Parkinsonian Rigidity Depends on the Velocity of Passive Joint Movement

Background. It has been long believed that Parkinsonian rigidity is not velocity-dependent based on the neurological examination. However, this has not been verified scientifically. Methods. The elbow joints of 20 Parkinson’s disease patients were passively flexed and extended, and two characteristic values, the elastic coefficient (elasticity) and the difference in bias (difference in torque measurements for extension and flexion), were identified from a plot of the angle and torque characteristics. Flexion and extension were done at two different velocities, 60°/s and 120°/s, and a statistical analysis was performed to determine whether the changes in these characteristic values were velocity-dependent. Results. The elastic coefficient was not velocity-dependent, but the difference in bias increased in a velocity-dependent manner (P=0.0017). Conclusions. The features of rigidity may differ from the conventional definition, which states that they are not dependent on the velocity of joint movement

Evaluation and Training of Human Finger Tapping Movements

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A CPG synergy model for evaluation of human finger tapping movements

Abstract—This paper proposes the CPG synergy model – a biomimetic rhythm generator model based on central pattern generators (CPGs) and muscle synergy theory to enable evaluation of rhythmic motions with non-stationary characteristics such as human finger tapping movements. The model consists of multiple CPGs to approximate the complex rhythmic movement of humans, and has the potential to allow evaluation of abnormal movements in patients with motor function impairments such as Parkinson’s disease (PD). To verify the validity of the proposed model, comparison experiments were conducted using model parameters (i.e., syn-ergies, weight coefficients and time-shift parameters) extracted from finger tapping movements performed by individuals in a healthy subject group and a PD patient group. The results showed that the number of synergies, the second moment of synergy shapes and the coefficient of variation of maximum weight coefficients show significant differences for each subject group, and indicated that the model could be used to evaluate irregular rhythmic movements as well as regular ones. I

Postural instability via a loss of intermittent control in elderly and patients with Parkinson's disease: a model-based and data-driven approach

Postural instability is one of the major symptoms of Parkinson's disease. Here, we assimilated a model of intermittent delay feedback control during quiet standing into postural sway data from healthy young and elderly individuals as well as patients with Parkinson's disease to elucidate the possible mechanisms of instability. Specifically, we estimated the joint probability distribution of a set of parameters in the model using the Bayesian parameter inference such that the model with the inferred parameters can best-fit sway data for each individual. It was expected that the parameter values for three populations would distribute differently in the parameter space depending on their balance capability. Because the intermittent control model is parameterized by a parameter associated with the degree of intermittency in the control, it can represent not only the intermittent model but also the traditional continuous control model with no intermittency. We showed that the inferred parameter values for the three groups of individuals are classified into two major groups in the parameter space: one represents the intermittent control mostly for healthy people and patients with mild postural symptoms and the other the continuous control mostly for some elderly and patients with severe postural symptoms. The results of this study may be interpreted by postulating that increased postural instability in most Parkinson's patients and some elderly persons might be characterized as a dynamical disease

Measurement and Evaluation of Finger Tapping Movements Using Log-linearized Gaussian Mixture Networks

This paper proposes a method to quantitatively measure and evaluate finger tapping movements for the assessment of motor function using log-linearized Gaussian mixture networks (LLGMNs). First, finger tapping movements are measured using magnetic sensors, and eleven indices are computed for evaluation. After standardizing these indices based on those of normal subjects, they are input to LLGMNs to assess motor function. Then, motor ability is probabilistically discriminated to determine whether it is normal or not using a classifier combined with the output of multiple LLGMNs based on bagging and entropy. This paper reports on evaluation and discrimination experiments performed on finger tapping movements in 33 Parkinson’s disease (PD) patients and 32 normal elderly subjects. The results showed that the patients could be classified correctly in terms of their impairment status with a high degree of accuracy (average rate: 93.1 ± 3.69%) using 12 LLGMNs, which was about 5% higher than the results obtained using a single LLGMN

The Lactic Acid Bacterium Pediococcus acidilactici Suppresses Autoimmune Encephalomyelitis by Inducing IL-10-Producing Regulatory T Cells

BACKGROUND: Certain intestinal microflora are thought to regulate the systemic immune response. Lactic acid bacteria are one of the most studied bacteria in terms of their beneficial effects on health and autoimmune diseases; one of which is Multiple sclerosis (MS) which affects the central nervous system. We investigated whether the lactic acid bacterium Pediococcus acidilactici, which comprises human commensal bacteria, has beneficial effects on experimental autoimmune encephalomyelitis (EAE), an animal model of MS. METHODOLOGY/PRINCIPAL FINDINGS: P. acidilactici R037 was orally administered to EAE mice to investigate the effects of R037. R037 treatment suppressed clinical EAE severity as prophylaxis and therapy. The antigen-specific production of inflammatory cytokines was inhibited in R037-treated mice. A significant increase in the number of CD4(+) Interleukin (IL)-10-producing cells was observed in the mesenteric lymph nodes (MLNs) and spleens isolated from R037-treated naive mice, while no increase was observed in the number of these cells in the lamina propria. Because only a slight increase in the CD4(+)Foxp3(+) cells was observed in MLNs, R037 may primarily induce Foxp3(-) IL10-producing T regulatory type 1 (Tr1) cells in MLNs, which contribute to the beneficial effect of R037 on EAE. CONCLUSIONS/SIGNIFICANCE: An orally administered single strain of P. acidilactici R037 ameliorates EAE by inducing IL10-producing Tr1 cells. Our findings indicate the therapeutic potential of the oral administration of R037 for treating multiple sclerosis

