Pragmatic language disorder in Parkinson's disease and the potential effect of cognitive reserve

It is known that patients with Parkinson\u2019s Disease (PD) may show deficits in several areas of cognition, including speech and language abilities. One domain of particular interest is pragmatics, which refers to the capacity of using language in context for a successful communication. Several studies showed that some specific aspects of pragmatics \u2013 both in production and in comprehension \u2013 might be impaired in patients with PD. However, a clear picture of pragmatic abilities in PD is still missing, as most of the existing studies focused on specific aspects of the pragmatic competence rather than on sketching a complete pragmatic profile. Moreover, little is known on the potential role of protective factors in compensating the decline of communicative skills as the disease progresses. The present study has two aims: (1) to provide a complete picture of pragmatic abilities in patients with PD, by using a comprehensive battery (Assessment of Pragmatic Abilities and Cognitive Substrates, APACS) and by investigating the relationship with other aspects of cognitive functioning (e.g., working memory and Theory of Mind) and (2) to investigate whether Cognitive Reserve, i.e., the resilience to cognitive impairment provided by life experiences and activities, may compensate for the progressive pragmatic deficits in PD. We found that patients with PD, compared to healthy matched controls, had worse performance in discourse production and in the description of scenes, and that these impairments were tightly correlated with the severity of motor impairment, suggesting reduced intentionality of engaging in a communicative exchange. Patients with PD showed also an impairment in comprehending texts and humor, suggesting a problem in inferring from stories, which was related to general cognitive impairment. Notably, we did not find any significant difference between patients and controls in figurative language comprehension, a domain that is commonly impaired in other neurodegenerative diseases. This might be indicative of a specific profile of pragmatic impairment in patients with PD, worth of further investigation. Finally, Cognitive Reserve measures showed a high degree of association with pragmatic comprehension abilities, suggesting that the modification of life-styles could be a good candidate for compensating the possible problems in understanding the pragmatic aspects of language experienced by patients with PD

DESIGN, SYNTHESIS AND CHARACTERIZATION OF MAGNETIC BIO-INORGANIC NANOSYSTEMS WITH THERANOSTIC FEATURES.

The aim of my PhD project is to obtain immune nanosystems having, at the same time, diagnostic and therapeutic functions. To combine these applications, our nanosystems will be constituted by magnetic nanoparticles linked to an antibody fragment. Magnetic nanoparticles , (I will synthesize cubic ferrites mainly of iron, but also of other transition metals such as cobalt), give us both diagnostic properties, because they are already used as contrast agents in magnetic resonance imaging (MRI), and therapeutic properties, because they could be used in hypertemia experiments for cancer treatment. Furthermore they allow us to monitor the response to therapy. Instead the functionalization of magnetic nanoparticles with a specific antibody fragment (in particular we will start with the fragment of Trastuzumab, a monoclonal antibody that binds to human epidermal growth factor receptor 2 (HER2) )first provides us an active targeting. Indeed HER2 receptor is overexpressed in 20-30% of breast cancers and also in some types of adenocarcinoma of the stomach or gastro-oesophageal junction. Then Trastuzumab give us other therapeutic properties because, with different mechanisms of action, modifies cellular proliferation. So we want to overcame the limitation of traditional chemotherapy, improving the treatment specificity and dramatically reducing toxicity and unspecific side effects. We will start to synthesize magnetic nanoparticles by solvothermal methods, that is , a high-temperature decomposition of metal precursors in non-coordinating solvents and in the presence of surfactants . But in order to obtain nanoparticles water soluble, native surfactants like oleic acid will be exchanged with suitable linker. Particular attention will be given to the synthesis of the latter. Hydrophilic linker will be formed by: a catechol moiety to anchor surfactant to magnetic nanoparticles, a maleimide group able to reacting with free thiol group present on the Trastuzumab antibody fragment and a long polyethylene glycol chain (with molecular weight around 5000 KDa) to enhance water solubility and stability. PEG chain also provides magnetic nanoparticles of a \u201cstealth effect\u201d .They are less recognised by circulating plasma proteins opsonins which adsorb onto their surface and then are removed from the blood by the circulating monocytes and fixed macrophages. So the plasma half-life of these nanoparticles is increased together with the probability of arriving to desided target. We have to characterize these immuno-nanosystems under different aspects. The magnetic NPs will be analyzed:- by transmission electron microscopy (TEM) to study shape, dimensions and chemical composition; - by SQUID (Superconducting Quantum Interference Devices )magnetometry, to measure the magnetical properties - by measurements of proton relaxivity and specific absortion rate (SAR) to quantify capacity of NPs to be used as contrast agents and mediators for hyperthermia We will also study water stability of immune nanoparticles in function of time, pH and temperature with DLS analysis. Afterwards we will investigate in vitro toxicity of immune-nanosystems after their uptake from cells overexpressing HER2 receptor

Violent and Complex Behaviors and Non-Restorative Sleep Are the Main Features of Disorders of Arousal in Adulthood: Real Picture or a More Severe Phenotype?

