Iron deposition and inflammation in multiple sclerosis. Which one comes first?

Whether iron deposition is an epiphenomenon of the multiple sclerosis (MS) disease process or may play a primary role in triggering inflammation and disease development remains unclear at this time, and should be studied at the early stages of disease pathogenesis. However, it is difficult to study the relationship between iron deposition and inflammation in early MS due to the delay between the onset of symptoms and diagnosis, and the poor availability of tissue specimens. In a recent article published in BMC Neuroscience, Williams et al. investigated the relationship between inflammation and iron deposition using an original animal model labeled as "cerebral experimental autoimmune encephalomyelitis", which develops CNS perivascular iron deposits. However, the relative contribution of iron deposition vs. inflammation in the pathogenesis and progression of MS remains unknown. Further studies should establish the association between inflammation, reduced blood flow, iron deposition, microglia activation and neurodegeneration. Creating a representative animal model that can study independently such relationship will be the key factor in this endeavor

Principal components analysis based control of a multi-dof underactuated prosthetic hand

<p>Abstract</p> <p>Background</p> <p>Functionality, controllability and cosmetics are the key issues to be addressed in order to accomplish a successful functional substitution of the human hand by means of a prosthesis. Not only the prosthesis should duplicate the human hand in shape, functionality, sensorization, perception and sense of body-belonging, but it should also be controlled as the natural one, in the most intuitive and undemanding way. At present, prosthetic hands are controlled by means of non-invasive interfaces based on electromyography (EMG). Driving a multi degrees of freedom (DoF) hand for achieving hand dexterity implies to selectively modulate many different EMG signals in order to make each joint move independently, and this could require significant cognitive effort to the user.</p> <p>Methods</p> <p>A Principal Components Analysis (PCA) based algorithm is used to drive a 16 DoFs underactuated prosthetic hand prototype (called CyberHand) with a two dimensional control input, in order to perform the three prehensile forms mostly used in Activities of Daily Living (ADLs). Such Principal Components set has been derived directly from the artificial hand by collecting its sensory data while performing 50 different grasps, and subsequently used for control.</p> <p>Results</p> <p>Trials have shown that two independent input signals can be successfully used to control the posture of a real robotic hand and that correct grasps (in terms of involved fingers, stability and posture) may be achieved.</p> <p>Conclusions</p> <p>This work demonstrates the effectiveness of a bio-inspired system successfully conjugating the advantages of an underactuated, anthropomorphic hand with a PCA-based control strategy, and opens up promising possibilities for the development of an intuitively controllable hand prosthesis.</p

Custom CGH array profiling of copy number variations (CNVs) on chromosome 6p21.32 (HLA locus) in patients with venous malformations associated with multiple sclerosis

<p>Abstract</p> <p>Background</p> <p>Multiple sclerosis (MS) is a complex disorder thought to result from an interaction between environmental and genetic predisposing factors which have not yet been characterised, although it is known to be associated with the HLA region on 6p21.32. Recently, a picture of chronic cerebrospinal venous insufficiency (CCSVI), consequent to stenosing venous malformation of the main extra-cranial outflow routes (VM), has been described in patients affected with MS, introducing an additional phenotype with possible pathogenic significance.</p> <p>Methods</p> <p>In order to explore the presence of copy number variations (CNVs) within the HLA locus, a custom CGH array was designed to cover 7 Mb of the HLA locus region (6,899,999 bp; chr6:29,900,001-36,800,000). Genomic DNA of the 15 patients with CCSVI/VM and MS was hybridised in duplicate.</p> <p>Results</p> <p>In total, 322 CNVs, of which 225 were extragenic and 97 intragenic, were identified in 15 patients. 234 known polymorphic CNVs were detected, the majority of these being situated in non-coding or extragenic regions. The overall number of CNVs (both extra- and intragenic) showed a robust and significant correlation with the number of stenosing VMs (Spearman: r = 0.6590, p = 0.0104; linear regression analysis r = 0.6577, p = 0.0106).</p> <p>The region we analysed contains 211 known genes. By using pathway analysis focused on angiogenesis and venous development, MS, and immunity, we tentatively highlight several genes as possible susceptibility factor candidates involved in this peculiar phenotype.</p> <p>Conclusions</p> <p>The CNVs contained in the HLA locus region in patients with the novel phenotype of CCSVI/VM and MS were mapped in detail, demonstrating a significant correlation between the number of known CNVs found in the HLA region and the number of CCSVI-VMs identified in patients. Pathway analysis revealed common routes of interaction of several of the genes involved in angiogenesis and immunity contained within this region. Despite the small sample size in this pilot study, it does suggest that the number of multiple polymorphic CNVs in the HLA locus deserves further study, owing to their possible involvement in susceptibility to this novel MS/VM plus phenotype, and perhaps even other types of the disease.</p

