Development, Test and Validation of a Mechatronic Device for Spasticity Quantification

Abstract Spasticity is a common pathological phenomenon in clinical practices, frequently expressed as a stroke, multiple sclerosis or cerebral palsy. The accurate quantification of spasticity allows early action to prevent the potentially irreversible consequences. The aim of this work is to develop and implement a mechatronic device for the accurate quantification of spasticity, which is able to differentiate spasticity from other motor disorders. The proposed method is based on the quantification of the tonic stretch reflex threshold (TSRT) for the assessment of the range of motion of the limb affected by spasticity. In order to validate the developed device, experimental trials have been conducted, considering the flexor muscle of the elbow joint. The developed device was tested, first in a laboratory environment with healthy subjects and secondly, in a clinical environment with the collaboration of patients with spasticity. The evaluations in th clinical environment were performed on three different days in order to evaluate the reproducibility of the obtained results. The experimental trials confirm the sensibility, reproducibility and reliability of spasticity quantification based on the TSRT method. This project has been developed in cooperation with the Hospital of Braga and Fisimaia rehabilitation clinic, both in Portugal

Inv21p12q22del21q22 and intellectual disability

Chromosomal rearrangements are common in humans. Pericentric inversions are among the most frequent aberrations (1-2%). Most inversions are balanced and do not cause problems in carriers unless one of the breakpoints disrupts important functional genes, has near submicroscopic copy number variants or hosts "cryptic" complex chromosomal rearrangements. Pericentric inversions can lead to imbalance in offspring. Less than 3% of Down syndrome patients have duplication as a result of parental pericentric inversion of chromosome 21. We report a family with an apparently balanced pericentric inversion of chromosome 21. The proband, a 23-year-old female was referred for prenatal diagnosis at 16weeks gestation because of increased nuchal translucency. She has a familial history of Down's syndrome and moderate intellectual disability, a personal history of four spontaneous abortions and learning difficulties. Peripheral blood and amniotic fluid samples were collected to perform proband's and fetus' cytogenetic analyses. Additionally, another six family members were evaluated and cytogenetic analysis was performed. Complementary FISH and MLPA studies were carried out. An apparent balanced chromosome 21 pericentric inversion was observed in four family members, two revealed a recombinant chromosome 21 with partial trisomy, and one a full trisomy 21 with an inverted chromosome 21. Array CGH analysis was performed in the mother and the brother's proband. MLPA and aCGH studies identified a deletion of about 1.7Mb on the long arm of inverted chromosome 21q22.11. We believe the cause of the intellectual disability/learning difficulties observed in the members with the inversion is related to this deletion. The recombinant chromosome 21 has a partial trisomy including the DSCR with no deletion. The risk for carriers of having a child with multiple malformations/intellectual disability is about 30% depending on whether and how this rearrangement interferes with meiosis

MiR-155 has a protective role in the development of non-alcoholic hepatosteatosis in mice

Hepatic steatosis is a global epidemic that is thought to contribute to the pathogenesis of type 2 diabetes. MicroRNAs (miRs) are regulators that can functionally integrate a range of metabolic and inflammatory pathways in liver. We aimed to investigate the functional role of miR-155 in hepatic steatosis. Male C57BL/6 wild-type (WT) and miR-155−/− mice were fed either normal chow or high fat diet (HFD) for 6 months then lipid levels, metabolic and inflammatory parameters were assessed in livers and serum of the mice. Mice lacking endogenous miR-155 that were fed HFD for 6 months developed increased hepatic steatosis compared to WT controls. This was associated with increased liver weight and serum VLDL/LDL cholesterol and alanine transaminase (ALT) levels, as well as increased hepatic expression of genes involved in glucose regulation (Pck1, Cebpa), fatty acid uptake (Cd36) and lipid metabolism (Fasn, Fabp4, Lpl, Abcd2, Pla2g7). Using miRNA target prediction algorithms and the microarray transcriptomic profile of miR-155−/− livers, we identified and validated that Nr1h3 (LXRα) as a direct miR-155 target gene that is potentially responsible for the liver phenotype of miR-155−/− mice. Together these data indicate that miR-155 plays a pivotal role regulating lipid metabolism in liver and that its deregulation may lead to hepatic steatosis in patients with diabetes

Enrichment of sulphate-reducers and depletion of butyrate-producers may be hyperglycaemia signatures in the diabetic oral microbiome

Objectives This study aimed to investigate oral microbial signatures associated with hyperglycaemia, by correlating the oral microbiome with three glycaemic markers. Potential association between clinical parameters and oral bacterial taxa that could be modulating the hyperglycaemic microbiome was also explored. Methods Twenty-three individuals diagnosed with type 2 Diabetes Mellitus (T2D) and presenting periodontitis were included, as well as 25 systemically and periodontally healthy ones. Fasting blood glucose, glycated haemoglobin, salivary glucose, periodontitis classification, caries experience and activity and salivary pH were evaluated. The V4 region of the 16S rRNA gene was amplified from total salivary DNA, and amplicons were sequenced (Illumina MiSeq). Results Hyperglycaemia was correlated with proportions of Treponema, Desulfobulbus, Phocaiecola and Saccharimonadaceae. Desulfobulbus was ubiquitous and the most enriched organism in T2D individuals (log2FC = 4). The Firmicutes/Bacteroidetes ratio was higher at alkali salivary pH than acidic pH. In the network analysis, Desulfobulbus was clustered in a negative association with caries-associated and butyrate-producing bacteria. Conclusion The salivary microbiome is shaped by systemic hyperglycaemia, as well as changes in the salivary pH, which may be linked to local hyperglycaemia. The enrichment of predictive biomarkers of gut dysbiosis in the salivary microbiome can reflect its capacity for impairment of hyperglycaemia

Heparan sulfate and heparin interactions with proteins.

