Multivariate analysis of brain metabolism reveals chemotherapy effects on prefrontal cerebellar system when related to dorsal attention network

BACKGROUND: Functional brain changes induced by chemotherapy are still not well characterized. We used a novel approach with a multivariate technique to analyze brain resting state [(18) F]FDG-PET in patients with lymphoma, to explore differences on cerebral metabolic glucose rate between chemotherapy-treated and non-treated patients. METHODS: PET/CT scan was performed on 28 patients, with 14 treated with systemic chemotherapy. We used a support vector machine (SVM) classification, extracting the mean metabolism from the metabolic patterns, or networks, that discriminate the two groups. We calculated the correct classifications of the two groups using the mean metabolic values extracted by the networks. RESULTS: The SVM classification analysis gave clear-cut patterns that discriminate the two groups. The first, hypometabolic network in chemotherapy patients, included mostly prefrontal cortex and cerebellar areas (central executive network, CEN, and salience network, SN); the second, which is equal between groups, included mostly parietal areas and the frontal eye field (dorsal attention network, DAN). The correct classification membership to chemotherapy or not chemotherapy-treated patients, using only one network, was of 50% to 68%; however, when all the networks were used together, it reached 80%. CONCLUSIONS: The evidenced networks were related to attention and executive functions, with CEN and SN more specialized in shifting, inhibition and monitoring, DAN in orienting attention. Only using DAN as a reference point, indicating the global frontal functioning before chemotherapy, we could better classify the subjects. The emerging concept consists in the importance of the investigation of brain intrinsic networks and their relations in chemotherapy cognitive induced changes

Chemotherapy effects on brain glucose metabolism at rest

Background: A growing number of studies reports that chemotherapy may impair brain functions inducing cognitive changes which can persist in a subset of cancer survivors. Aims: To investigate the neural basis of the chemotherapy-induced neurobehavioral changes by means of metabolic imaging and voxel-based statistical parametric mapping analyses. Methods: We studied the resting brain [18]FDG-PET/CT images of 43 adult cancer patients with solid (n=12, 28%) or hematologic malignancies (n=31, 72%); 12 patients were studied prior to chemotherapy (No chemotherapy) while treated patients were divided into two matched subgroups: Early High (6 chemotherapy cycles, n=10), and Late Low (>9 months after chemotherapy, <6 chemotherapy cycles, n=21). Findings: Compared to No chemotherapy, the Early High subgroup showed a significant bilateral (p<0.05) lower regional cerebral metabolic rate of glucose metabolism in both the prefrontal cortices and white matter, cerebellum, posterior medial cortices and limbic regions. A similar pattern emerged in the Early High versus Low Late comparison, while no significant result was obtained in the Low Late versus No chemotherapy comparison. The number of cycles and the post-chemotherapy time were negatively and positively correlated, respectively, with a set of these same brain regions. Interpretation: The present study shows that chemotherapy induces significant transient changes in the glucose metabolism of multiple cerebral cortical and white matter regions with a prevailing involvement of the prefrontal cortex. The severity of these changes are significantly related with the number of chemotherapy cycles and a subset of brain regions seems to present longer lasting, but more subtle, metabolic changes

The CDC42-Interacting Protein 4 Controls Epithelial Cell Cohesion and Tumor Dissemination

SummaryThe role of endocytic proteins and the molecular mechanisms underlying epithelial cell cohesion and tumor dissemination are not well understood. Here, we report that the endocytic F-BAR-containing CDC42-interacting protein 4 (CIP4) is required for ERBB2- and TGF-β1-induced cell scattering, breast cancer (BC) cell motility and invasion into 3D matrices, and conversion from ductal breast carcinoma in situ to invasive carcinoma in mouse xenograft models. CIP4 promotes the formation of an E-cadherin-CIP4-SRC complex that controls SRC activation, E-cadherin endocytosis, and localized phosphorylation of the myosin light chain kinase, thereby impinging on the actomyosin contractility required to generate tangential forces to break cell-cell junctions. CIP4 is upregulated in ERBB2-positive human BC, correlates with increased distant metastasis, and is an independent predictor of poor disease outcome in subsets of BC patients. Thus, it critically controls cell-cell cohesion and is required for the acquisition of an invasive phenotype in breast tumors

