Electromiography (EMG) plays a key role in the evaluation of patients with neuromuscular diseases. It can be considered an extension of the neurological examination. So it must be individualized and ...based on differential diagnosis. We have analized data about EMG performed in a period of four months in the Unit of Neurophysiopatology of University of Bari and Foggia. Data collected show that in this period we have received 807 EMG bookings: we have performed 604 exams (75%) of whom 405 exams had pertinence with differential diagnosis (50%), 199 (25%) had no pertinence; 203 patients (25%) did not turn up for the exam. At Neurophysiopathology of Foggia we have received 540 EMG booking: we have performed 504 neurophysiological studies. In the total amount of EMG performed 326 had pertinence (60%), 178 had no pertinence (33%) and 36 patients did not turn up for the exam (7%). Data collected show that physicians, medical practictioners, neurologists and other specialists share similar difficulties to make a correct differential diagnosis in the field of neuromuscular diseases and that EMG can be the most useful test in clarifying the diagnosis only after a correct clinical examination.
Based on extensive qualitative research carried out in Milan and Rome, Italy, among Zhejiang migrants, this paper attempts to compare the transnational strategies of migrants from the Wencheng and ...Qingtian districts, and to examine the impact of their transnational practices on their districts of origin. The striking differences in the character and scope of local development in these two districts of Southern Zhejiang province suggests the operation of factors that affect the migration-development nexus. Findings indicate major constraints and aspirations that shape the migrants' career abroad and their ability to take active part in local development. As such, there is a need to balance optimistic views of migration as an informal development policy with a sober appraisal of its limits and possible unexpected side effects.
Microwaves and spark plasma sintering (SPS) enhance sinterability. Simple electrical fields, applied by means of a pair of electrodes to bare specimens, have been shown to accelerate the rate of ...superplastic deformation, reduce the time and temperature for sintering, and to retard the rate of grain growth. By inference, the influence of electrical and electromagnetic fields on grain boundary energetics and kinetics is unmistakable. Often, in ceramics, grain boundaries are themselves endowed with space charge that can couple with externally applied fields. The frequency dependence of this coupling ranging from zero frequency to microwave frequencies is discussed. The classical approach for modeling grain growth, creep, and sintering, considers chemical diffusion (self‐diffusion) under a thermodynamic driving force, underpinned by a physical mechanism that visualizes the flow of mass transport in a way that reproduces the phenomenological observations. In all instances, the final analytical result can be separated into a product of three functions: one of the grain size, the second related to the thermodynamic driving force, and the third to the kinetics of mass transport. The influence of an electrical field on each of these functions is addressed.The fundamental mechanisms of these electrical interactions are discussed in the following ways: (i) dielectric loss and Joule heating in the crystal and at the grain boundary, (ii) the coupling between mechanical stress and the electrochemical potential of charged species, (iii) the interaction between applied electrical fields and the intrinsic fields that exist within the space charge layers, (iv) and the possibility of nucleating defect avalanches under electrical fields. We limit ourselves to ceramics that have at least some degree of ionic character. In these experiments the electrical fields range from several volts to several hundred volts per centimeter, and the power dissipation from Joule heating is of the order of several watts per cubic centimeter of the specimen. Metals, where very high current densities are obtained at relatively low applied electric fields, leading to phenomenon such as electromigration, are not considered.
2-Hydroxypropyl-beta-cyclodextrin (HPβCD) has gained recent attention as a potential therapeutic intervention in the treatment of the rare autosomal-recessive, neurodegenerative lysosomal storage ...disorder Niemann-Pick Disease Type C1 (NPC1). Notably, HPβCD formulations are not comprised of a single molecular species, but instead are complex mixtures of species with differing degrees of hydroxypropylation of the cyclodextrin ring. The degree of substitution is a critical aspect of the complex mixture as it influences binding to other molecules and thus could potentially modulate biological effects. VTS-270 (Kleptose HPB) and Trappsol® Cyclo™ are HPβCD products under investigation as novel treatments for NPC1. The purpose of the present work is to compare these two different products; analyses were based on ion distribution and abundance profiles using mass spectrometry methodology as a means for assessing key molecular distinctions between products. The method incorporated electrospray ionization and analysis with a linear low-field ion mobility quadrupole time-of-flight instrument. We observed that the number of hydroxypropyl groups (the degrees of substitution) are substantially different between the two products and greater in Trappsol Cyclo than in VTS-270. The principal ions of both samples are ammonium adducts. Isotope clusters for each of the major ions show doubly charged homodimers of the ammonium adducts. In addition, both products show doubly charged homodimers from adduction of both a proton and ammonium. Doubly charged heterodimers are also present, but are more intense in Trappsol Cyclo than in VTS-270. Based on the analytical differences observed between VTS-270 and Trappsol Cyclo with respect to the degree of substitution, the composition and fingerprint of the complex mixture, and the impurity profiles, these products cannot be considered to be the same; the potential biological and clinical implications of these differences are not presently known.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Flash sintering of strontium titanate (SrTiO3) is studied at different applied fields to understand its effect on density and grain growth. In particular, the defect structure is investigated by ...optical and structural analysis. SrTiO3 exhibited a trend in densification opposite that of ionically or electronically conductive ceramics: as the applied voltage decreased, the density increased. Abnormal grain growth in conventionally sintered SrTiO3 is arrested by flash sintering. Interestingly, undoped SrTiO3 behaved differently than undoped Al2O3, which did not exhibit any signs of flash sintering. Previous attempts at flash sintering could only be achieved in MgO‐doped Al2O3. We believe that non‐stoichiometric Ruddlesden‐Popper phases in SrTiO3, as indicated by ultrafast optical spectroscopy, X‐ray diffraction, conductivity measurements, and transmission electron microscopy, assist flash sintering by increasing local conductivity through enhanced defect content.
