Human SLFN5 is a transcriptional co-repressor of STAT1-mediated interferon responses and promotes the malignant phenotype in glioblastoma.

We provide evidence that the IFN-regulated member of the Schlafen (SLFN) family of proteins, SLFN5, promotes the malignant phenotype in glioblastoma multiforme (GBM). Our studies indicate that SLFN5 expression promotes motility and invasiveness of GBM cells, and that high levels of SLFN5 expression correlate with high-grade gliomas and shorter overall survival in patients suffering from GBM. In efforts to uncover the mechanism by which SLFN5 promotes GBM tumorigenesis, we found that this protein is a transcriptional co-repressor of STAT1. Type-I IFN treatment triggers the interaction of STAT1 with SLFN5, and the resulting complex negatively controls STAT1-mediated gene transcription via interferon stimulated response elements. Thus, SLFN5 is both an IFN-stimulated response gene and a repressor of IFN-gene transcription, suggesting the existence of a negative-feedback regulatory loop that may account for suppression of antitumor immune responses in glioblastoma.

The effect of body position on developing ultrasound criteria for the assessment of the internal jugular vein.

Recent studies investigating chronic cerebrospinal venous insufficiency highlighted that intracranial venous return has not yet been routinely investigated by ultrasound in the normal population. This creates an absence of a reference standard and raises concerns that the approach introduces variations into the results. The primary objective of this study was to develop reference standards for the assessment of the internal jugular vein in a normal population. A prospective small-scale study was conducted. Internal jugular veins of 31 normal candidates were examined using B-Mode and PW Doppler. Measurements at proximal and mid-point internal jugular vein were taken in sitting (90°) and supine (0°) positions. Area measurements were taken during passive respiration in cm(2). Time average velocity measurements were taken during passive respiration over a 3-second period. Reflux measurements were taken after apnoea and reflux was recorded from any reversed flow. Measurements were taken three times; an average was calculated and statically analysed. Of the 31 participants, one was excluded from the study and 30 were suitable. The Mann-Whitney U test was used to analyse the results; all results (area, time average velocity and reflux) showed that there was a significant difference between the two positions with p < 0.05 (two-tailed). This pilot study does suggest that there is a significant difference in area, time average velocity and reflux measurements of the internal jugular vein when taken in the sitting and supine position, which could affect the outcome of chronic cerebrospinal venous insufficiency. A further large-scale study is required to validate and standardise the assessment of the internal jugular vein.

Determinants of carotid plaque instability: echoicity versus heterogeneity.

OBJECTIVE: to identify the echoicity and heterogeneity of carotid plaques associated with ipsilateral symptomatic and asymptomatic neurovascular presentations. DESIGN: cross-sectional study. MATERIALS: a total of 113 patients, with 127 symptomatic and asymptomatic plaques, were studied. METHODS: the duplex images of the plaques were analysed echoically in a computer by means of Grey Scale Median (GSM) [hypoechoic (low GSM), hyperechoic (high GSM)]. The presence or absence of at least two plaque regions within the plaque area being echoically uniform (no variation of echoicity), occupying each at least 10% of the plaque area and having GSM difference greater than the plaque GSM was evaluated to distinguish the heterogeneous (presence of this pattern) from the homogeneous (absence of this pattern) plaques. RESULTS: the symptomatic status was associated with plaques of low median GSM (10.5) and 88% prevalence of the homogeneous pattern as contrasted with the asymptomatic status that was associated with high median GSM (28) and 65% prevalence of the homogeneous pattern [(p=0.001 (GSM), p=0.003 (heterogeneity)]. CONCLUSIONS: symptomatic plaques were associated with hypoechoic and predominant homogeneous echo-pattern whereas the asymptomatic ones were associated with hyperechoic and less predominant homogeneous pattern.