Disorders of arousal (DoA) are NREM parasomnias characterized by motor and emotional behaviors emerging from incomplete arousals from deep sleep. DoA are largely present in pediatric populations, a period during which they are labeled as self-limited manifestations. However, an extensive literature has shown that DoA can persist in adulthood, with different characteristics from childhood DoA. Adult DoA patients usually report excessive daily sleepiness, sleep-related violence during DoA episodes or potentially harmful behaviors, which are rare in childhood. The semeiological features of DoA episodes in adulthood may complicate differential diagnoses with other motor manifestations during sleep, in particular sleep-related hypermotor epilepsy. However, it cannot be excluded that adults with DoA attending sleep centers constitute a more severe phenotype, thus not being representative of adult DoA in the general population. Video-polysomnographic studies of DoA document a spectrum of motor patterns of different complexities, the simplest of which may often go unnoticed. Despite the different complexities of the episodes, neurophysiologic studies showed the co-existence of deep sleep and wakefulness during DoA episodes or even before their onset. These aspects make DoA an ideal model to investigate the mechanisms regulating local sleep, sleep arousal and cognitive functions including spatial and temporal orientation, attention or memory

4D Printing of Humidity-Driven Seed Inspired Soft Robots

Geraniaceae seeds represent a role model in soft robotics thanks to their ability to move autonomously across and into the soil driven by humidity changes. The secret behind their mobility and adaptivity is embodied in the hierarchical structures and anatomical features of the biological hygroscopic tissues, geometrically designed to be selectively responsive to environmental humidity. Following a bioinspired approach, the internal structure and biomechanics of Pelargonium appendiculatum (L.f.) Willd seeds are investigated to develop a model for the design of a soft robot. The authors exploit the re-shaping ability of 4D printed materials to fabricate a seed-like soft robot, according to the natural specifications and model, and using biodegradable and hygroscopic polymers. The robot mimics the movement and performances of the natural seed, reaching a torque value of ≈30 µN m, an extensional force of ≈2.5 mN and it is capable to lift ≈100 times its own weight. Driven by environmental humidity changes, the artificial seed is able to explore a sample soil, adapting its morphology to interact with soil roughness and cracks

Continuous 2D trajectory decoding from attempted movement: across-session performance in able-bodied and feasibility in a spinal cord injured participant

Objective. In people with a cervical spinal cord injury (SCI) or degenerative diseases leading to limited motor function, restoration of upper limb movement has been a goal of the brain-computer interface field for decades. Recently, research from our group investigated non-invasive and real-time decoding of continuous movement in able-bodied participants from low-frequency brain signals during a target-tracking task. To advance our setup towards motor-impaired end users, we consequently chose a new paradigm based on attempted movement. Approach. Here, we present the results of two studies. During the first study, data of ten able-bodied participants completing a target-tracking/shape-tracing task on-screen were investigated in terms of improvements in decoding performance due to user training. In a second study, a spinal cord injured participant underwent the same tasks. To investigate the merit of employing attempted movement in end users with SCI, data of the spinal cord injured participant were recorded twice; once within an observation-only condition, and once while simultaneously attempting movement. Main results. We observed mean correlations well above chance level for continuous motor decoding based on attempted movement in able-bodied participants. Additionally, no global improvement over three sessions within five days, both in sensor and in source space, could be observed across all participants and movement parameters. In the participant with SCI, decoding performance well above chance was found. Significance. No presence of a learning effect in continuous attempted movement decoding in able-bodied participants could be observed. In contrast, non-significantly varying decoding patterns may promote the use of source space decoding in terms of generalized decoders utilizing transfer learning. Furthermore, above-chance correlations for attempted movement decoding ranging between those of observation only and executed movement were seen in one spinal cord injured participant, suggesting attempted movement decoding as a possible link between feasibility studies in able-bodied and actual applications in motor impaired end users

Enhanced in vitro magnetic cell targeting of doxorubicin-loaded magnetic liposomes for localized cancer therapy

: The lack of efficient targeting strategies poses significant limitations on the effectiveness of chemotherapeutic treatments. This issue also affects drug-loaded nanocarriers, reducing nanoparticles cancer cell uptake. We report on the fabrication and in vitro characterization of doxorubicin-loaded magnetic liposomes for localized treatment of liver malignancies. Colloidal stability, superparamagnetic behavior and efficient drug loading of our formulation were demonstrated. The application of an external magnetic field guaranteed enhanced nanocarriers cell uptake under cell medium flow in correspondence of a specific area, as we reported through in vitro investigation. A numerical model was used to validate experimental data of magnetic targeting, proving the possibility of accurately describing the targeting strategy and predict liposomes accumulation under different environmental conditions. Finally, in vitro studies on HepG2 cancer cells confirmed the cytotoxicity of drug-loaded magnetic liposomes, with cell viability reduction of about 50% and 80% after 24 h and 72 h of incubation, respectively. Conversely, plain nanocarriers showed no anti-proliferative effects, confirming the formulation safety. Overall, these results demonstrated significant targeting efficiency and anticancer activity of our nanocarriers and superparamagnetic nanoparticles entrapment could envision the theranostic potential of the formulation. The proposed magnetic targeting study could represent a valid tool for pre-clinical investigation regarding the effectiveness of magnetic drug targeting

Toward the use of temporary tattoo electrodes for impedancemetric respiration monitoring and other electrophysiological recordings on skin

The development of dry, ultra-conformable and unperceivable temporary tattoo electrodes (TTEs), based on the ink-jet printing of poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) on top of commercially available temporary tattoo paper, has gained increasing attention as a new and promising technology for electrophysiological recordings on skin. In this work, we present a TTEs epidermal sensor for real time monitoring of respiration through transthoracic impedance measurements, exploiting a new design, based on the application of soft screen printed Ag ink and magnetic interlink, that guarantees a repositionable, long-term stable and robust interconnection of TTEs with external “docking” devices. The efficiency of the TTE and the proposed interconnection strategy under stretching (up to 10%) and over time (up to 96 h) has been verified on a dedicated experimental setup and on humans, fulfilling the proposed specific application of transthoracic impedance measurements. The proposed approach makes this technology suitable for large-scale production and suitable not only for the specific use case presented, but also for real time monitoring of different bio-electric signals, as demonstrated through specific proof of concept demonstrators