Early postoperative serum S100β levels predict ongoing brain damage after meningioma surgery: a prospective observational study

INTRODUCTION: Elevated serum levels of S100β, an astrocyte-derived protein, correlate with unfavourable neurological outcomes following cardiac surgery, neurotrauma, and resuscitation. This study evaluated whether pre-/postoperative serum S100β levels correlate with unfavourable clinical and radiological findings in patients undergoing elective meningioma resection. METHODS: In 52 consecutive patients admitted for meningioma surgery, serum S100β levels were determined upon admission and immediately, 24 hours, and 48 hours after surgery. All patients underwent complete pre- and postoperative neurological examination and mini-mental state examination. Radiological evaluation included preoperative magnetic resonance imaging (MRI) and postoperative computed tomography. Tumour volume, brain edema, and bleeding volume were calculated using BrainSCAN™ software. RESULTS: Preoperative S100β levels did not correlate with the tumour characteristics demonstrated by preoperative MRI (for example, tumour volume, edema volume, ventricular asymmetry, and/or midline shift). Preoperative serum S100β levels (0.065 ± 0.040 μg/l) were significantly lower than the levels measured immediately (0.138 ± 0.081 μg/l), 24 hours (0.142 ± 0.084 μg/l), and 48 hours (0.155 ± 0.119 μg/l) postoperatively (p < 0.0001). Significantly greater postcraniotomy S100β levels were observed with prolonged surgery (p = 0.039), deterioration in the mini-mental state examination (p = 0.005, 0.011, and 0.036 for pre versus immediate, 24 hours, and 48 hours postsurgery, respectively), and with postoperative brain computed tomography evidence of brain injury; bleeding was associated with higher serum S100β levels at 24 and 48 hours after surgery (p = 0.046, 95% confidence interval [CI] -0.095 to -0.001 and p = 0.034, 95% CI -0.142 to -0.006, respectively) as was the presence of midline shift (p = 0.005, 95% CI -0.136 to -0.025 and p = 0.006, 95% CI -0.186 to -0.032, respectively). Edema was associated with higher serum S100β levels immediately (p = 0.022, 95% CI -0.092 to -0.007) and at 48 hours after surgery (p = 0.017, 95% CI -0.142 to -0.026). The degree of elevation in S100β levels at 24 and 48 hours after surgery also correlated with the severity of midline shift and edema. CONCLUSION: In patients with meningioma, serum S100β levels perform poorly as an indicator of tumour characteristics but may suggest ongoing postcraniotomy injury. Serum S100β levels may serve as a potentially useful early marker of postcraniotomy brain damage in patients undergoing elective meningioma resection

Involvement of Interferon-System in the Regulation of Cell Growth and Differentiation

In this report we review the current knowledge on the involvement of the interferon (IFN) system in the regulation of cell growth and differentiation. We also summarize our own data which provide evidence for the strong correlation between IFN-mediated growth-arrest of transformed cells and the elevated enzymatic activity of an IFN-induced protein. Similarly, it is demonstrated that elevated levels of IFN-induced proteins accompany the early phases of in-vitro cell differentiation. IFN-treatment of NIH/3T3 mouse fibroblasts transformed by Moloney-murine sarcoma virus ( MSV) resulted in a significant reduction in the rates of cell growth, protein synthesis and cloning efficiency. In parallel, 2-5A-synthetase activity was induced ten-fold above the background level. Treatment of these cells for 3 days with 450 international units (lU)/ml of IFN followed by its removal, resulted in a gradual increase in all parameters associated with cell growth while the 2-5A-synthetase activity was reduced to its normal level. However, almost no recovery occurred when cells were treated with 1,800 IU/ml. In parallel, 2-5A-synthetase activity remained highly elevated even at 3 days after the removal of IFN. In these cells, the expression of both c-myc and v-mos was reduced rapidly following IFN treatment. Upon removal of IFN after 24 h of treatment, the expression of both genes was resumed but with a different kinetics, suggesting that different mechanisms are responsible for the reduction in gene expression. In rat skeletal muscle cultures which differentiate to form myotubes, the level of both 2-5A-synthetase and protein kinase activities was transiently elevated, reaching a peak at 3 days followed by a decrease to background levels. This peak activity precedes the appearance of the major muscle differentiating proteins

Neural traces of stress: cortisol related sustained enhancement of amygdala-hippocampal functional connectivity

Stressful experiences modulate neuro-circuitry function, and the temporal trajectory of these alterations, elapsing from early disturbances to late recovery, heavily influences resilience and vulnerability to stress. Such effects of stress may depend on processes that are engaged during resting-state, through active recollection of past experiences and anticipation of future events, all known to involve the default mode network (DMN). By inducing social stress and acquiring resting-state functional magnetic resonance imaging (fMRI) before stress, immediately following it, and 2 h later, we expanded the time-window for examining the trajectory of the stress response. Throughout the study repeated cortisol samplings and self-reports of stress levels were obtained from 51 healthy young males. Post-stress alterations were investigated by whole brain resting-state functional connectivity (rsFC) of two central hubs of the DMN: the posterior cingulate cortex (PCC) and hippocampus. Results indicate a ’recovery’ pattern of DMN connectivity, in which all alterations, ascribed to the intervening stress, returned to pre-stress levels. The only exception to this pattern was a stress-induced rise in amygdala-hippocampal connectivity, which was sustained for as long as 2 h following stress induction. Furthermore, this sustained enhancement of limbic connectivity was inversely correlated to individual stress-induced cortisol responsiveness (AUCi) and characterized only the group lacking such increased cortisol (i.e., non-responders). Our observations provide evidence of a prolonged post-stress response profile, characterized by both the comprehensive balance of most DMN functional connections and the distinct time and cortisol dependent ascent of intra-limbic connectivity. These novel insights into neuro-endocrine relations are another milestone in the ongoing search for individual markers in stress-related psychopathologies

