Persico A.M.,Biomedical University of Rome |
Napolioni V.,Biomedical University of Rome
Behavioural Brain Research | Year: 2013
Autism spectrum disorder (ASD) is a severe neuropsychiatric disease with strong genetic underpinnings. However, genetic contributions to autism are extremely heterogeneous, with many different loci underlying the disease to a different extent in different individuals. Moreover, the phenotypic expression (. i.e., "penetrance") of these genetic components is also highly variable, ranging from fully penetrant point mutations to polygenic forms with multiple gene-gene and gene-environment interactions. Furthermore, many genes involved in ASD are also involved in intellectual disability, further underscoring their lack of specificity in phenotypic expression. We shall hereby review current knowledge on the genetic basis of ASD, spanning genetic/genomic syndromes associated with autism, monogenic forms due to copy number variants (CNVs) or rare point mutations, mitochondrial forms, and polygenic autisms. Finally, the recent contributions of genome-wide association and whole exome sequencing studies will be highlighted. © 2013.
Gaudio S.,Biomedical University of Rome |
Quattrocchi C.C.,Biomedical University of Rome
Neuroscience and Biobehavioral Reviews | Year: 2012
Body image distortion is a key symptom of anorexia nervosa (AN). The majority of the neuroimaging studies on body image distortion in AN conceptualized it as an unidimensional symptom. However, behavioural research considers such symptom as a multidimensional construct. Our paper systematically reviews the functional magnetic resonance (fMRI) studies on body image distortion in AN and classifies them according to a speculative model of body image distortion, that consists of the three most widely accepted components in the behavioural research: perceptive, affective and cognitive. We found that: (1) the perceptive component is mainly related to alterations of the precuneus and the inferior parietal lobe; (2) the affective component is mainly related to alterations of the prefrontal cortex, the insula and the amygdala; (3) the cognitive component has been weakly explored. These evidences seem to confirm that specific neural alterations are related to the components of the body image distortion in AN. Further neuroimaging studies are needed to better understand the complexity of the body image distortion in AN. © 2012 Elsevier Ltd.
D'Amelio M.,Irccs S Lucia Foundation |
D'Amelio M.,Biomedical University of Rome |
Rossini P.M.,Catholic University
Progress in Neurobiology | Year: 2012
The human brain contains about 100 billion neurons forming an intricate network of innumerable connections, which continuously adapt and rewire themselves following inputs from external and internal environments as well as the physiological synaptic, dendritic and axonal sculpture during brain maturation and throughout the life span.Growing evidence supports the idea that Alzheimer's disease (AD) targets selected and functionally connected neuronal networks and, specifically, their synaptic terminals, affecting brain connectivity well before producing neuronal loss and compartmental atrophy.The understanding of the molecular mechanisms underlying the dismantling of neuronal circuits and the implementation of 'clinically oriented' methods to map-out the dynamic interactions amongst neuronal assemblies will enhance early/pre-symptomatic diagnosis and monitoring of disease progression. More important, this will open the avenues to innovative treatments, bridging the gap between molecular mechanisms and the variety of symptoms forming disease phenotype.In the present review a set of evidence supports the idea that altered brain connectivity, exhausted neural plasticity and aberrant neuronal activity are facets of the same coin linked to age-related neurodegenerative dementia of Alzheimer type.Investigating their respective roles in AD pathophysiology will help in translating findings from basic research to clinical applications. © 2012 Elsevier Ltd.
Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: SEC-2011.2.2-2 | Award Amount: 4.80M | Year: 2012
Security and quality of life in industrialized countries depend on continuous and coordinate performance of a set of infrastructures (energy systems, ICT systems, transportation etc) which can be therefore defined critical infrastructures (CI). STRUCTURES - Strategies for The impRovement of critical infrastrUCTUre Resilience to Electromagnetic attackS aims at analyzing possible effects of electromagnetic (e.m.) attacks, and in particular of intentional e.m. interference (IEMI), on such CIs, at assessing their impact for our defense and economic security, at identifying innovative awareness and protection strategies and at providing a picture for the policy makers on the possible consequences of an electromagnetic attack. The work is organized into four main tasks, namely: - Scenario assessment (IEMI threat analysis; CIs analysis; modelling and experimental methodologies for investigation) - Investigation (assessment of susceptibility levels of critical systems/units; analysis and testing; innovative protection strategy identification) - IEMI sensors for real-time awareness of threats and implementation of active protection strategies - Delivery of pre-regulatory guidelines to support people in the understanding of IEMI related risk and in planning/application of proper protection strategies. Existing standards such as the Business Continuity Management approach (BS25999 standard) and other standardized CIIP (Critical Information Infrastructures Protection) polices will be considered in order to properly identify critical items and to set criteria for risk acceptance. Already existing results relevant to EMC (ElectroMagnetic Compatibility), LEMP/NEMP/HEMP (Lightning/Nuclear/High altitude ElectroMagnetic Pulse) will be considered as possible starting points leading to find effective solution to IEMI problem. Topological approach, Risk Analysis and 3D modelling tools will be mainly applied for the analysis to a comprehensive set of reference configurations. P
