counteracts the growth stimulatory effects of testosterone on glioma cells, which is dependent on the local synthesis of oestrogens from testosterone. Secondly, we found that melatonin reduces the aromatase activity of C6 cells, measured by the tritiated water release assay. Finally, by (RT)–PCR, we found that melatonin downregulates aromatase mRNA steady-state levels in these glioma cells. We conclude that melatonin inhibits the local production of oestrogens decreasing aromatase activity and expression. By analogy to the implications of aromatase in other forms of oestrogen-sensitive tumours, it is conceivable that the modulation of the aromatase by pharmacological melatonin may play a role in the growth of glioblastomas

Exploring the relationship between video game expertise and fluid intelligence

Hundreds of millions of people play intellectually-demanding video games every day. What does individual performance on these games tell us about cognition? Here, we describe two studies that examine the potential link between intelligence and performance in one of the most popular video games genres in the world (Multiplayer Online Battle Arenas: MOBAs). In the first study, we show that performance in the popular MOBA League of Legends' correlates with fluid intelligence as measured under controlled laboratory conditions. In the second study, we also show that the age profile of performance in the two most widely-played MOBAs (League of Legends and DOTA II) matches that of raw fluid intelligence. We discuss and extend previous videogame literature on intelligence and videogames and suggest that commercial video games can be useful as 'proxy' tests of cognitive performance at a global population level