Genetic characterization of G3 rotaviruses detected in Italian children in the years 1993–2005

In recent years an apparent increase in the frequency of detection of G3P[8] rotaviruses has been observed worldwide. Similarly, in Italy G3P[8] strains have been detected sporadically and in a scattered fashion over 20 years, whereas in 2003 and 2005 G3P[8] rotavirus activity increased markedly. By analysis of the VP7, VP4, VP6, and NSP4 genes of a selection of G3P[8] rotaviruses detected between 1993 and 2005, a remarkable sequence conservation was observed in the VP7, VP4, and VP6 genes. By converse, after 2002 the Italian G3P[8] strains were found to possess unique mutations in significant regions of the NSP4 protein. J. Med. Virol. 81:2089–2095, 2009. © 2009 Wiley‐Liss, Inc.     

Emerging GII.4 norovirus variants affect children with diarrhea in Palermo,Italy in 2006

Although the genetic/antigenic heterogeneity of human noroviruses (NoVs) is impressive, a few genogroup II strains of genotype 4 (GII.4) are dominant worldwide. GII.4 NoVs evolve rapidly and in the last 15 years six epidemic variants have been identified. In 2005–2006, surveillance of sporadic viral gastroenteritis in children in Palermo, Italy, resulted in the detection of NoV strains in 20.9% of the patients admitted to hospital. By restriction fragment length polymorphism (RFLP) and sequence analysis of region A in the RNA‐dependent RNA‐polymerase (RdRp) gene, 59 NoV strains were successfully characterized. Eighty‐one percent of the strains were characterized as GII.4, 14% as GIIb/Hilversum and 5% as GI.1. Phylogenetic analysis of region A and of the ORF1/ORF2 overlapping region of the GII.4 strains recovered in Palermo in the years 2002–2006 revealed the sequential emergence of four variants, GII.4 2002, 2004, 2006a, and 2006b. The variant GII.4 2006a was detected in June and July, 2006, while the variant 2006b first appeared in August, 2006, becoming predominant thereafter. Based on these findings, the dynamics of replacement and circulation of the GII.4 NoV variants in Italy in 2005–2006 appear to have matched the temporal pattern observed in Europe during the same period. J. Med. Virol. 81:139–145, 2009. © 2008 Wiley‐Liss, Inc.     

Activity and resistance of trastuzumab according to different clinical settings

Trastuzumab, a humanized monoclonal antibody directed against HER2, has shown efficacy in breast cancers; however many patients do not respond to this reagent. Here, we discuss the potential mechanisms of trastuzumab efficacy and resistance in different clinical settings as a step toward optimizing the appropriate application of this antibody. The three major antitumor mechanisms of trastuzumab, i.e., inhibition of proliferation, antibody-dependent cell cytotoxicity (ADCC) and inhibition of DNA repair, appear to be differentially operative in different clinical settings. ADCC appears to be the prevalent mechanism in trastuzumab neoadjuvant monotherapy, whereas in neoadjuvant, adjuvant or metastatic settings in which trastuzumab is combined with chemotherapy, the relative role of ADCC is probably small, considering the compromising effects of chemotherapy on the immune cells that mediate this mechanism. In neoadjuvant and adjuvant settings involving concomitant use of trastuzumab and chemotherapy, the primary mechanism at play is presumably inhibition of DNA repair by the antibody, while in sequential protocols, the antibody acts mostly by exerting cytostatic activity through inhibition of HER2-mediated tumor cell proliferation. According to the ability of the antibody to induce cytotoxic or cytostatic antitumor effects depending on the clinical setting, different criteria, i.e., RECIST for cytotoxic effect, OS, and DFS for cytostatic, must be considered in accurately estimating antibody efficacy. Moreover, since trastuzumab resistance likely depends directly on the mechanisms responsible for its antitumor activity, resistance mechanisms must also be considered with respect to the different clinical settings.     

An adjusted EuroSCORE model for high-risk cardiac patients

Objective: To verify the accuracy and precision of the logistic European system for cardiac operative risk evaluation (EuroSCORE) in high-risk cardiac surgery patients and to develop and externally validate a new system of recalibration. Methods: The development series included 4279 high-risk patients who had undergone cardiac operations at the IRCCS Policlinico S. Donato. Performance, accuracy, and precision of the logistic EuroSCORE were assessed in this series, using a deciles-based comparison between expected and observed mortality rates, a receiver operating characteristic analysis, and a Hosmer–Lemeshow test for calibration. Differences between predicted and observed mortality rates were mathematically evaluated to develop an adjusted logistic EuroSCORE. This adjusted risk score was subsequently validated with the same approach on an external series of 1459 high-risk patients who had undergone cardiac operations at the Siena hospital. Results: The adjusted logistic EuroSCORE was based on five different correction factors applied to the crude logistic EuroSCORE depending on its value. At the external validation, this model provided a good performance, with observed mortality rates not significantly different from the expected in 8 out of 10 deciles of risk distribution. The adjusted EuroSCORE had the same moderate balanced accuracy of the crude logistic EuroSCORE (area under the curve: 0.695), with a better precision (Hosmer–Lemeshow calibration test: χ²: 3.6, p = 0.891). Conclusions: Recalibration of the logistic EuroSCORE in high-risk patients is needed due to its tendency to overestimate the mortality risk. The application of a variable correction factor results in a better performance, increased precision, with unaltered balanced accuracy.     