Cognitive vision system for control of dexterous prosthetic hands: Experimental evaluation

<p>Abstract</p> <p>Background</p> <p>Dexterous prosthetic hands that were developed recently, such as SmartHand and i-LIMB, are highly sophisticated; they have individually controllable fingers and the thumb that is able to abduct/adduct. This flexibility allows implementation of many different grasping strategies, but also requires new control algorithms that can exploit the many degrees of freedom available. The current study presents and tests the operation of a new control method for dexterous prosthetic hands.</p> <p>Methods</p> <p>The central component of the proposed method is an autonomous controller comprising a vision system with rule-based reasoning mounted on a dexterous hand (CyberHand). The controller, termed cognitive vision system (CVS), mimics biological control and generates commands for prehension. The CVS was integrated into a hierarchical control structure: 1) the user triggers the system and controls the orientation of the hand; 2) a high-level controller automatically selects the grasp type and size; and 3) an embedded hand controller implements the selected grasp using closed-loop position/force control. The operation of the control system was tested in 13 healthy subjects who used Cyberhand, attached to the forearm, to grasp and transport 18 objects placed at two different distances.</p> <p>Results</p> <p>The system correctly estimated grasp type and size (nine commands in total) in about 84% of the trials. In an additional 6% of the trials, the grasp type and/or size were different from the optimal ones, but they were still good enough for the grasp to be successful. If the control task was simplified by decreasing the number of possible commands, the classification accuracy increased (e.g., 93% for guessing the grasp type only).</p> <p>Conclusions</p> <p>The original outcome of this research is a novel controller empowered by vision and reasoning and capable of high-level analysis (i.e., determining object properties) and autonomous decision making (i.e., selecting the grasp type and size). The automatic control eases the burden from the user and, as a result, the user can concentrate on what he/she does, not on how he/she should do it. The tests showed that the performance of the controller was satisfactory and that the users were able to operate the system with minimal prior training.</p

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference

Comparative epidemiology of multiple sclerosis and dental caries.

The geographical distribution and other epidemiological characteristics of multiple sclerosis (MS) are compared with those of dental caries. The rates of death due to MS in Australian states are linearly related to the numbers of decayed, missing, and filled (DMF) teeth found in individuals from those states (r=0.97, P less than 0.002). In the United States of America, a strong positive correlation (r=0.55, P less than 0.001) also exists between MS death rates and dental caries indices. The prevalence of MS in 45 countries or areas correlates well with the frequencies of DMF teeth among children of school age in those locations (r=0.78, P less than 0.001). The prevalence of MS also correlates well with the percentage of edentulous individuals in certain countries (r=0.99, P less than 0.001). A review of the literature shows that the risk for dental caries is lower among the following groups: the lower socioeconomic classes in the United States of America; Chinese immigrants to England compared with natives; blacks compared with whites; and males compared with females. The dental caries risk is higher during pregnancy and lactation. All these trends have been described for MS as well. It is suggested that dental caries may be a more accurate epidemiological model for MS than poliomyelitis. It is also suggested that MS and dental caries may share certain aetiological factors, two of which may be dietary excess of certain fats, and vitamin D deficiency