Agency: European Commission | Branch: FP7 | Program: NoE | Phase: SEC-2012.7.4-2 | Award Amount: 7.66M | Year: 2013
The Critical Infrastructure Preparedness and Resilience Research Network or CIPRNet establishes a Network of Excellence in Critical Infrastructure Protection (CIP) R&D for a wide range of stakeholders including (multi)national emergency management, critical infrastructure (CI) operators, policy makers, and the society. CIPRNet builds a long-lasting, durable virtual centre of shared and integrated knowledge and expertise in CIP and CI MS&A (Modelling, Simulation and Analysis) by integrating part of the resources of the CIPRNet partners and their R&D activities acquired in more than 50 EU co-funded projects. This centre will form the foundation for the European Infrastructures Simulation & Analysis Centre (EISAC) by 2020. CIPRNet will strengthen and structure the European Research Area on CIP by using its network to outreach and link isolated research kernels and adjacent R&D areas. Activities include training and the ask the CIPRNet expert service to find and access the right pockets of CIP expertise in Europe. Moreover, CIPRNet enhances the resilience of CI in Europe by improving the knowledge and understanding, preparation and mitigation of CI disruptions and their consequences. The CIPRNet Joint Programme of Activities (JPA) integrates and makes complementary use of CIP and related knowledge, expertise, and resources (e.g., tools, methods, top experts and other staff) of the partners. The JPA forms the stepping stone for the development of the long-lasting cooperation and integration of R&D activities of the partners. The European CIP innovation process is boosted as substantial resources are integrated and focussed on the creation of added-value decision-support capabilities for (multi)national emergency management and CI owners. These capabilities provide timely, actionable, risk-informed CIP analyses and strategies that support the preparation for, response to, and recovery from major CI disruptions. The interest in CIPRNet is shown by 24 letters of support.
Zobel B.B.,Biomedical University of Rome
Spine | Year: 2012
Cross-sectional study using T1ρ magnetic resonance imaging (MRI) of lumbar spine in healthy young adults. To evaluate early intervertebral disc degeneration (IDD) quantified by T1ρ- and T2-weighted MRI in asymptomatic young adults and to correlate T1ρ value with Pfirrmann degenerative grade, sex, and body mass index (BMI). Intervertebral disc starts early to degenerate losing proteoglycan content in the nucleus pulposus (NP). A potential tool for the study of early stage of IDD is T1ρ MRI. T1ρ relaxation time of human discs has been correlated to proteoglycan content in previous studies. T1ρ- and T2-weighted images of the lumbar spine were obtained for 63 asymptomatic young subjects (34 men and 29 women; mean age, 22.95 ± 1.8 yr), with a 1.5-T MRI scanner. T1ρ mapping and values in the NP and anulus fibrosus (n = 315) were obtained. Degenerative grade was assessed using T2-weighted images, according to the Pfirrmann scale. Differences in T1ρ value between sexes, BMI, and linear regression analyses with degenerative grade were determined. T1ρ values of NPs were significantly higher than those of anulus fibrosus at all levels. T1ρ values were significantly lower in women at L3-L4 and L4-L5 discs (P < 0.05). T1ρ values decreased linearly with degenerative grade. However, nondegenerated discs (Pfirrmann grades 1 and 2) showed a wide range of T1ρ relaxation time. No significant correlation was observed between T1ρ value and BMI. The data of this study showed a significant difference in IDD onset between sexes. T1ρ values correlate with Pfirrmann degenerative grade in young adults. However, the wide distribution of T1ρ values in healthy intervertebral disc highlights the low sensitivity of Pfirrmann grade to detect the early IDD changes. T1ρ can be potentially used as a clinical tool to identify early IDD and to create a reliable quantitative scale.
Minotti G.,Biomedical University of Rome
Journal of Pharmacology and Experimental Therapeutics | Year: 2013
Antitumor drugs may cause asymptomatic diastolic dysfunction that introduces a lifetime risk of heart failure or myocardial infarction. Cardio-oncology is the discipline committed to the cardiac surveillance and management of cancer patients and survivors; however, cardio-oncology teams do not always attempt to treat early diastolic dysfunction. Common cardiovascular drugs, such as b blockers or angiotensin-converting enzyme inhibitors or others, would be of uncertain efficacy in diastolic dysfunction. This perspective describes the potential value of ranolazine, an antianginal drug that improves myocardial perfusion by relieving diastolic wall tension and dysfunction. Ranolazine acts by inhibiting the late inward sodium current, and pharmacological reasonings anticipate that antitumor anthracyclines and nonanthracycline chemotherapeutics might well induce anomalous activation of this current. These notions formed the rationale for a clinical study of the efficacy and safety of ranolazine in cancer patients. This study was not designed to demonstrate that ranolazine reduced the lifetime risk of cardiac events; it was designed as a short term proof-of-concept study that probed the following hypotheses: 1) asymptomatic diastolic dysfunction could be detected a few days after patients completed antitumor therapy, and 2) ranolazine was active and safe in relieving echocardiographic and/or biohumoral indices of diastolic dysfunction, measured at 5 weeks or 6 months of ranolazine administration. These facts illustrate the translational value of pharmacology, which goes from identifying therapeutic opportunities to validating hypotheses in clinical settings. Pharmacology is a key to the success of cardio-oncology. Copyright © 2013 by The American Society for Pharmacology and Experimental Therapeutics.