Partial suppression of M1 microglia by Janus kinase 2 inhibitor does not protect against neurodegeneration in animal models of amyotrophic lateral sclerosis

BACKGROUND: Accumulating evidence has shown that the inflammatory process participates in the pathogenesis of amyotrophic lateral sclerosis (ALS), suggesting a therapeutic potential of anti-inflammatory agents. Janus kinase 2 (JAK2), one of the key molecules in inflammation, transduces signals downstream of various inflammatory cytokines, and some Janus kinase inhibitors have already been clinically applied to the treatment of inflammatory diseases. However, the efficacy of JAK2 inhibitors in treatment of ALS remains to be demonstrated. In this study, we examined the role of JAK2 in ALS by administering a selective JAK2 inhibitor, R723, to an animal model of ALS (mSOD1(G93A) mice). FINDINGS: Orally administered R723 had sufficient access to spinal cord tissue of mSOD1(G93A) mice and significantly reduced the number of Ly6c positive blood monocytes, as well as the expression levels of IFN-γ and nitric oxide synthase 2, inducible (iNOS) in the spinal cord tissue. R723 treatment did not alter the expression levels of Il-1β, Il-6, TNF, and NADPH oxidase 2 (NOX2), and suppressed the expression of Retnla, which is one of the markers of neuroprotective M2 microglia. As a result, R723 did not alter disease progression or survival of mSOD1(G93A) mice. CONCLUSIONS: JAK2 inhibitor was not effective against ALS symptoms in mSOD1(G93A) mice, irrespective of suppression in several inflammatory molecules. Simultaneous suppression of anti-inflammatory microglia with a failure to inhibit critical other inflammatory molecules might explain this result. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12974-014-0179-2) contains supplementary material, which is available to authorized users

Disease-Association Analysis of an Inflammation-Related Feedback Loop

SummaryThe IL-6-triggered positive feedback loop for NFκB signaling (or the IL-6 amplifier/Inflammation amplifier) was originally discovered as a synergistic-activation signal that follows IL-17/IL-6 stimulation in nonimmune cells. Subsequent results from animal models have shown that the amplifier is activated by stimulation of NFκB and STAT3 and induces chemokines and inflammation via an NFκB loop. However, its role in human diseases is unclear. Here, we combined two genome-wide mouse screens with SNP-based disease association studies, revealing 1,700 genes related to the IL-6 amplifier, 202 of which showed 492 indications of association with ailments beyond autoimmune diseases. We followed up on ErbB1 from our list. Blocking ErbB1 signaling suppressed the IL-6 amplifier, whereas the expression of epiregulin, an ErbB1 ligand, was higher in patients with inflammatory diseases. These results indicate that the IL-6 amplifier is indeed associated with human diseases and disorders and that the identified genes may make for potential therapeutic targets

Combustion characteristics of Mg vapor jet flames in CO2 atmospheres

An experimental study was performed on the combustion characteristics of a jet diffusion flame of Mg vapor injected through a small nozzle into CO2 atmospheres at low pressures from 8 to 48 kPa with a view to using Mg as fuel for a CO2-breathing turbojet engine in the Mars atmosphere. The Mg vapor jet produced three types of the flame. At lower pressures and higher injection velocities, a red-heated jet flame formed, in which the injected Mg vapor was heated by spontaneous reactions, turning red. At medium pressures and injection velocities, a stable luminous lifted-like flame developed above the rim of the chimney, a tube-like combustion product for the Mg vapor passage that grew on the nozzle during combustion. The flame had similar flame length properties to laminar jet diffusion flames of gaseous fuels. At higher pressures and lower injection velocities, a stable luminous attached flame developed at the rim of the chimney. The same reactions, producing MgO(g), CO and MgO(c), proceeded preferentially for all flames and chimneys. Carbon was only subordinately generated. Burning behavior of Mg vapor jets in a CO2 atmosphere has been represented, including the homogeneous reaction of Mg vapor with CO2, the diffusion of CO2, and the condensation and deposit of MgO. The injection velocity of Mg vapor at the rim of the chimney and the exothermic reactions with diffused CO2 that occur there play a crucial role in the attachment and development of the flames. The flame structure may be explained in terms of the relatively low gas-phase reaction rate of Mg with CO2