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Robot-mediated therapy is a viable approach for upper limb rehabilitation. The upper limb is a highly complex segment and the identification of the appropriate devices capable of rehabilitating it globally (from the shoulder to the hand) in clinical practice is crucial. In this work, we aimed: (i) to describe an approach used in identifying a set of technological and robotic devices to globally treat the upper limb, and (ii) to evaluate the feasibility of the identified set in clinical practice. Using an ad-hoc form, a multidisciplinary team identified a set of four robotic and sensor-based devices to treat globally the upper limb. Then, 30 stroke patients were enrolled and assigned to two groups: the robotic group (RG), where patients were treated with the robotic set, or the conventional group (CG). All patients were evaluated before and after the treatment. In the RG the patients used all the devices (one in each rehabilitation session), the treatment was well accepted, without drop-outs or adverse events. Using a multidisciplinary approach, we identified a set of technological and robotic devices to treat the upper limb globally, and then we experimented to ascertain its feasibility, in a pilot study. Robotics offers a considerable number of devices for rehabilitation that should be selected according to rehabilitation aims and feasibility in clinical practice.

Long-term motor deficits affect approximately two thirds of stroke survivors, reducing their quality of life. An effective rehabilitation therapy requires intense and repetitive training, which is resource demanding. Virtual Agents (VAs) and Socially Assistive Robots (SARs) offer high intensity, repetitive and reproducible therapy and are thus both promising as rehabilitation tools. In this paper, we compare a SAR and a VA during a rehabilitation task in terms of users’ engagement and movement performance, while leveraging neuroscientific methods to investigate potential differences at the neural level. Results show that our participants’ performance on the exercise was higher with a SAR than with a VA, which was especially clear under conditions of decreased perceptual information. Our participants reported higher levels of engagement with the SAR. Taken together, we provide evidence that SARs are a favorable alternative to VAs as rehabilitation tools.

The use of exosomes for diagnostic and disease monitoring purposes is becoming particularly appealing in biomedical research because of the possibility to study directly in biological fluids some of the features related to the organs from which exosomes originate. A paradigmatic example are brain-derived exosomes that can be found in plasma and used as a direct read-out of the status of the central nervous system (CNS). Inspired by recent remarkable development of plasmonic biosensors, we have designed a surface plasmon resonance imaging (SPRi) assay that, taking advantage of the fact that exosome size perfectly fits within the surface plasmon wave depth, allows the detection of multiple exosome subpopulations of neural origin directly in blood. By use of an array of antibodies, exosomes derived from neurons and oligodendrocytes were isolated and detected with good sensitivity. Subsequently, by injecting a second antibody on the immobilized vesicles, we were able to quantify the amount of CD81 and GM1, membrane components of exosomes, on each subpopulation. In this way, we have been able to demonstrate that they are not homogeneously expressed but exhibit a variable abundance according to the exosome cellular origin. These results confirm the extreme variability of exosome composition and demonstrate how SPRi can provide an effective tool for their characterization. Besides, our work paves the road toward more precise clinical studies on the use of exosomes as potential biomarkers of neurodegenerative diseases.

Here we describe a simple approach for the simultaneous detection of multiple microRNAs (miRNAs) using a single nanostructured reagent as surface plasmon resonance imaging (SPRi) enhancer and without using enzymatic reactions, sequence specific enhancers or multiple enhancing steps as normally reported in similar studies. The strategy involves the preparation and optimisation of neutravidin-coated gold nanospheres (nGNSs) functionalised with a previously biotinylated antibody (Ab) against DNA/RNA hybrids. The Ab guarantees the recognition of any miRNA sequence adsorbed on a surface properly functionalised with different DNA probes; at the same time, gold nanoparticles permit to detect this interaction, thus producing enough SPRi signal even at a low ligand concentration. After a careful optimisation of the nanoenhancer and after its characterisation, the final assay allowed the simultaneous detection of four miRNAs with a limit of detection (LOD) of up to 0.5 pM (equal to 275 attomoles in 500 μL) by performing a single enhancing injection. The proposed strategy shows good signal specificity and permits to discriminate wild-type, single- and triple-mutated sequences much better than non-enhanced SPRi. Finally, the method works properly in complex samples (total RNA extracted from blood) as demonstrated by the detection of four miRNAs potentially related to multiple sclerosis used as case study. This proof-of-concept study confirms that the approach provides the possibility to detect a theoretically unlimited number of miRNAs using a simple protocol and an easily prepared enhancing reagent, and may further facilitate the development of affordable multiplexing miRNA screening for clinical purposes., Research funding was provided by the Italian Ministry of Health within the framework of the European EuroNanoMedII Project (Call 2015) entitled “NanoPlasmiRNA”; DGA-FSE (Diputación General de Aragón–Fondo Social Europeo); Ministerio de Educación, Cultura y Deportes of Spanish Government, FPU grant (FPU014/06249).

