Expression of the progenitor marker NG2/CSPG4 predicts poor survival and resistance to ionising radiation in glioblastoma

Glioblastoma (GBM) is a highly aggressive brain tumour, where patients respond poorly to radiotherapy and exhibit dismal survival outcomes. The mechanisms of radioresistance are not completely understood. However, cancer cells with an immature stem-like phenotype are hypothesised to play a role in radioresistance. Since the progenitor marker neuron-glial-2 (NG2) has been shown to regulate several aspects of GBM progression in experimental systems, we hypothesised that its expression would influence the survival of GBM patients. Quantification of NG2 expression in 74 GBM biopsies from newly diagnosed and untreated patients revealed that 50% express high NG2 levels on tumour cells and associated vessels, being associated with significantly shorter survival. This effect was independent of age at diagnosis, treatment received and hypermethylation of the O6-methylguanine methyltransferase (MGMT) DNA repair gene promoter. NG2 was frequently co-expressed with nestin and vimentin but rarely with CD133 and the NG2 positive tumour cells harboured genetic aberrations typical for GBM. 2D proteomics of 11 randomly selected biopsies revealed upregulation of an antioxidant, peroxiredoxin-1 (PRDX-1), in the shortest surviving patients. Expression of PRDX-1 was associated with significantly reduced products of oxidative stress. Furthermore, NG2 expressing GBM cells showed resistance to ionising radiation (IR), rapidly recognised DNA damage and effectuated cell cycle checkpoint signalling. PRDX-1 knockdown transiently slowed tumour growth rates and sensitised them to IR in vivo. Our data establish NG2 as an important prognostic factor for GBM patient survival, by mediating resistance to radiotherapy through induction of ROS scavenging enzymes and preferential DNA damage signalling

Association between visceral, cardiac and sensorimotor polyneuropathies in diabetes mellitus

Aims: Gastrointestinal complaints are common in diabetes mellitus. However, its association to peripheral sensorimotor and autonomic neuropathies is not well investigated. The aim was to assess skin, muscle, bone and visceral sensitivity in diabetes patients with sensorimotor neuropathy, and correlate these with gastrointestinal symptoms and degree of cardiac autonomic neuropathy. Methods: Twenty patients with sensorimotor neuropathy (65% type 2 diabetes, aged 58.3 ± 12.0 years, diabetes duration 15.8 ± 10.0 years) and 16 healthy controls were recruited. Cutaneous sensitivity to von Frey filaments, mechanical allodynia, muscle/bone/rectosigmoid sensitivities, and heart rate variability were examined. Gastrointestinal symptom scores (PAGI-SYM) and health-related quality of life (SF-36) were also recorded. Results: Patients displayed hypesthesia to von Frey filaments (p = 0.028), but no difference to muscle and bone pain sensitivities. Also, patients were hyposensitive to multimodal rectal stimulations (all p < 0.05), although they suffered more gastrointestinal complaints. Heart rate variability was reduced in the patient cohort. Rectal mechanical and cutaneous sensitivities correlated (p < 0.001), and both were associated with heart rate variability as well as PAGI-SYM and SF-36 scores (p < 0.01). Conclusions: In diabetic sensorimotor neuropathy there is substantial evidence of concomitant cutaneous, cardiac and visceral autonomic neuropathies. The neuropathy may reduce quality of life and explain the higher prevalence of gastrointestinal complaints

No Increase in Response Rate by Adding a Web Response Option to a Postal Population Survey: A Randomized Trial

Background: There is substantial interest in use of the Internet for surveys, but there have been few health-oriented, large, randomized trials of general population surveys on the Internet. It is unclear whether providing the option to respond via Internet increases the response rate, and to what degree the results will differ. Objective: The aim of the study was to evaluate changes in response rate and outcomes in a postal respiratory health survey by adding an optional Web response alternative. Methods: This was a randomized trial of a random sample of 4213 permanent residents of Norway, aged 20-40 years. Participants were randomized into a traditional survey arm, where they were asked to return the survey by mail, and an arm where they were also offered the option to respond via a Web form. Results: A total of 1928/4213 subjects responded, a response rate of 45.8% across both arms. The total response rate was 44.8% (944/2105) in the postal plus optional Internet response arm and 46.7% (984/2108) in the usual postal survey arm, with no statistically significant difference between the randomized groups (P = .24). In the optional Internet arm, 8.3% (175/2105) of the sample responded using the Internet and 36.5% (769/2105) responded by post. Thus, Internet response was chosen by 18.5% (175/944) of those who replied in the optional Internet arm. In the multivariate analysis, Internet response was associated with being male, frequency and type of Internet access (home users more likely to respond by Internet than work users), and smoking habit, with current smokers being more likely to be Internet responders. 57% preferred postal response (1102/1928), 38% preferred Internet response (733/1928), and 3% preferred telephone interview (54/1928), with no difference between randomization arms (P = .56). But among those who indicated that they preferred the Internet response and who were randomized to the optional Internet arm, only 47% actually chose the Internet response. Asthma prevalence was higher among participants choosing the Internet response mode (16.7% vs 12.4%). Conclusions: We failed to increase survey response rates by adding an optional Internet response. Asthma diagnosis was higher in the Internet response group, suggesting nonresponse bias. Method comparison studies should be carried out before Internet studies are accepted in new populations or new subject matters

Standardized computer-based organized reporting of EEG : SCORE - Second version

Standardized terminology for computer-based assessment and reporting of EEG has been previously developed in Europe. The International Federation of Clinical Neurophysiology established a taskforce in 2013 to develop this further, and to reach international consensus. This work resulted in the second, revised version of SCORE (Standardized Computer-based Organized Reporting of EEG), which is presented in this paper. The revised terminology was implemented in a software package (SCORE EEG), which was tested in clinical practice on 12,160 EEG recordings. Standardized terms implemented in SCORE are used to report the features of clinical relevance, extracted while assessing the EEGs. Selection of the terms is context sensitive: initial choices determine the subsequently presented sets of additional choices. This process automatically generates a report and feeds these features into a database. In the end, the diagnostic significance is scored, using a standardized list of terms. SCORE has specific modules for scoring seizures (including seizure semiology and ictal EEG patterns), neonatal recordings (including features specific for this age group), and for Critical Care EEG Terminology. SCORE is a useful clinical tool, with potential impact on clinical care, quality assurance, data-sharing, research and education