Anxiety and cognitive bias in children and young people who stutter

Psychologists recognise various forms of anxiety, such as generalized anxiety disorder, separation anxiety and social phobia. People who stutter are at risk of elevated levels of anxiety, especially social phobia. Recent research has suggested that anxiety may be caused and maintained by cognitive biases such as preferentially allocating attention towards threat stimuli. These biases can be re-trained using cognitive bias modification with resulting improvements in levels of anxiety. In the present study, we measured different forms of anxiety and attentional bias for faces among 8-18 year olds attending the Michael Palin Centre for treatment for stuttering. The clients and their parent(s) completed the child and parent versions, respectively, of the Screen for Childhood Anxiety Related Emotional Disorders (SCARED), which provides an overall anxiety score and sub-scores, with clinical cut-offs, for generalized anxiety disorder, separation anxiety, social phobia, school avoidance and panic. The clients also performed a computerised measure of attentional bias for faces, using schematic stimuli. Levels of anxiety were higher than in the general population, and prevalence increased with age. There was a significant correlation between SCARED scores produced by clients and their parents. Socially anxious participants showed a bias towards sad faces

ZYG11A Is Expressed in Epithelial Ovarian Cancer and Correlates With Low Grade Disease

The insulin-like growth factors (IGF) are important players in the development of gynecological malignancies, including epithelial ovarian cancer (EOC). The identification of biomarkers that can help in the diagnosis and scoring of EOC patients is of fundamental importance in clinical oncology. We have recently identified the ZYG11A gene as a new candidate target of IGF1 action. The aim of the present study was to evaluate the expression of ZYG11A in EOC patients and to correlate its pattern of expression with histological grade and pathological stage. Furthermore, and in view of previous analyses showing an interplay between ZYG11A, p53 and the IGF1 receptor (IGF1R), we assessed a potential coordinated expression of these proteins in EOC. In addition, zyg11a expression was assessed in ovaries and uteri of growth hormone receptor (GHR) knock-out mice. Tissue microarray analysis was conducted on 36 patients with EOC and expression of ZYG11A, IGF1R and p53 was assessed by immunohistochemistry. Expression levels were correlated with clinical parameters. qPCR was employed to assess zyg11a mRNA levels in mice tissues. Our analyses provide evidence of reduced ZYG11A expression in high grade tumors, consistent with a putative tumor suppressor role. In addition, an inverse correlation between ZYG11A and p53 levels in individual tumors was noticed. Taken together, our data justify further exploration of the role of ZYG11A as a novel biomarker in EOC

NPT088 reduces both amyloid-b and tau pathologies in transgenic mice

Introduction: Alzheimer’s disease (AD) is characterized by appearance of both extracellular senile plaques and intracellular neurofibrillary tangles, comprised of aggregates of misfolded amyloid-b (Ab) and hyper-phosphorylated tau, respectively. In a previous study, we demonstrated that g3p, a capsid protein from bacteriophage M13, binds to and remodels misfolded aggregates of proteins that assume an amyloid conformation. We engineered a fusion protein (“NPT088”) consisting of the active fragment of g3p and human-IgG1-Fc. Methods: Aged Tg2576 mice or rTg4510 mice received NPT088 weekly via IP injection. Cognitive and/or functional motor endpoints were monitored during dosing. Pathology was quantified biochemically and immunohistochemically. Results: NPT088-lowered Ab plaque and improved cognitive performance of aged Tg2576 mice. Moreover, NPT088 reduced phospho-tau pathology, reduced brain atrophy, and improved cognition in rTg4510 mice. Discussion: These observations establish NPT088 as a novel therapeutic approach and potential drug class that targets both Ab and tau, the hallmark pathologies of AD

Investigation of attentional bias in obsessive compulsive disorder with and without depression in visual search

Copyright: © 2013 Morein-Zamir et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are creditedWhether Obsessive Compulsive Disorder (OCD) is associated with an increased attentional bias to emotive stimuli remains controversial. Additionally, it is unclear whether comorbid depression modulates abnormal emotional processing in OCD. This study examined attentional bias to OC-relevant scenes using a visual search task. Controls, non-depressed and depressed OCD patients searched for their personally selected positive images amongst their negative distractors, and vice versa. Whilst the OCD groups were slower than healthy individuals in rating the images, there were no group differences in the magnitude of negative bias to concern-related scenes. A second experiment employing a common set of images replicated the results on an additional sample of OCD patients. Although there was a larger bias to negative OC-related images without pre-exposure overall, no group differences in attentional bias were observed. However, OCD patients subsequently rated the images more slowly and more negatively, again suggesting post-attentional processing abnormalities. The results argue against a robust attentional bias in OCD patients, regardless of their depression status and speak to generalized difficulties disengaging from negative valence stimuli. Rather, post-attentional processing abnormalities may account for differences in emotional processing in OCD.Peer reviewedFinal Published versio