Virtual reality for the treatment of motor impairment is a burgeoning application of digital technology in neurorehabilitation. Virtual reality systems pose an opportunity for health care providers to augment the dose of task-oriented exercises delivered both in the clinic, and via telerehabilitation models in the home. The technology is almost exclusively applied as an adjunct to traditional approaches and is typically characterized by the use of gamified exergames which feature task-oriented physiotherapy exercises. At present, evidence for the efficacy of this technology is sparse, with some reviews suggesting it is the same or no better than conventional approaches. The purpose of this article is to provide real-world insights on the adoption of a virtual reality by 3 European clinics in 3 different service delivery models. These include an inpatient setting for Parkinson disease, a kiosk model for pediatric neurorehabilitation, and a home-based telerehabilitation model for neurologic patients. Motivations, settings, requirements for the pathology, outcomes, and challenges encountered during this process are reported with the objective of priming clinicians on what to expect when implementing virtual reality in neurorehabilitation.

Extracellular vesicles (EVs) from mesenchymal stromal cells (MSC) are emerging as valuable therapeutic agents for tissue regeneration and immunomodulation, but their clinical applications have so far been limited by the technical restraints of current isolation and characterisation procedures. This study shows for the first time the successful application of Raman spectroscopy as label-free, sensitive and reproducible means of carrying out the routine bulk characterisation of MSC-derived vesicles before their use in vitro or in vivo, thus promoting the translation of EV research to clinical practice. The Raman spectra of the EVs of bone marrow and adipose tissue-derived MSCs were compared with human dermal fibroblast EVs in order to demonstrate the ability of the method to distinguish the vesicles of the three cytotypes automatically with an accuracy of 93.7%. Our data attribute a Raman fingerprint to EVs from undifferentiated and differentiated cells of diverse tissue origin, and provide insights into the biochemical characteristics of EVs from different sources and into the differential contribution of sphingomyelin, gangliosides and phosphatidilcholine to the Raman spectra themselves. Extracellular vesicles (EVs) from mesenchymal stromal cells (MSC) are emerging as valuable therapeutic agents for tissue regeneration and immunomodulation, but their clinical applications have so far been limited by the technical restraints of current isolation and characterisation procedures. This study shows for the first time the successful application of Raman spectroscopy as label-free, sensitive and reproducible means of carrying out the routine bulk characterisation of MSC-derived vesicles before their use in vitro or in vivo, thus promoting the translation of EV research to clinical practice. The Raman spectra of the EVs of bone marrow and adipose tissue-derived MSCs were compared with human dermal fibroblast EVs in order to demonstrate the ability of the method to distinguish the vesicles of the three cytotypes automatically with an accuracy of 93.7%. Our data attribute a Raman fingerprint to EVs from undifferentiated and differentiated cells of diverse tissue origin, and provide insights into the biochemical characteristics of EVs from different sources and into the differential contribution of sphingomyelin, gangliosides and phosphatidilcholine to the Raman spectra themselves.

Among polymeric nanoparticles designed for cancer therapy, PLGA nanoparticles have become one of the most popular polymeric devices for chemotherapeutic-based nanoformulations against several kinds of malignant diseases. Promising properties, including long-circulation time, enhanced tumor localization, interference with "multidrug" resistance effects, and environmental biodegradability, often result in an improvement of the drug bioavailability and effectiveness. In the present work, we have synthesized 1,7-bis(3,4-dimethoxyphenyl)-5-hydroxyhepta-1,4,6-trien-3-one (ASC-J9) and developed uniform ASC-J9-loaded PLGA nanoparticles of about 120 nm, which have been prepared by a single-emulsion process. Structural and morphological features of the nanoformulation were analyzed, followed by an accurate evaluation of the in vitro drug release kinetics, which exhibited Fickian law diffusion over 10 days. The intracellular degradation of ASC-J9-bearing nanoparticles within estrogen-dependent MCF-7 breast cancer cells was correlated to a time- and dose-dependent activity of the released drug. A cellular growth inhibition associated with a specific cell cycle G2/M blocking effect caused by ASC-J9 release inside the cytosol allowed us to put forward a hypothesis on the action mechanism of this nanosystem, which led to the final cell apoptosis. Our study was accomplished using Annexin V-based cell death analysis, MTT assessment of proliferation, radical scavenging activity, and intracellular ROS evaluation. Moreover, the intracellular localization of nanoformulated ASC-J9 was confirmed by a Raman optical imaging experiment designed ad hoc. PLGA nanoparticles and ASC-J9 proved also to be safe for a healthy embryo fibroblast cell line (3T3-L1), suggesting a possible clinical translation of this potential nanochemotherapeutic to expand the inherently poor bioavailability of hydrophobic ASC-J9 that could be proposed for the treatment of malignant breast cancer. © 2014 American Chemical Society.

