Multimodal neuroimaging in presurgical evaluation of childhood epilepsy

In pre-surgical evaluation of pediatric epilepsy, the combined use of multiple imaging modalities for precise localization of the epileptogenic focus is a worthwhile endeavor. Advanced neuroimaging by high field Magnetic resonance imaging (MRI), diffusion tensor images, and MR spectroscopy have the potential to identify subtle lesions. 18F-FDG positron emission tomography and single photon emission tomography provide visualization of metabolic alterations of the brain in the ictal and interictal states. These techniques may have localizing value for patients which exhibit normal MRI scans. Functional MRI is helpful for non-invasively identifying areas of eloquent cortex. These advances are improving our ability to noninvasively detect epileptogenic foci which have gone undetected in the past and whose accurate localization is crucial for a favorable outcome following surgical resection

The effects of weaning methods on gut microbiota composition and horse physiology

Weaning has been described as one of the most stressful events in the life of horses. Given the importance of the interaction between the gut-brain axis and gut microbiota under stress, we evaluated (i) the effect of two different weaning methods on the composition of gut microbiota across time and (ii) how the shifts of gut microbiota composition after weaning affect the host. A total of 34 foals were randomly subjected to a progressive (P) or an abrupt (A) weaning method. In the P method, mares were separated from foals at progressively increasing intervals every day, starting from five min during the fourth week prior to weaning and ending with 6 h during the last week before weaning. In the A method, mares and foals were never separated prior to weaning (0 d). Different host phenotypes and gut microbiota composition were studied across 6 age strata (days -30, 0, 3, 5, 7, and 30 after weaning) by 16S rRNA gene sequencing. Results revealed that the beneficial species belonging to Prevotella, Paraprevotella, and Ruminococcus were more abundant in the A group prior to weaning compared to the P group, suggesting that the gut microbiota in the A cohort was better adapted to weaning. Streptococcus, on the other hand, showed the opposite pattern after weaning. Fungal loads, which are thought to increase the capacity for fermenting the complex polysaccharides from diet, were higher in P relative to A. Beyond the effects of weaning methods, maternal separation at weaning markedly shifted the composition of the gut microbiota in all foals, which fell into three distinct community types at 3 days post-weaning. Most genera in community type 2 (i.e., Eubacterium, Coprococcus, Clostridium XI, and Blautia spp.) were negatively correlated with salivary cortisol levels, but positively correlated with telomere length and N-butyrate production. Average daily gain was also greater in the foals harboring a community type 2 microbiota. Therefore, community type 2 is likely to confer better stress response adaptation following weaning. This study identified potential microbial biomarkers that could predict the likelihood for physiological adaptations to weaning in horses, although causality remains to be addressed

Neoadjuvant chemotherapy for patients with locally advanced vulvar cancer

PURPOSE OF REVIEW: Studies on treatment options for patients with locally advanced vulvar cancer (LAVC) are scarce, and high-level evidence for a primary treatment choice is lacking. Furthermore, current treatment options are associated with extensive morbidity and high complication rates. More effective treatment options are urgently needed. This review describes current treatment possibilities, focusing on literature regarding neoadjuvant chemotherapy (NACT) followed by surgery. RECENT FINDINGS: Although data are heterogeneous and limited, NACT followed by surgery might be an effective and well tolerated treatment alternative associated with lower morbidity compared with current treatment options, such as excenterative surgery or definitive chemoradiation. SUMMARY: Up until now, several studies describe an overall response rate of 40-86%. Surgery turned out to be possible in 40-90% of the LAVC patients who received NACT. Prospective studies on the efficacy and safety of NACT followed by surgery with a homogeneous chemotherapy regimen are urgently awaited. NACT should, at this point, still be considered investigational

Versican expression is associated with tumor-infiltrating CD8-positive T cells and infiltration depth in cervical cancer

Cervical carcinoma is the second most frequent cancer type in women worldwide. Both inflammatory cells and stromal cells are important for tumor progression. Stromal cells produce growth factors and extracellular matrix and provide an adequate environment for angiogenesis. Versican, a member of the extracellular matrix, has been shown to have a role in tumor progression. The aim of this study was to investigate versican expression, and its association with tumor-infiltrating inflammatory cell subsets and with clinicopathological parameters in human cervical cancers. We have studied the expression of versican in 149 cervical cancers using immunohistochemistry and mRNA in situ hybridization. Versican was predominantly expressed in the stroma (myofibroblasts). Using quantitative real-time-PCR, V0 was found to be the most prominent isoform. High stromal versican expression was significantly associated with a low number of tumor-infiltrating T cells (P=0.018) and particularly a low number of CD8-positive T cells (cytotoxic T cells; P=0.002). Stromal versican expression was significantly higher in patients with an infiltration depth > 14mm (P=0.004) and in patients with parametrial invasion (P=0.044). Stromal versican expression was not associated with survival. Our results suggest that versican expression in the stromal compartment of cervical cancers results in reduced numbers of intraepithelial CD8-positive T cells and enhanced local invasion. Modern Pathology (2010) 23, 1605-1615; doi:10.1038/modpathol.2010.154; published online 20 August 201

Intercomparison of ethanol, formaldehyde and acetaldehyde measurements from a flex-fuel vehicle exhaust during the WLTC

