Novel homozygous GBA2 mutation in a patient with complicated spastic paraplegia

Hereditary spastic paraplegias (HSPs) are a heterogeneous group of neurological disorders characterized primarily by a pyramidal syndrome with lower limb spasticity, which can manifest as pure HSP or associated with a number of neurological or non-neurological signs (i.e., complicated HSPs). The clinical variability of HSPs is associated with a wide genetic heterogeneity, with more than eighty causative genes known. Recently, next generation sequencing (NGS) has allowed increasing genetic definition in such a heterogeneous group of disorders. We report on a 56- year-old man affected by sporadic complicated HSP consisting of a pyramidal syndrome, cerebellar ataxia, congenital cataract, pes cavus, axonal sensory-motor peripheral neuropathy and cognitive decline. Brain MRI showed cerebellar atrophy and thin corpus callosum. By NGS we found a novel homozygous biallelic c.452-1G > C mutation in the b-glucosidase 2 gene (GBA2), known to be causative for autosomal recessive hereditary spastic paraplegia type 46 (SPG46). The rarity of this inherited form besides reporting on a novel mutation, expands the genetic and clinical spectrum of SPG46 related HSP

Estimating an individual's oxygen uptake during cycling exercise with a recurrent neural network trained from easy-to-obtain inputs: A pilot study

Measurement of oxygen uptake during exercise ([Formula: see text]) is currently non-accessible to most individuals without expensive and invasive equipment. The goal of this pilot study was to estimate cycling [Formula: see text] from easy-to-obtain inputs, such as heart rate, mechanical power output, cadence and respiratory frequency. To this end, a recurrent neural network was trained from laboratory cycling data to predict [Formula: see text] values. Data were collected on 7 amateur cyclists during a graded exercise test, two arbitrary protocols (Prot-1 and -2) and an "all-out" Wingate test. In Trial-1, a neural network was trained with data from a graded exercise test, Prot-1 and Wingate, before being tested against Prot-2. In Trial-2, a neural network was trained using data from the graded exercise test, Prot-1 and 2, before being tested against the Wingate test. Two analytical models (Models 1 and 2) were used to compare the predictive performance of the neural network. Predictive performance of the neural network was high during both Trial-1 (MAE = 229(35) mlO2min-1, r = 0.94) and Trial-2 (MAE = 304(150) mlO2min-1, r = 0.89). As expected, the predictive ability of Models 1 and 2 deteriorated from Trial-1 to Trial-2. Results suggest that recurrent neural networks have the potential to predict the individual [Formula: see text] response from easy-to-obtain inputs across a wide range of cycling intensities

Interplay of the forces governing steroid hormone micropollutant adsorption in vertically-aligned carbon nanotube membrane nanopores

Vertically-aligned carbon nanotube (VaCNT) membranes allow water to conduct rapidly at low pressures and open up the possibility for water purification and desalination, although the ultralow viscous stress in hydrophobic and low-tortuosity nanopores prevents surface interactions with contaminants. In this experimental investigation, steroid hormone micropollutant adsorption by VaCNT membranes is quantified and explained via the interplay of the hydrodynamic drag and friction forces acting on the hormone, and the adhesive and repulsive forces between the hormone and the inner carbon nanotube wall. It is concluded that a drag force above 2.2 × 10$^{−3}$ pN overcomes the friction force resulting in insignificant adsorption, whereas lowering the drag force from 2.2 × 10$^{−3}$ to 4.3 × 10$^{−4}$ pN increases the adsorbed mass of hormones from zero to 0.4 ng cm$^{−2}$. At a low drag force of 1.6 × 10$^{−3}$ pN, the adsorbed mass of four hormones is correlated with the hormone−wall adhesive (van der Waals) force. These findings explain micropollutant adsorption in nanopores via the forces acting on the micropollutant along and perpendicular to the flow, which can be exploited for selectivity

Co-axial heterostructures integrating palladium/titanium dioxide with carbon nanotubes for efficient electrocatalytic hydrogen evolution

