HEMIC Project: Design of a Clinical Information Modelling Tool Based on ISO13972 Technical Specification

The Andalusian Health Service is the public healthcare provider for 8.302.923 inhabitants in the South Spain. This organization coordinates primary and specialized care with an IT infrastructure composed by multiple Electronic Health Record Systems. According to the large volume of healthcare professionals involved, there is a need for providing a consistent management of information through multiple locations and systems. The HEMIC project aims to address this need developing and validating a methodology based on a software tool for standardizing information contained within EHR systems. The developed tool has been designed for supporting the participation of healthcare professionals the establishment of mechanisms for information governance. This research presents the requirements and designs for of a software tool focused on the adoption of recognized best practice in clinical information modeling. The designed tool has a Service Oriented Architecture that will be able to integrate terminology servers and repositories of clinical information models as part of the modeling process. Moreover, the defined tool organizes clinicians, IT developers and terminology experts involved in the modeling process in three levels to promote their coordination in the definition, specialization and validation of clinical information models. In order to ensure the quality of the developed clinical information models, the defined tool is based on the requirements defined in the ISO13972 Technical Specification

BDNF is a mediator of glycolytic fiber-type specification in mouse skeletal muscle

Brain-derived neurotrophic factor (BDNF) influences the differentiation, plasticity, and survival of central neurons and likewise, affects the development of the neuromuscular system. Besides its neuronal origin, BDNF is also a member of the myokine family. However, the role of skeletal muscle-derived BDNF in regulating neuromuscular physiology in vivo remains unclear. Using gain- and loss-of-function animal models, we show that muscle-specific ablation of BDNF shifts the proportion of muscle fibers from type IIB to IIX, concomitant with elevated slow muscle-type gene expression. Furthermore, BDNF deletion reduces motor end plate volume without affecting neuromuscular junction (NMJ) integrity. These morphological changes are associated with slow muscle function and a greater resistance to contraction-induced fatigue. Conversely, BDNF overexpression promotes a fast muscle-type gene program and elevates glycolytic fiber number. These findings indicate that BDNF is required for fiber-type specification and provide insights into its potential modulation as a therapeutic target in muscle diseases

The synaptic vesicle protein CSP alpha prevents presynaptic degeneration

Cysteine string protein α (CSPα)—an abundant synaptic vesicle protein that contains a DNA-J domain characteristic of Hsp40 chaperones—is thought to regulate Ca2+ channels and/or synaptic vesicle exocytosis. We now show that, in young mice, deletion of CSPα does not impair survival and causes no significant changes in presynaptic Ca2+ currents or synaptic vesicle exocytosis as measured in the Calyx of Held synapse. At 2–4 weeks of age, however, CSPα-deficient mice develop a progressive, fatal sensorimotor disorder. The neuromuscular junctions and Calyx synapses of CSPα-deficient mice exhibit increasing neurodegenerative changes, synaptic transmission becomes severely impaired, and the mutant mice die at ∼2 months of age. Our data suggest that CSPα is not essential for the normal operation of Ca2+ channels or exocytosis but acts as a presynaptic chaperone that maintains continued synaptic function, raising the possibility that enhanced CSPα function could attenuate neurodegenerative diseases

Electric-field-induced spin-flop in BiFeO3 single crystals at room-temperature

Bismuth ferrite, BiFeO3, is the only known room-temperature 'multiferroic' material. We demonstrate here, using neutron scattering measurements in high quality single crystals, that the antiferromagnetic and ferroelectric orders are intimately coupled. Initially in a single ferroelectric state, our crystals have a canted antiferromagnetic structure describing a unique cycloid. Under electrical poling, polarisation re-orientation induces a spin flop. We argue here that the coupling between the two orders may be stronger in the bulk than that observed in thin films where the cycloid is absent

Room temperature coexistence of large electric polarization and magnetic order in BiFeO3 single crystals

From an experimental point of view, room temperature ferroelectricity in BiFeO3 is raising many questions. Electric measurements made a long time ago on solid-solutions of BiFeO3 with Pb(Ti,Zr)O3 indicate that a spontaneous electric polarization exists in BiFeO3 below the Curie temperature TC=1143K. Yet in most reported works, the synthesised samples are too conductive at room temperature to get a clear polarization loop in the bulk without any effects of extrinsic physical or chemical parameters. Surprisingly, up to now there has been no report of a P(E) (polarization versus electric field) loop at room temperature on single crystals of BiFeO3. We describe here our procedure to synthesize ceramics and to grow good quality sizeable single crystals by a flux method. We demonstrate that BiFeO3 is indeed ferroelectric at room-temperature through evidence by Piezoresponse Force Microscopy and P(E) loops. The polarization is found to be large, around 60 microC/cm2, a value that has only been reached in thin films. Magnetic measurements using a SQUID magnetometer and Mossbauer spectroscopy are also presented. The latter confirms the results of NMR measurements concerning the anisotropy of the hyperfine field attributed to the magnetic cycloidal structure.Comment: 27 pages, 12 figure

Human SOD2 Modification by Dopamine Quinones Affects Enzymatic Activity by Promoting Its Aggregation: Possible Implications for Parkinson’s Disease

Mitochondrial dysfunction and oxidative stress are considered central in dopaminergic neurodegeneration in Parkinson’s disease (PD). Oxidative stress occurs when the endogenous antioxidant systems are overcome by the generation of reactive oxygen species (ROS). A plausible source of oxidative stress, which could account for the selective degeneration of dopaminergic neurons, is the redox chemistry of dopamine (DA) and leads to the formation of ROS and reactive dopamine-quinones (DAQs). Superoxide dismutase 2 (SOD2) is a mitochondrial enzyme that converts superoxide radicals to molecular oxygen and hydrogen peroxide, providing a first line of defense against ROS. We investigated the possible interplay between DA and SOD2 in the pathogenesis of PD using enzymatic essays, site-specific mutagenesis, and optical and high-field-cw-EPR spectroscopies. Using radioactive DA, we demonstrated that SOD2 is a target of DAQs. Exposure to micromolar DAQ concentrations induces a loss of up to 50% of SOD2 enzymatic activity in a dose-dependent manner, which is correlated to the concomitant formation of protein aggregates, while the coordination geometry of the active site appears unaffected by DAQ modifications. Our findings support a model in which DAQ-mediated SOD2 inactivation increases mitochondrial ROS production, suggesting a link between oxidative stress and mitochondrial dysfunction