Comparison of different cortical connectivity estimators for high-resolution EEG recordings

The aim of this work is to characterize quantitatively the performance of a body of techniques in the frequency domain for the estimation of cortical connectivity from high-resolution EEG recordings in different operative conditions commonly encountered in practice. Connectivity pattern estimators investigated are the Directed Transfer Function (DTF), its modification known as direct DTF (dDTF) and the Partial Directed Coherence (PDC). Predefined patterns of cortical connectivity were simulated and then retrieved by the application of the DTF, dDTF, and PDC methods. Signal-to-noise ratio (SNR) and length (LENGTH) of EEG epochs were studied as factors affecting the reconstruction of the imposed connectivity patterns. Reconstruction quality and error rate in estimated connectivity patterns were evaluated by means of some indexes of quality for the reconstructed connectivity pattern. The error functions were statistically analyzed with analysis of variance (ANOVA). The whole methodology was then applied to high-resolution EEG data recorded during the well-known Stroop paradigm. Simulations indicated that all three methods correctly estimated the simulated connectivity patterns under reasonable conditions. However, performance of the methods differed somewhat as a function of SNR and LENGTH factors. The methods were generally equivalent when applied to the Stroop data. In general, the amount of available EEG affected the accuracy of connectivity pattern estimations. Analysis of 27 s of nonconsecutive recordings with an SNR of 3 or more ensured that the connectivity pattern could be accurately recovered with an error below 7% for the PDC and 5% for the DTF. In conclusion, functional connectivity patterns of cortical activity can be effectively estimated under general conditions met in most EEG recordings by combining high-resolution EEG techniques, linear inverse estimation of the cortical activity, and frequency domain multivariate methods such as PDC, DTF, and dDTF.     

Donepezil effects on sources of cortical rhythms in mild Alzheimer's disease: Responders vs. Non-Responders

Acetylcholinesterase inhibitors (AChEI) such as donepezil act in mild Alzheimer's disease (AD) by increasing cholinergic tone. Differences in the clinical response in patients who do or do not benefit from therapy may be due to different functional features of the central neural systems. We tested this hypothesis using cortical electroencephalographic (EEG) rhythmicity. Resting eyes-closed EEG data were recorded in 58 mild AD patients (Mini Mental State Examination [MMSE] range 17-24) before and approximately 1 year after standard donepezil treatment. Based on changes of MMSE scores between baseline and follow-up, 28 patients were classified as "Responders" (MMSEvar >or=0) and 30 patients as "Non-Responders" (MMSEvar <0). EEG rhythms of interest were delta (2-4 Hz), theta (4-8 Hz), alpha 1 (8-10.5 Hz), alpha 2 (10.5-13 Hz), beta 1 (13-20 Hz), and beta 2 (20-30 Hz). Cortical EEG sources were studied with low-resolution brain electromagnetic tomography (LORETA). Before treatment, posterior sources of delta, alpha 1 and alpha 2 frequencies were greater in amplitude in Non-Responders. After treatment, a lesser magnitude reduction of occipital and temporal alpha 1 sources characterized Responders. These results suggest that Responders and Non-Responders had different EEG cortical rhythms. Donepezil could act by reactivating existing yet functionally silent cortical synapses in Responders, restoring temporal and occipital alpha rhythms.     

Recognition of imagined hand movements with low resolution surface Laplacian and linear classifiers.

EEG-based Brain Computer Interfaces (BCIs) require on-line detection of mental states from spontaneous EEG signals. In this framework, it was suggested that EEG patterns can be better detected with EEG data transformed with Surface Laplacian computation (SL) than with the unprocessed raw potentials. However, accurate SL estimates require the use of many EEG electrodes, when local estimation methods are used. Since BCI devices have to use a limited number of electrodes for practical reasons, we investigated the performances of spline methods for SL estimates using a limited number of electrodes (low resolution SL). Recognition of mental activity was attempted on both raw and SL-transformed EEG data from five healthy people performing two mental tasks, namely imagined right and left hand movements. Linear classifiers were used including Signal Space Projection (SSP) and Fisher's linear discriminant. Results showed an acceptable average correlation between the waveforms obtained with the low resolution SL and these obtained with the SL computed from 26 electrodes (full resolution SL). More importantly, satisfactorily recognition scores for mental EEG-patterns were obtained with the low-resolution surface Laplacian transformation of the recorded potentials when compared with those obtained by using full resolution SL (82%). These results demonstrated also the utility of linear classifiers for the detection of mental patterns in the BCI field.