Microtubule actin crosslinking factor 1 (MACF1) plays a role in the coordination of microtubules and actin in multiple cellular processes. Here, we show that MACF1 is also critical for ciliogenesis ...in multiple cell types. Ablation of Macf1 in the developing retina abolishes ciliogenesis, and basal bodies fail to dock to ciliary vesicles or migrate apically. Photoreceptor polarity is randomized, while inner retinal cells laminate correctly, suggesting that photoreceptor maturation is guided by polarity cues provided by cilia. Deletion of MACF1 in adult photoreceptors causes reversal of basal body docking and loss of outer segments, reflecting a continuous requirement for MACF1 function. MACF1 also interacts with the ciliary proteins MKKS and TALPID3. We propose that a disruption of trafficking across microtubles to actin filaments underlies the ciliogenesis defect in cells lacking MACF1 and that MKKS and TALPID3 are involved in the coordination of microtubule and actin interactions.
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•MACF1 is required for apical basal body docking and ciliogenesis•MACF1 is critical for maintenance of the photoreceptor sensory cilium•Primary cilia may provide positional cues for apicobasal polarization of photoreceptors
May-Simera et al. find that MACF1, a giant protein that mediates microtubule and actin interactions, is essential for ciliogenesis and maintenance. In the developing retina, MACF1 is required for establishing apicobasal polarity in photoreceptors, thus highlighting the importance of cilia in providing the correct positional cues.
Anomalous aggregation of α-synuclein (α-Syn) is a pathological hallmark of many degenerative synucleinopathies including Lewy body dementia (LBD) and Parkinson’s disease (PD). Despite its strong link ...to disease, the precise molecular mechanisms that link α-Syn aggregation to neurodegeneration have yet to be elucidated. Here, we find that elevated α-Syn leads to an increase in the plasma membrane (PM) phosphoinositide PI(4,5)P2, which precipitates α-Syn aggregation and drives toxic increases in mitochondrial Ca2+ and reactive oxygen species leading to neuronal death. Upstream of this toxic signaling pathway is PIP5K1γ, whose abundance and localization is enhanced at the PM by α-Syn-dependent increases in ARF6. Selective inhibition of PIP5K1γ or knockout of ARF6 in neurons rescues α-Syn aggregation and cellular phenotypes of toxicity. Collectively, our data suggest that modulation of phosphoinositide metabolism may be a therapeutic target to slow neurodegeneration for PD and other related neurodegenerative disorders.
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•α-Syn fibrils facilitate ARF6-PIP5K1γ increases in PI(4,5)P2•α-Syn-driven increases in PI(4,5)P2 represent a key proximal step in α-Syn aggregation•α-Syn elevations in PI(4,5)P2 increase mitochondrial Ca2+ to drive neuronal cytotoxicity
α-Synuclein (α-Syn) aggregation is a key feature of neurodegenerative disorders like Lewy body dementia and Parkinson’s disease. Horvath et al. demonstrate that α-Syn fibrils or disease mutations increase the membrane phosphoinositide PI(4,5)P2, which influences α-Syn aggregation and leads to increases in mitochondrial Ca2+ and reactive oxygen species, causing neuronal death.
Niemann‐Pick, type C1 (NPC1) is a fatal, neurodegenerative disease, which belongs to the family of lysosomal diseases. In NPC1, endo/lysosomal accumulation of unesterified cholesterol and ...sphingolipids arise from improper intracellular trafficking resulting in multi‐organ dysfunction. With the proximity between the brain and cerebrospinal fluid (CSF), performing differential proteomics provides a means to shed light to changes occurring in the brain. In this study, CSF samples obtained from NPC1 individuals and unaffected controls were used for protein biomarker identification. A subset of these individuals with NPC1 are being treated with miglustat, a glycosphingolipid synthesis inhibitor. Of the 300 identified proteins, 71 proteins were altered in individuals with NPC1 compared to controls including cathepsin D, and members of the complement family. Included are a report of 10 potential markers for monitoring therapeutic treatment. We observed that pro‐neuropeptide Y (NPY) was significantly increased in NPC1 individuals relative to healthy controls; however, individuals treated with miglustat displayed levels comparable to healthy controls. In further investigation, NPY levels in a NPC1 mouse model corroborated our findings. We posit that NPY could be a potential therapeutic target for NPC1 due to its multiple roles in the central nervous system such as attenuating neuroinflammation and reducing excitotoxicity.
Thorium dioxide is a refractory ceramic material and is difficult to sinter to high density. Commercial powder starts to sinter in SPS under 70MPa above 1000°C and compaction is not finished at ...1600°C. In contrast, a 13nm nanopowder synthesised via low temperature decomposition of thorium oxalate starts to sinter at ∼500°C; the onset of sintering shifts to higher temperatures for powders with larger crystallites. The initial crystallite size solely affects the onset of sintering, whereas the final stage of sintering is independent of the initial crystallite size for the powders used in this study. Pellets with density well above 95% of the theoretical density were prepared using SPS at sintering temperature of 1600°C, 70MPa pressure and 10min dwell time.
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