Data_Sheet_1_Default Mode Network Structural Integrity and Cerebellar Connectivity Predict Information Processing Speed Deficit in Multiple Sclerosis.PDF

<p>Cognitive impairment affects about 50% of multiple sclerosis (MS) patients, but the mechanisms underlying this remain unclear. The default mode network (DMN) has been linked with cognition, but in MS its role is still poorly understood. Moreover, within an extended DMN network including the cerebellum (CBL-DMN), the contribution of cortico-cerebellar connectivity to MS cognitive performance remains unexplored. The present study investigated associations of DMN and CBL-DMN structural connectivity with cognitive processing speed in MS, in both cognitively impaired (CIMS) and cognitively preserved (CPMS) MS patients. 68 MS patients and 22 healthy controls (HCs) completed a symbol digit modalities test (SDMT) and had 3T brain magnetic resonance imaging (MRI) scans that included a diffusion weighted imaging protocol. DMN and CBL-DMN tracts were reconstructed with probabilistic tractography. These networks (DMN and CBL-DMN) and the cortico-cerebellar tracts alone were modeled using a graph theoretical approach with fractional anisotropy (FA) as the weighting factor. Brain parenchymal fraction (BPF) was also calculated. In CIMS SDMT scores strongly correlated with the FA-weighted global efficiency (GE) of the network [GE(CBL-DMN): ρ = 0.87, R² = 0.76, p < 0.001; GE(DMN): ρ = 0.82, R² = 0.67, p < 0.001; GE(CBL): ρ = 0.80, R² = 0.64, p < 0.001]. In CPMS the correlation between these measures was significantly lower [GE(CBL-DMN): ρ = 0.51, R² = 0.26, p < 0.001; GE(DMN): ρ = 0.48, R² = 0.23, p = 0.001; GE(CBL): ρ = 0.52, R² = 0.27, p < 0.001] and SDMT scores correlated most with BPF (ρ = 0.57, R² = 0.33, p < 0.001). In a multivariable regression model where SDMT was the independent variable, FA-weighted GE was the only significant explanatory variable in CIMS, while in CPMS BPF and expanded disability status scale were significant. No significant correlation was found in HC between SDMT scores, MRI or network measures. DMN structural GE is related to cognitive performance in MS, and results of CBL-DMN suggest that the cerebellum structural connectivity to the DMN plays an important role in information processing speed decline.</p

NMR as Evaluation Strategy for Cellular Uptake of Nanoparticles

Advanced nanostructured materials, such as gold nanoparticles, magnetic nanoparticles, and multifunctional materials, are nowadays used in many state-of-the-art biomedical application. However, although the engineering in this field is very advanced, there remain some fundamental problems involving the interaction mechanisms between nanostructures and cells or tissues. Here we show the potential of ¹H NMR in the investigation of the uptake of two different kinds of nanostructures, that is, maghemite and gold nanoparticles, and of a chemotherapy drug (Temozolomide) in glioblastoma tumor cells. The proposed experimental protocol provides a new way to investigate the general problem of cellular uptake for a variety of biocompatible nanostructures and drugs

Cancer cell culture.

<p>The figure shows the untreated cells (a) and MNs-treated cells (b-d) observed after 24 h. Prussian Blue evidences the iron depots. Enlargement: a>50 µm, b>10 µm, c>10 µm and d>10 µm.</p

TEM of MNs.

<p>Panel a shows the organization of MNs in chains in the bacteria (scale bar, 500 nm). Panels b-c show that the typical conformation of chains is maintained after isolation of MNs. Scale bars: b>200 nm, c>100 nm. Panel d, X-ray microanalysis shows the iron content of the MNs.</p

MR Images of representative animals.