We present here the surface-enhanced Raman spectroscopic (SERS)-based detection of the Wilm’s tumor gene (WT1) sequence using dye-labeled reporter oligonucleotide and magnetic core @ gold shell nanoparticles. Thiolated single-stranded DNA (ssDNA) complementers of the WT1 sequence were used to functionalize the gold shell with capture oligonucleotides in a facile and fast two-step method. The signal amplification performance of the core @ shell colloidal SERS substrate was tested using malachite green as label dye. The Raman signal enhancing efficacy of the magnetic core @ gold shell nanomaterial was compared with the efficacy of spherical gold particles produced using the conventional citrate reduction method. The core @ shell particles were found to be superior both regarding robustness in SERS and facile separation in a heterogeneous reaction system. The core @ shell particles functionalized with target specific oligonucleotide were able to capture the WT1 target and worked as Raman signal amplifiers in our assay system. The good physicochemical characteristics of these particles and the sensitivity observed in SERS experiments allow us to expect good performance in the further development steps of a novel, fast and reliable spectroscopic method for WT1 detection in minimal residual disease patients.

Paper-based SERS active substrates were prepared adsorbing spherical and star-shaped gold nanoparticles on a standard filter paper support. Besides the deposition conditions, morphological parameters of the particles were found to strongly affect the enhancer properties of the substrates. The developed substrate was tested regarding surface homogeneity as well as in the quantitative analysis of malachite green, - a well documented Raman reporter dye - and proved to be capable also to detect the oxidation products of apomorphine, a well-known drug molecule used in Parkinson's disease. This material is simple to prepare, easy to handle and dispose and as such it could be a perfect target for further development of a new family of mass-produced, cheap solid SERS substrates. © 2013 Elsevier B.V.

Gold nanorods are an important kind of nanoparticles characterized by peculiar plasmonic properties. Despite their widespread use in nanotechnology, the synthetic methods for the preparation of gold nanorods are still not fully optimized. In this paper we describe a new, highly efficient, two-step protocol based on the use of hydroquinone as a mild reducing agent. Our approach allows the preparation of nanorods with a good control of size and aspect ratio (AR) simply by varying the amount of hexadecyl trimethylammonium bromide (CTAB) and silver ions (Ag(+)) present in the "growth solution". By using this method, it is possible to markedly reduce the amount of CTAB, an expensive and cytotoxic reagent, necessary to obtain the elongated shape. Gold nanorods with an aspect ratio of about 3 can be obtained in the presence of just 50 mM of CTAB (versus 100 mM used in the standard protocol based on the use of ascorbic acid), while shorter gold nanorods are obtained using a concentration as low as 10 mM.

The detection of biomarkers by means of Surface Enhanced Raman Spectroscopy (SERS) is foreseen to became a very important tool in the clinical practice because of its excellent sensitivity and potential for the simultaneous detection of multiple biomarkers. In the present paper we describe how it was possible to build a sensor for the detection of genetic biomarkers involved in acute myeloid leukemia. The assay is based on the use of a specifically designed SERS substrate made of a 2D crystal structure of polymeric pillars embedded in a gold layer. This substrate is characterized by good enhancing properties coupled with an excellent homogeneity. The SERS substrate was conjugated with DNA probes complementary to a target sequence and used in a sandwich assay with gold nanoparticles labeled with a second DNA probe and a Raman reporter. The so developed assay allowed the detection of a leukemia biomarker (WT1 gene) and an housekeeping gene with low picomolar sensitivity. At last, we optimized the assay in order to tackle one of the main limitations of SERS based assay: the loss of signal that is observed when the Raman spectra are collected in liquid. Combining a preferential functionalization on the polymeric pillars with a different height of the polymer pillars from the gold layer the assay demonstrated its effectiveness even when measured in buffer.

