Pre-surgical mapping of eloquent cortex for paediatric epilepsy surgery candidates: Evidence from a review of advanced functional neuroimaging

Purpose: A review of all published evidence for mapping eloquent (motor, language and memory) cortex using advanced functional neuroimaging (functional magnetic resonance imaging [fMRI] and magnetoencephalography [MEG]) for paediatric epilepsy surgery candidates has not been conducted previously. Research in this area has predominantly been in adult populations and applicability of these techniques to paediatric populations is less established. Methods: A review was performed using an advanced systematic search and retrieval of all published papers examining the use of functional neuroimaging for paediatric epilepsy surgery candidates. Results: Of the 2,724 papers retrieved, 34 met the inclusion criteria. Total paediatric participants identified were 353 with an age range of 5 months-19 years. Sample sizes and comparisons with alternative investigations to validate techniques are small and variable paradigms are used. Sensitivity 0.72 (95% CI 0.52-0.86) and specificity 0.60 (95% CI 0.35-0.92) values with a Positive Predictive Value of 74% (95% CI 61-87) and a Negative Predictive Value of 65% (95% CI 52-78) for fMRI language lateralisation with validation, were obtained. Retrieved studies indicate evidence that both fMRI and MEG are able to provide information lateralising and localising motor and language functions. Conclusions: A striking finding of the review is the paucity of studies (n = 34) focusing on the paediatric epilepsy surgery population. For children, it remains unclear which language and memory paradigms produce optimal activation and how these should be quantified in a statistically robust manner. Consensus needs to be achieved for statistical analyses and the uniformity and yield of language, motor and memory paradigms. Larger scale studies are required to produce patient series data which clinicians may refer to interpret results objectively. If functional imaging techniques are to be the viable alternative for pre-surgical mapping of eloquent cortex for children, paradigms and analyses demonstrating concordance with independent measures must be developed

A New Class of Safe Oligosaccharide Polymer Therapy To Modify the Mucus Barrier of Chronic Respiratory Disease

The host- and bacteria-derived extracellular polysaccharide coating of the lung is a considerable challenge in chronic respiratory disease and is a powerful barrier to effective drug delivery. A low molecular weight 12–15-mer alginate oligosaccharide (OligoG CF-5/20), derived from plant biopolymers, was shown to modulate the polyanionic components of this coating. Molecular modeling and Fourier transform infrared spectroscopy demonstrated binding between OligoG CF-5/20 and respiratory mucins. Ex vivo studies showed binding induced alterations in mucin surface charge and porosity of the three-dimensional mucin networks in cystic fibrosis (CF) sputum. Studies in Humans showed that OligoG CF-5/20 is safe for inhalation in CF patients with effective lung deposition and modifies the viscoelasticity of CF-sputum. OligoG CF-5/20 is the first inhaled polymer therapy, represents a novel mechanism of action and therapeutic approach for the treatment of chronic respiratory disease, and is currently in Phase IIb clinical trials for the treatment of CF

Increased plasma thioredoxin levels in patients with sepsis: positive association with macrophage migration inhibitory factor.

PURPOSE: To establish the relationship between plasma levels of thioredoxin (Trx) and macrophage migration inhibitory factor (MIF) in systemic inflammatory stress syndrome (SIRS)/sepsis. METHODS: Enzyme-linked immunosorbent assay measurements of Trx, MIF, IL-6, -8, and -10 and enzyme-linked fluorescent assay determination of procalcitonin (PCT) in plasma from patients with SIRS/sepsis, neutropenic sepsis, healthy volunteers and pre-oesophagectomy patients. RESULTS: Thioredoxin was significantly higher in SIRS/sepsis patients [101.3 ng ml(−1), interquartile range (IQR) 68.7–155.6, n = 32] compared with that in healthy controls (49.5 ng ml(−1), IQR 31.4–71.1, P < 0.001, n = 17) or pre-oesophagectomy patients (40.5 ng ml(−1), IQR 36.9–63.2, P < 0.01, n = 7), but was not raised in neutropenics (n = 5). MIF levels were also significantly higher in SIRS/sepsis patients (12.1 ng ml(−1), IQR 9.5–15.5, n = 35), but not in the neutropenic group, when compared with healthy controls (9.3 ng ml(−1), IQR 7.3–10.7, P < 0.01, n = 20). Trx levels correlated, positively, with MIF levels and APACHE II scores. Plasma levels of IL-6, -8 and -10 and PCT increased significantly in patients with SIRS/sepsis (P < 0.001) and with neutropenic sepsis, but did not correlate with Trx or MIF levels. CONCLUSION: Plasma levels of Trx, MIF, IL-6, -8, -10 and PCT were raised in patients with SIRS/sepsis. Comparisons between mediators suggest a unique correlation of Trx with MIF. Moreover, Trx and MIF differed from cytokines and PCT in that levels were significantly lower in patients with neutropenia compared with the main SIRS/sepsis group. By contrast, IL-8 and PCT levels were significantly greater in the neutropenic patient group. The link between MIF and Trx highlighted in this study has implications for future investigations into the pathogenesis of SIRS/sepsis