<p>A) MRI Upper line: animal treated with MNs injection; images acquired before MNs injection (a), 24 h (b), one week (c) and two weeks (d) after MNs injection. Second line: animal treated with MNs injection with AMF; images acquired before MNs injection (e), 24 h (f), one week (g) and two weeks (h) after MNs injection. Magnetosomes are injected in tumor mass and MRI allows the detection of injection sites (white stars). B) animal treated with AMF; images acquired before 24 h (i), one week (l) and two weeks (m) after treatment. Control animal not treated with MNs and AMF; images acquired after two weeks (n).</p

Thermal properties of MNs in alternate magnetic field.

<p>Variation of temperature of samples containing: (a) 6.7 mg of MNs lyophilized and (b) MNs diluted in distilled water at concentration of: 3 mg/ml, 2 mg/ml, 1 mg/ml, 0.5 mg/ml exposed to an AMF of 187 kHz (23kA/m) as a function of time, measured by infrared camera.</p

Susceptibility measurement.

<p>DC susceptibility measurements performed on a freeze-dried magnetosomes sample: (a) hysteresis loops at high (300 K) and low (2 K) temperature and (b) Zero Field-Cooled/Field-Cooled (ZFC/FC) curves collected at low field, H = 50 Oe.</p

TEM shows the internalization of chains of MNs in HT-29 cancer cells.

<p>The chains that have penetrated in the cells are composed by 6-10 units of MNs and are positioned near the nucleus (Panel a). In Panel b, MNs are visible at cell membrane (arrows) or in the Golgi complex. Panel c shows the localization of the MNs in cytoplasmic vacuoles at high enlargement (Scale bars, a 2 µm, b 1 µm, c 120 nm, d 10 µm). Panel d shows a representative SEM image of HT-29 cancer cell (0.2 mg/ml MNs 12 h); no appreciable alterations of the surface are visible when compared to controls.</p

Histological analysis of tumors.

<p>In the Panel A-C histology of tumor of the experimental group is showed. Injection site is showed in Panel A while in Panel B the living tumor area is illustrated. In the Panel C injured tumor area is showed. In Panel E-F histology of first subgroup of the control group is presented. In Panel G-I histology of second subgroup of the control group is presented and in the Panel L-N is showed the third subgroup of the control group. The presence of MNs depots is detectable in injection sites (A). MNs are capable to migrate and spread in tumor tissue causing the formation of fibrotic and necrotic areas (B, C). Scale bars, A-C 60 µm, D-E 300 µm, F and G 120 µm, H-I 60 µm, I 300 µm, M 120 µm, N 60 µm. Legend: m = MNs, n =  necrosis and t  =  tumor.</p

Investigation on NMR Relaxivity of Nano-Sized Cyano-Bridged Coordination Polymers

We present the first comparative investigation of the Nuclear Magnetic Resonance (NMR) relaxivity of a series of nanosized cyano-bridged coordination networks stabilized in aqueous solution. These Ln³⁺/[Fe­(CN)₆]^3‑ (Ln = Gd, Tb, Y) and M²⁺/[Fe­(CN)₆]^3‑ (M = Ni, Cu, Fe) nanoparticles with sizes ranging from 1.4 to 5.5 nm are stabilized by polyethylene glycols (MW = 400 or 1000), polyethylene glycol functionalized with amine groups (MW = 1500), or by N-acetyl-d-glucosamine. The evaluation of NMR relaxivity allowed estimation of the Magnetic Resonance Imaging (MRI) contrast efficiency of our systems. The results demonstrate that Gd³⁺/[Fe­(CN)₆]^3‑ nanoparticles have <i>r</i>_1p and <i>r</i>_2p relaxivities about four times higher than the values observed in the same conditions for the commercial Contrast Agents (CAs) ProHance or Omniscan, regardless of the stabilizing agent used, while nanoparticles of Prussian blue and its analogues M²⁺/[Fe­(CN)₆]^3‑ (M = Ni, Cu, Fe) present relatively modest values. The influence of the chemical composition of the nanoparticles, their crystal structure, spin values of lanthanide and transition metal ions, and stabilizing agent on the relaxivity values are investigated and discussed