A multidisciplinary approach to estimating wolf population size for long-term conservation

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Armida disvelata. L’immagine del velo nella "Gerusalemme liberata"

The essay takes into account the different occurrences of the term ‘veil’ in the Gerusalemme liberata. After an analysis of the metaphorical meanings of the term, the focus moves towards the veils that hide or embellish some of the female characters, in particular Sofronia, Erminia and Armida, bringing to light the different functions – even symbolic – that appear to be connected to this garment.The essay takes into account the different occurrences of the term ‘veil’ in the Gerusalemme liberata. After an analysis of the metaphorical meanings of the term, the focus moves towards the veils that hide or embellish some of the female characters, in particular Sofronia, Erminia and Armida, bringing to light the different functions – even symbolic – that appear to be connected to this garment

Characterization of gait maturation using frequency domain analysis of CoM acceleration

Introduction: The use of inertial sensors, placed at approximately CoM level (L5 level), is today a common practice in gait analysis [1]: CoM acceleration data allow indeed evaluating spatio-temporal gait parameters [2] and characterizing different populations [3]. Frequency domain analysis of the CoM acceleration signal has been already proposed in literature, in order to assess the range of frequency spectrum and its dependency on the motor task [4\u20136] or in order to evaluate characteristics of the signal in relation to task event (e.g. impact-related shock, Parkinson's freezing) [7,8]. The aim of this study was to investigate the use of the frequency domain analysis of CoM acceleration in characterizing gait maturation from childhood to adulthood, evidencing deterioration of gait performance during ageing. Methods: The study was conducted on: 7 toddlers at two weeks of walking experience (T2wks, 13 \ub1 2 mo, 10 \ub1 2 kg, 78 \ub1 4 cm), 7 toddlers at 6 months of walking experience (T6mo, 18 \ub1 2 mo, 11 \ub1 2 kg, 82 \ub1 2 cm), 7 4-year old children (4YC, 4 y, 16 \ub1 2 kg, 101 \ub1 3 cm), 7 6-year old children (6YC, 6 y, 23 \ub1 1 kg, 121 \ub1 2 cm), 7 adolescents (15YA, 15 y, 60 \ub1 13 kg, 162 \ub1 6 cm), 7 young adults (25YA, 25 \ub1 1 y, 171 \ub1 9 cm, 67 \ub1 14 kg) and 7 elderlies (E, 75 \ub1 7 y, 77 \ub1 11 kg, 167 \ub1 6 cm). The participants performed an instrumented over ground gait task wearing a tri-axial wireless inertial sensors (OPALS, Apdm, USA) (fs 128 Hz) located on L5. Ten consecutive strides, for all the participants, were analyzed [9]. The FFT of the acceleration signals was used to determine the frequency corresponding to the maximum of the monolateral signal spectrum (fMAX). The signal power (PW) was calculated integrating the potential spectrum density (psd), obtained with the Matlab built-in function pwelch. Then PW was normalized with the maximum value of it, obtaining the normalized signal power (PW%). The frequencies corresponding to the 50% (f50%) and 98% (f98%) of the PW%. were calculated. fMAX, f50% and f98% were calculated along the three axes (AP, ML V). The estimated parameters were tested with gaussianity test in such way was possible performed the right statistical analysis: Kruskal\u2013Wallis test with a p-value of 5%. When age effect was found, a multiple comparison test was performed. Results: Kruskal\u2013Wallis results showed effect of age on all the features in V direction and on f98% and f50% in AP direction. No significant results were found in ML direction. In Fig. 1a and b are showed 25\ub0 50\ub0 and 75\ub0 percentiles of fMAX_AP and fMAX_V respectively. Colours indicate differences found by the multiple comparison test for T2wks group (blue): red indicates statistical differences and grey no statistical differences. Fig. 1 Download high-res image (67KB)Download full-size image Fig. 1. Discussion: The results of the present work indicate that f50%, f98% and fMAX can be relevant and descriptive parameters of gait development. In particular, fMAX_AP, changes from high to low values with the increasing of the age and could describe improvement and deterioration of the motor development; moreover fMAX_V and f98%_V discern between immature and mature gait during gait development and could be used as an index of deterioration of gait performance during ageing