Apomorphine (aporphine-10,11-diol, CA Registry Number 58004) is a non-narcotic derivative of morphine discovered in 1869 by Mattheisen1 and it is a well-known potent short-acting dopamine agonist at D1 and D2 dopamine receptors, typically used in the treatment of patients with advanced Parkinson's disease (PD). To identify the unknown vibrational spectrum of this compound, apomorphine bare salt and its commercial drug formulation (Apofin) were examined by means of Raman spectroscopy. In the Raman spectrum of apomorphine (both bare salt and commercial drug), two strong characteristic signals were found, which were assigned with the help of first-principles calculations: the band at 1589 cm−1 (assigned to the stretching mode of the B aromatic ring coupled with CH in-plane bending) and the band at 1302 cm−1 (assigned to O-H in-plane bending and CH2 twisting and wagging vibrations). Copyright © 2009 John Wiley & Sons, Ltd.

We present the first results of microstructure replica with re-usable masters in poly vinyl alcohol (PVA). Microneedles of heights ranging from 500 to 1100@mm were fabricated through double-exposure deep X-ray lithography (DXRL) process and successfully replicated. A single PVA master was used as a template to successfully replicate up to 10 PMMA microneedle arrays, suggesting that this method might be a possible alternative to PDMS processes. A preliminary characterization of the relationship between the surface roughness of the substrates and the force required for demoulding was also performed.

Electroencephalography (EEG) recordings can be used to help paralyzed patients by replacing functionality of damaged neural connections through the aid of a brain-computer interface. Conventional electrodes used for EEG require long skin preparation due to the impedance of the outermost layers of skin. On the contrary, dry spiked electrodes allow overcoming of impedance problems and can be suitable for long-term measurements. This paper describes microfabrication and packaging of micropatterned dry electrodes built with deep X-ray lithography, electroplating and soft lithography. Preliminary measurements performed with electrodes having different geometries are also described. (c) 2007 Elsevier B.V. All rights reserved.

In this article, we describe how it is possible to tune the size and the aspect ratio of gold nanorods obtained using a highly efficient protocol based on the use of hydroquinone as a reducing agent by varying the amounts of CTAB and silver ions present in the “seed-growth” solution. Our approach not only allows us to prepare nanorods with a four times increased Au3+ reduction yield, when compared with the commonly used protocol based on ascorbic acid, but also allows a remarkable reduction of 50–60 % of the amount of CTAB needed. In fact, according to our findings, the concentration of CTAB present in the seed-growth solution do not linearly influence the final aspect ratio of the obtained nanorods, and an optimal concentration range between 30 and 50 mM has been identified as the one that is able to generate particles with more elongated shapes. On the optimized protocol, the effect of the concentration of Ag+ ions in the seed-growth solution and the stability of the obtained particles has also been investigated.

Surface-enhanced Raman spectroscopy (SERS) widely improves the sensitivity of traditional Raman analysis, thus allowing this technique to be exploited for the development of new bio-analytical tests. In this work, 3D substrates made of zinc oxide tetrapods (ZnOTP) are decorated with branched gold nanoparticles by means of a new photochemical approach. The SERS enhancing properties of the obtained substrate are tested using different Raman dyes and apomorphine, a drug used for the management of Parkinson disease. The results prove that the enhancing properties depend on the shape of the gold nanoparticles grown on the branches of ZnO tetrapods. The optimized substrate here developed is characterized by an enhancing factor up to 7 x 10(6) and a detection limit for apomorphine of 1 mM. Finally, the new substrates are tested to study single cancer cells showing enhanced Raman signals related to the portion of the cell interacting with the 3D structure of the substrate.