Agency: European Commission | Branch: H2020 | Program: RIA | Phase: ICT-22-2014 | Award Amount: 3.41M | Year: 2015
Around 80 million people in the EU, a sixth of its population, have a disability. Beside this, accessibility is a basic right for all persons with disabilities according to the article 9 of the United Nations Convention on the Rights of Persons with Disabilities signed by the European Commission in 2010. The purpose of accessibility is to enable persons with disabilities to live independently and to participate in all aspects of life. The AIDE project has the ambition to develop and pre-clinical validate a novel and revolutionary modular and adaptive multimodal human-machine interface to allow that moderately and severely impaired people interact with intelligent devices to perform daily activities and to fully participate in society. It will, furthermore, focus on the development of a totally new shared-control paradigm for assistive devices that integrates information from identification of residual abilities, behaviours, emotional state and intentions of the user on one hand and analysis of the environment and context factors on the other hand. A series of applications for the AIDE system have been identified across several domains in which disabled people could greatly benefit: communication, home automation, wearable robots for assisting in activities of daily living and entertainment. The validation of AIDE system will be deployed during 8 months to 5-10 users in the UK at Cedar Foundation. The final goal of this process will be to provide the proof of concept of the advantages of the AIDE system based on a novel modular, natural and adaptive multimodal interface and a shared control system to assist disabled people in accordance with specific user needs.
Agency: European Commission | Branch: H2020 | Program: ERC-STG | Phase: ERC-StG-2015 | Award Amount: 1.49M | Year: 2016
Amputation distorts the body representation, a fundamental aspect of self-consciousness. Hand prostheses counteract sensorimotor impairment, but poor attention has been posed to target the alteration of body-image. RESHAPE aims to study prosthesis embodiment, identify what makes a hand prosthesis easily embodiable, and test non-invasive brain stimulation to facilitate the embodiment. Amputees claim to perceive prostheses as tools; RESHAPE enables amputees to project their self into the prosthesis, improving in parallel their dexterity. The first of three phases develops the enabling technology and defines the embodiment protocol. The following phase evaluates thirty myoelectric-prosthesis users and the first of two amputees implanted with peripheral neural electrodes, for functional ability, prosthesis embodiment and acceptability and for phantom limb pain (PLP), before and after neuromodulation. In the last phase, a neuro-controlled prosthesis is optimized in line with the specifications defined in the previous phase and tested in the second implanted amputee. An embodiment and a sensory/manipulation platform, integrating a discrimination setup with sensorized wearable systems, induce and weigh the embodiment and its impact on prosthesis performance. Embodiment neural correlates are investigated with EEG and fMRI-based techniques, thanks to a prosthesis virtual model controllable inside the scanner. Patients are stimulated with a homeostatic plasticity-based rTMS either on premotor cortex or on intraparietal sulcus. A robot-aided TMS compensates head-coil relative displacement, allowing the subject to operate the prosthesis during the stimulation. RESHAPE is a paradigm shift in Prosthetics. It offers the guidelines for highly-embodiable prostheses, four technological platforms beyond the state-of-the-art, novel insights on how tools shape the body-image, the proof of a TMS-induced embodiment and a new strategy to readdress amputees aberrant plasticity and PLP.
Agency: European Commission | Branch: H2020 | Program: RIA | Phase: SC1-PM-11-2016-2017 | Award Amount: 5.56M | Year: 2017
The World Health Organisation (WHO) has included low back pain in its list of twelve priority diseases. Notably, Degenerative disc disease (DDD) presents a large, unmet medical need which results in a disabling loss of mechanical function. Today, no efficient therapy is available. Chronic cases often receive surgery, which may lead to biomechanical problems and accelerated degeneration of adjacent segments. Our consortium partners have developed and studied stem cell-based, regenerative therapies with encouraging results in phase 1 and 2a trials. Patients exhibited rapid and progressive improvement of functional and pain indexes by 50% within 6 months and by 65% to 78% after 1 year with no side effects. In addition, MRI T2 relaxation measurements demonstrated a significant improvement. To develop the worlds first rigorously proven, effective treatment of DDD, RESPINE aims to assess, via a multicentre, randomized, controlled, phase 2b clinical trial including 112 patients with DDD, the efficacy of an allogenic intervertebral mesenchymal stem cell (MSC)-based therapy. This innovative therapy aims to rapidly (within 3 months) and sustainably (at least 24 months) reduce pain and disability. In addition, the consortium aims to provide new knowledge on immune response & safety associated with allogeneic BM-MSC intradiscal injection. This simple procedure would be cost-effective, minimally invasive, and standardised. The transfer to the clinic will be prepared at a cost below 10k thanks to the strategy of production of allogenic cells, automation & EU standardisation. At the end of the RESPINE trial, we aim to propose a broadly available and clinically applicable treatment for DDD, marketed by European SMEs.