Heparan sulfate (HS) polysaccharides are ubiquitous components of the cell surface and extracellular matrix of all multicellular animals, whereas heparin is present within mast cells and can be viewed as a more sulfated, tissuespecific, HS variant. HS and heparin regulate biological processes through interactions with a large repertoire of proteins. Owing to these interactions and diverse effects observed during in vitro, ex vivo and in vivo experiments, manifold biological/pharmacological activities have been attributed to them. The properties that have been thought to bestow protein binding and biological activity upon HS and heparin vary from high levels of sequence specificity to a dependence on charge. In contrast to these opposing opinions, we will argue that the evidence supports both a level of redundancy and a degree of selectivity in the structure–activity relationship. The relationship between this apparent redundancy, the multi-dentate nature of heparin and HS polysaccharide chains, their involvement in protein networks and the multiple binding sites on proteins, each possessing different properties, will also be considered. Finally, the role of cations in modulating HS/heparin activity will be reviewed and some of the implications for structure–activity relationships and regulation will be discussed

Stellar Coronal and Wind Models: Impact on Exoplanets

Surface magnetism is believed to be the main driver of coronal heating and stellar wind acceleration. Coronae are believed to be formed by plasma confined in closed magnetic coronal loops of the stars, with winds mainly originating in open magnetic field line regions. In this Chapter, we review some basic properties of stellar coronae and winds and present some existing models. In the last part of this Chapter, we discuss the effects of coronal winds on exoplanets.Comment: Chapter published in the "Handbook of Exoplanets", Editors in Chief: Juan Antonio Belmonte and Hans Deeg, Section Editor: Nuccio Lanza. Springer Reference Work

Calculating the energy spectra of magnetic molecules: application of real- and spin-space symmetries

The determination of the energy spectra of small spin systems as for instance given by magnetic molecules is a demanding numerical problem. In this work we review numerical approaches to diagonalize the Heisenberg Hamiltonian that employ symmetries; in particular we focus on the spin-rotational symmetry SU(2) in combination with point-group symmetries. With these methods one is able to block-diagonalize the Hamiltonian and thus to treat spin systems of unprecedented size. In addition it provides a spectroscopic labeling by irreducible representations that is helpful when interpreting transitions induced by Electron Paramagnetic Resonance (EPR), Nuclear Magnetic Resonance (NMR) or Inelastic Neutron Scattering (INS). It is our aim to provide the reader with detailed knowledge on how to set up such a diagonalization scheme.Comment: 29 pages, many figure

Modulation of Experimental Herpes Encephalitis-Associated Neurotoxicity through Sulforaphane Treatment

Reactive oxygen species (ROS) produced by brain-infiltrating macrophages and neutrophils, as well as resident microglia, are pivotal to pathogen clearance during viral brain infection. However, unchecked free radical generation is also responsible for damage to and cytotoxicity of critical host tissue bystander to primary infection. These unwanted effects of excessive ROS are combated by local cellular production of antioxidant enzymes, including heme oxygenase-1 (HO-1) and glutathione peroxidase 1 (Gpx1). In this study, we showed that experimental murine herpes encephalitis triggered robust ROS production, as well as an opposing upregulation of the antioxidants HO-1 and Gpx1. This antioxidant response was insufficient to prevent tissue damage, neurotoxicity, and mortality associated with viral brain infection. Previous studies corroborate our data supporting astrocytes as the major antioxidant producer in brain cell cultures exposed to HSV-1 stimulated microglia. We hypothesized that stimulating opposing antioxidative responses in astrocytes, as well as neurons, would mitigate the effects of ROS-mediated neurotoxicity both in vitro and during viral brain infection in vivo. Here, we demonstrate that the addition of sulforaphane, a potent stimulator of antioxidant responses, enhanced HO-1 and Gpx1 expression in astrocytes through the activation of nuclear factor-E2-related factor 2 (Nrf2). Additionally, sulforaphane treatment was found to be effective in reducing neurotoxicity associated with HSV-stimulated microglial ROS production. Finally, intraperitoneal injections of sulforaphane into mice during active HSV infection reduced neuroinflammation via a decrease in brain-infiltrating leukocytes, macrophage- and neutrophil-produced ROS, and MHCII-positive, activated microglia. These data support a key role for astrocyte-produced antioxidants in modulating oxidative stress and neuronal damage in response to viral infection

Nocardia transvalensis keratitis: an emerging pathology among travelers returning from Asia

<p>Abstract</p> <p>Background</p> <p>The incidence rate of <it>Nocardia </it>keratitis is increasing, with new species identified thanks to molecular methods. We herein report a case of <it>Nocardia transvalensis </it>keratitis, illustrating this emerging pathology among travellers returning from Asia.</p> <p>Case presentation</p> <p>A 23-year-old man presented with a 10-week history of ocular pain, redness, and blurred vision in his right eye following a projectile foreign body impacting the cornea while motor biking in Thaïland. At presentation, a central epithelial defect with a central whitish stromal infiltrate associated with pinhead satellite infiltrates was observed. Identification with 16S rRNA PCR sequencing and microbiological culture of corneal scraping and revealed <it>N. transvalensis </it>as the causative organism. Treatment was initiated with intensive topical amikacin, oral ketoconazole and oral doxycycline. After a four-week treatment period, the corneal infiltrate decreased so that only a faint subepithelial opacity remained.</p> <p>Conclusion</p> <p><it>Nocardia </it>organisms should be suspected as the causative agent of any case of keratitis in travelers returning from Asia. With appropriate therapy, <it>Nocardia </it>keratitis resolves, resulting in good visual outcome.</p