Aims: Chronic lung allograft dysfunction represents the main cause of death after lung transplantation, and so far there is no effective therapy. Mesenchymal cells (MCs) are primarily responsible for fibrous obliteration of small airways typical of chronic lung allograft dysfunction. Here, we engineered gold nanoparticles containing a drug in the hydrophobic section to inhibit MCs, and exposing on the outer hydrophilic surface a monoclonal antibody targeting a MC-specific marker (half-chain gold nanoparticles with everolimus). Materials & methods: Half-chain gold nanoparticles with everolimus have been synthesized and incubated with MCs to evaluate the effect on proliferation and apoptosis. Results & discussion: Drug-loaded gold nanoparticles coated with the specific antibody were able to inhibit proliferation and induce apoptosis without stimulating an inflammatory response, as assessed by in vitro experiments. Conclusion: These findings demonstrate the effectiveness of our nanoparticles in inhibiting MCs and open new perspectives for a local treatment of chronic lung allograft dysfunction. Original submitted 24 July 2013; Revised submitted 15 October 2013

Surface Enhanced Raman Spectroscopy is a powerful analytical technique that combines the excellent chemical specificity of Raman spectroscopy with the good sensitivity provided by the enhancement of the signal observed when a molecule is located on (or very close to) the surface of suitable nanostructured metallic materials. The availability of cheap, reliable and easy to use SERS substrates would pave the road to the development of bioanalytical tests that can be used in clinical practice. SERS, in fact, is expected to provide not only higher sensitivity and specificity, but also the simultaneous and markedly improved detection of several targets at the same time with higher speed compared to the conventional analytical methods. Here, we present the SERS activity of 2-D plasmonic crystals made by polymeric pillars embedded in a gold matrix obtained through the combination of soft-lithography and plasma deposition techniques on a transparent substrates. The use of a transparent support material allowed us to perform SERS detection from support side opening the possibility to use these substrates in combination with microfluidic devices. In order to demonstrate the potentialities for bioanalytical applications, we used our SERS active gold surface to detect the oxidation product of apomorphine, a well-known drug molecule used in Parkinson’s disease which has been demonstrated being difficult to study by traditional HPLC based approaches.

Surface Enhanced Raman Spectroscopy (SERS) is a popular method in bio-analytical chemistry and a potentially powerful enabling technology for in vitro diagnostics. SERS combines the excellent chemical specificity of Raman spectroscopy with the good sensitivity provided by enhancement of the signal that is observed when a molecule is located on (or very close to) the surface of nanostructured metallic materials. Star-like gold nanoparticles (SGN) are a new class of multibranched nanoparticles that in the last few years have attracted the attention of SERS community for their plasmonic properties. In this work we present a new method to prepare star-like gold nanoparticles with a simple one step protocol at room temperature using hydroquinone as reducing agent. Besides we compare the enhancement of Raman signal of malachite green, a dye commonly employed as label in biological studies, by star-like gold nanoparticles having different size, directly in liquid. This study shows that SGN provide good enhancement of Raman signal and that the effect of their dimension is strongly dependent on the wavelength used. Moreover preliminary results suggest that SGN produced using this method are characterized by good physical-chemical properties and they can be functionalized using the standard thiol chemistry. Overall, these results suggest that star-like gold nanoparticles produced through this method could be used for the further development of highly specific and sensitive SERS-based bio-analytical tests. © 2013 Copyright SPIE.

Monitoring biosignals, such as in electrocardiography (ECG), electromiography (EMG) and electroencephalography (EEG), is important for a better understanding of the pathological and physiological conditions of human subjects. In clinical practice the recording of biopotentials is carried out in general with wet electrodes, considered as the golden standard, although they have shown some limits: (i) the susceptibility to motions artifacts, critical aspect in ECG and EMG monitoring, (ii) the time-consuming procedure to be applied in EEG examinations, and (iii) the inability to record biosignals in long-term applications. In the past years innovative solutions have been suggested, among which microstructured dry electrodes showed very promising features. This study represents a first technological assessment of a novel type of microneedles-based dry electrodes. In this paper it has been proved that these electrodes: (i) seem to allow a better electro-mechanical interface with human skin, (ii) have performance comparable to wet electrodes in recording EEG, EMG and static ECG signals, showing an improvement in the monitoring of ECG signal in dynamic conditions, and (iii) do not need the long-lasting skin preparation as wet electrodes for EEG applications, appearing easy to use and to apply. In conclusion, our microneedles based dry electrodes seem to be a promising alternative to standard wet electrodes for the recording of biosignals in clinical examinations.