An intercomparison exercise of the world-harmonized light-duty vehicle test procedure (WLTP) aiming at measuring ethanol, formaldehyde and acetaldehyde emissions from a flex-fuel light-duty vehicle using E85 was conducted in the Vehicle Emission Laboratory (VELA) at the European Commission Joint Research Centre (EC-JRC), Ispra, Italy. The instruments used during the intercomparison allowed online measurements of these compounds directly from the diluted exhaust. Measurements were done either in real time or immediately after the test. The measurement and analysis of exhaust emissions over the world-harmonized light-duty vehicle test cycle was done by means of Fourier transform infrared spectroscopy (FTIR), proton transfer reaction-mass spectrometry (PTR-Qi-ToF-MS), photoacoustic spectroscopy (PAS) and gas chromatography (GC). Results showed that online systems can perform measurements from the vehicle diluted exhaust assuring a good repeatability (within instrument variance) and reproducibility (between instrument variance) of the results. Measurements from all the instruments were in good agreement (|Z-score| < 2). Results showed that online systems can perform measurements from the vehicle diluted exhaust assuring the reproducibility and repeatability of the results. Results obtained measuring at the tailpipe using a FTIR were in good agreement with those acquired measuring at the constant volume sampler (CVS). Considering the low sensitivity of the current technique used to measure hydrocarbons emissions towards oxygenated compounds (flame ionization detector; FID), non-methane organic gases (NMOG) were calculated applying their FID response factors to the measured emissions of ethanol, acetaldehyde and formaldehyde. NMOG resulted to be up to 74% higher than measured non-methane hydrocarbons (NMHC)

Intercomparison of ethanol, formaldehyde and acetaldehyde measurements from a flex-fuel vehicle exhaust over the WLTC

An intercomparison exercise of the world-harmonized light-duty vehicle test procedure (WLTP) aiming at measuring ethanol, formaldehyde and acetaldehyde emissions from a flex-fuel light-duty vehicle using E85 was conducted in the Vehicle Emission Laboratory (VELA) at the European Commission Joint Research Centre (EC-JRC), Ispra, Italy. The instruments used during the intercomparison allowed online measurements of these compounds directly from the diluted exhaust. Measurements were done either in real time or immediately after the test. The measurement and analysis of exhaust emissions over the world-harmonized light-duty vehicle test cycle was done by means of Fourier transform infrared spectroscopy (FTIR), proton transfer reaction-mass spectrometry (PTR-Qi-ToF-MS), photoacoustic spectroscopy (PAS) and gas chromatography (GC). Results showed that online systems can perform measurements from the vehicle diluted exhaust assuring a good repeatability (within instrument variance) and reproducibility (between instrument variance) of the results. Measurements from all the instruments were in good agreement (|Z-score| < 2). Results showed that online systems can perform measurements from the vehicle diluted exhaust assuring the reproducibility and repeatability of the results. Results obtained measuring at the tailpipe using a FTIR were in good agreement with those acquired measuring at the constant volume sampler (CVS). Considering the low sensitivity of the current technique used to measure hydrocarbons emissions towards oxygenated compounds (flame ionization detector; FID), non-methane organic gases (NMOG) were calculated applying their FID response factors to the measured emissions of ethanol, acetaldehyde and formaldehyde. NMOG resulted to be up to 74% higher than measured non-methane hydrocarbons (NMHC).JRC.C.4-Sustainable Transpor

EMMPRIN-induced MMP-2 activation cascade in human cervical squamous cell carcinoma

Tumor progression and recurrence of cervical cancer is associated with upregulation of matrix metalloproteinase 2 (MMP-2). We evaluated the location, origin, and activity of MMP-2 in cervical squamous cell carcinomas in comparison with MT1-MMP (MMP-14), TIMP-2 and EMMPRIN. Positive immuno-staining for MMP-2 in malignant cells was detected in 83% of the patients. Two patterns of tumor cell MMP-2 staining were observed: Either homogenous in all tumor cells or confined to the cells neighboring the stroma (tumor-border staining pattern, TBS). Fluorescence in situ zymography showed active MMP 2 mainly around tumor nodules displaying TBS. The MMP-2 staining of TBS tumors correlated significantly with the presence of TIMP 2 and MT1-MMP, proteins involved in docking MMP-2 to the cell surface, essential for MMP-2 activation. In situ mRNA hybridization in TBS tumors demonstrated more abundant presence of MMP-2 mRNA in neighboring myofibroblasts than in the adjacent tumor cells. Moreover, the TBS MMP-2 pattern correlated with the presence of EMMPRIN (P=0.023), suggesting that tumor cells induce MMP-2 production in nearby stromal cells. This pro-MMP-2 could subsequently be activated on tumor cells via the presence of MT1-MMP and TIMP-2. The biological relevance of this locally activated MMP-2 was underscored by the observation that only the TBS pattern of MMP-2 significantly correlated with decreased survival. In conclusion, the co-localization of EMMPRIN, MT1-MMP and TIMP-2 in human cervical carcinomas seems to be involved in a specific distribution pattern of tumor cell bound MMP-2, which is related with local proteolytic activity and therefore might be associated with worse prognosis of the patients