Apomorphine is a well-known short-acting dopamine agonist typically used in the treatment of patients with advanced Parkinson's disease. In this work we propose a method for detection of apomorphine in blood plasma through Surface Enhanced Raman Scattering (SERS) technique. Detection can be achieved in a few minutes by simply depositing a drop of the blood plasma containing Apofin ® on silica Thin Layer Chromatography (TLC) substrates and dropping the silver colloid on it. The Raman measurements carried out on the edges of the stain reveal the presence of the drug through its SERS signal which is found to significantly differ from the normal Raman spectrum. We propose a Density Functional Theory (DFT) model for the interpretation of the major SERS signatures of apomorphine in terms of the interaction of the drug molecule with silver.

The present work reports on Raman and Surface Enhanced Raman Scattering (SERS) vibrational fingerprints of β-carotene and haemoglobin in fresh whole blood (i.e. right after blood test) with different laser excitations, i.e. visible (514 nm) and near-infrared (NIR, 785 nm). The use of colloidal silver nanoparticles significantly increases the Raman signal, thus providing a clear SERS spectrum of blood. The collected spectra have been examined and marker bands of β-carotene and of the haem prosthetic group of haemoglobin have been found. In particular, the fundamental features of β-carotene (514 nm excitation), blood proteins and haem molecules (785 nm excitation) were recognized and assigned. Moreover haemoglobin SERS signals can be identified and related with its oxygenation state (oxy-haemoglobin). The data reported show the prospects of Raman and SERS techniques to detect important bio-molecules in a whole blood sample with no pre-treatment.

In this paper, a straightforward method based on elastic light scattering is shown to provide a sensitive and reliable tool for the quantitative determination of receptor-ligand interactions that occur at the surface of suitably designed core-shell nanoparticles. The assay makes use of monodisperse nanocolloids that have minimal optical contrast with the aqueous environment. By properly coating the particles with an appropriate receptor and unreactive amphiphiles, we developed a hybrid system that combines the availability of standard ligands with the necessary bioinvisibility towards the accidental adsorption of nonspecific macromolecules. This system has been used for the study of the interactions between small molecules (Vancomycin-Lipid 2), and between proteins (Avidin-biotinnylated IgG. © 2011 IEEE.

A brain-computer interface (BCI) directly uses brain-activity signals to allow users to operate the environment without any muscular activation. Thanks to this feature, BCI systems can be employed not only as assistive devices, but also as neurorehabilitation tools in clinical settings. However, several critical issues need to be addressed before using BCI in neurorehabilitation, issues ranging from signal acquisition and selection of the proper BCI paradigm to the evaluation of the affective state, cognitive load and system acceptability of the users. Here we discuss these issues, illustrating how a rehabilitation program can benefit from BCI sessions, and summarize the results obtained so far in this field. Also provided are experimental data concerning two important topics related to BCI usability in rehabilitation: the possibility of using dry electrodes for EEG acquisition, and the monitoring of psychophysiological effects during BCI tasks.

An EEG-based brain-computer system can be used to control external devices such as computers, wheelchairs or Virtual Environments. One of the most important applications is a spelling device to aid severely disabled individuals with communication, for example people disabled by amyotrophic lateral sclerosis (ALS). P300-based BCI systems are optimal for spelling characters with high speed and accuracy, as compared to other BCI paradigms such as motor imagery. In this study, 100 subjects tested a P300-based BCI system to spell a 5-character word with only 5 min of training. EEG data were acquired while the subject looked at a 36-character matrix to spell the word WATER. Two different versions of the P300 speller were used: (i) the row/column speller (RC) that flashes an entire column or row of characters and (ii) a single character speller (SC) that flashes each character individually. The subjects were free to decide which version to test. Nineteen subjects opted to test both versions. The BCI system classifier was trained on the data collected for the word WATER. During the real-time phase of the experiment, the subject spelled the word LUCAS, and was provided with the classifier selection accuracy after each of the five letters. Additionally, subjects filled out a questionnaire about age, sex, education, sleep duration, working duration, cigarette consumption, coffee consumption, and level of disturbance that the flashing characters produced. 72.8% (N=81) of the subjects were able to spell with 100% accuracy in the RC paradigm and 55.3% (N=38) of the subjects spelled with 100% accuracy in the SC paradigm. Less than 3% of the subjects did not spell any character correctly. People who slept less than 8h performed significantly better than other subjects. Sex, education, working duration, and cigarette and coffee consumption were not statistically related to differences in accuracy. The disturbance of the flashing characters was rated with a median score of 1 on a scale from 1 to 5 (1, not disturbing; 5, highly disturbing). This study shows that high spelling accuracy can be achieved with the P300 BCI system using approximately 5 min of training data for a large number of non-disabled subjects, and that the RC paradigm is superior to the SC paradigm. 89% of the 81 RC subjects were able to spell with accuracy 80-100%. A similar study using a motor imagery BCI with 99 subjects showed that only 19% of the subjects were able to achieve accuracy of 80-100%. These large differences in accuracy suggest that with limited amounts of training data the P300-based BCI is superior to the motor imagery BCI. Overall, these results are very encouraging and a similar study should be conducted with subjects who have ALS to determine if their accuracy levels are similar.

In order to minimize the impact of systemic toxicity of drugs in the treatment of local acute and chronic inflammatory reactions, the achievement of reliable and efficient delivery of therapeutics in/through the skin is highly recommended. While the use of nanoparticles is now an established practice for drug intravenous targeted delivery, their transdermal penetration is still poorly understood and this important administration route remains almost unexplored. In the present study, we have synthesized magnetic (iron oxide) nanoparticles (MNP) coated with an amphiphilic polymer, developed a water-in-oil emulsion formulation for their topical administration and compared the skin penetration routes with the same nanoparticles deposited as a colloidal suspension. Transmission and scanning electron microscopies provided ultrastructural evidence that the amphiphilic nanoparticles (PMNP) cream formulation allowed the efficient penetration through all the skin layers with a controllable kinetics compared to suspension formulation. In addition to the preferential follicular pathway, also the intracellular and intercellular routes were involved. PMNP that crossed all skin layers were quantified by inductively coupled plasma mass spectrometry. The obtained data suggests that combining PMNP amphiphilic character with cream formulation improves the intradermal penetration of nanoparticles. While PMNP administration in living mice via aqueous suspension resulted in preferential nanoparticle capture by phagocytes and migration to draining lymph nodes, cream formulation favored uptake by all the analyzed dermis cell types, including hematopoietic and non-hematopoietic. Unlike aqueous suspension, cream formulation also favored the maintenance of nanoparticles in the dermal architecture avoiding their dispersion and migration to draining lymph nodes via afferent lymphatics.

Partially or completely paralyzed patients can benefit from advanced neuro-prostheses in which a continuous recording of electroencephalogram (EEG) is required, operating some processing and classification to control a computer (BCI, brain-computer interfaces). Patients are so allowed to control external devices or to communicate simple messages through the computer, just concentrating their attention on codified movements or on a letter or icon on a digital keyboard. Conventional electrodes usually require skin preparation and application of electrolytic gel for high quality low amplitude biopotentials recordings and are not suitable for being easily used by patient or caregivers at home in BCI or equivalent systems. In this report we describe the fabrication and characterization of dry (gel not required), non-invasive, user-friendly biopotential electrodes. The electrodes consist of a bidimensional array of micro-needles designed to pierce the first dielectric skin layer (stratum corneum) and establishing a direct contact with the living and electrical conducting cells in the epidermis (no blood vessels and nerve terminations). The easy and immediate application of the spiked electrodes makes them also attractive for every surface long-term biosignal measurements, even at patient's home (EEG, electrocardiogram, etc).

Since the development of methods of electronic communication, clinicians have been using information and communication technologies for the exchange of health-related information. However, the evolution and increased availability of new shared media, such as the internet and virtual reality, are changing the ways in which patients and clinicians relate and communicate. To date, some e-health applications have improved the quality of healthcare, and later they will lead to substantial cost savings. For instance, physicians can review radiological films and pathology slides in remote sites, or assist and perform surgery via remote robotics. However, most of these applications are used for discrete clinical activities, such as scripting, lab-testing, patient monitoring, and condition-specific diagnostics and treatment. The next challenge is their integration within a common clinical framework able to radically change our experience of healthcare. Ambient Intelligence (AmI), a new paradigm in information technology, in which people are empowered through a digital environment that is aware of their presence and context, and is sensitive, adaptive, and responsive to their needs, habits, gestures and emotions, is the next logical step of this process. In this sense, the AmI paradigm can be seen as the direct extension of today's concept of ubiquitous computing: the integration of microprocessors into everyday objects. How does the emergence of the AmI paradigm influence the future of healthcare? Using a scenario-based approach the chapter will outline the possible role of AmI in healthcare by focusing on both its technological and relational nature. In this sense, clinicians and healthcare providers that want to successfully exploit the potential of AmI need to give significant attention to technology, ergonomics, project management, human factors and organisational changes in the structure of the relevant health service.