Considering the depletion of fossil-fuel reserves and their negative environmental impact, new energy schemes must point towards alternative ecological processes. Efficient hydrogen evolution from water is one promising route towards a renewable energy economy and sustainable development. Here we show a tridimensional electrocatalytic interface, featuring a hierarchical, co-axial arrangement of a palladium/titanium dioxide layer on functionalized multi-walled carbon nanotubes. The resulting morphology leads to a merging of the conductive nanocarbon core with the active inorganic phase. A mechanistic synergy is envisioned by a cascade of catalytic events promoting water dissociation, hydride formation and hydrogen evolution. The nanohybrid exhibits a performance exceeding that of stateof- the-art electrocatalysts (turnover frequency of 15000 H2 per hour at 50mVoverpotential). The Tafel slope of B130mV per decade points to a rate-determining step comprised of water dissociation and formation of hydride. Comparative activities of the isolated components or their physical mixtures demonstrate that the good performance evolves from the synergistic hierarchical structure

The PPAR-γ Agonist Pioglitazone Modulates Proliferation and Migration in HUVEC, HAOSMC and Human Arteriovenous Fistula-Derived Cells

The failure of arteriovenous fistulas (AVFs) following intimal hyperplasia (IH) increases morbidity and mortality rates in patients undergoing hemodialysis for chronic kidney disease. The peroxisome-proliferator associated receptor (PPAR-γ) may be a therapeutic target in IH regulation. In the present study, we investigated PPAR-γ expression and tested the effect of pioglitazone, a PPAR-γ agonist, in different cell types involved in IH. As cell models, we used Human Endothelial Umbilical Vein Cells (HUVEC), Human Aortic Smooth Muscle Cells (HAOSMC), and AVF cells (AVFCs) isolated from (i) normal veins collected at the first AVF establishment (T0), and (ii) failed AVF with IH (T1). PPAR-γ was downregulated in AVF T1 tissues and cells, in comparison to T0 group. HUVEC, HAOSMC, and AVFC (T0 and T1) proliferation and migration were analyzed after pioglitazone administration, alone or in combination with the PPAR-γ inhibitor, GW9662. Pioglitazone negatively regulated HUVEC and HAOSMC proliferation and migration. The effect was antagonized by GW9662. These data were confirmed in AVFCs T1, where pioglitazone induced PPAR- γ expression and downregulated the invasive genes SLUG, MMP-9, and VIMENTIN. In summary, PPAR-γ modulation may represent a promising strategy to reduce the AVF failure risk by modulating cell proliferation and migration

Il bilancio integrato per le PMI

Accanto ai capitali finanziario e produttivo, ogni impresa fonda il proprio business e il proprio successo anche su risorse intangibili, quali il capitale intellettuale, il capitale umano, il capitale sociale e relazionale ed il capitale naturale. Il tradizionale bilancio economico-finanziario, però, non è adatto a valutare e rappresentare tali risorse, poiché è stato concepito con riferimento ad un’economia industriale fondata pressoché esclusivamente su capitali tangibili; pertanto, anche avuto riguardo alla realtà delle PMI, si rende oggi necessario introdurre nuovi strumenti e nuovi indicatori per la misurazione e la rendicontazione, che siano in grado di cogliere e valorizzare anche le componenti immateriali del capitale aziendale. In questo contesto, il bilancio integrato si pone come una forma evoluta di comunicazione aziendale, finalizzata ad illustrare come strategia, governance, modello di business, rapporti con gli stakeholder, performance passate e prospettive future, rischi e opportunità consentano anche ad un’impresa di piccole e medie dimensioni di creare valore nel breve, medio e lungo termine

Molecular thermodynamics of precipitation

Using a simple theory for fluids and a simple theory for a solid, it is possible to construct a semi-quantitative corresponding-states phase diagram where a reduced temperature is plotted as a function of a reduced density. The reducing parameters are molecular size (sigma3) and molecular potential energy (&unknown;/kB); the phase diagram includes both low-density and high-density fluid regions and the solid region. These calculations apply to a pure substance or, of more interest, to a solute dissolved in a continuous solvent. The qualitative nature of the phase diagram depends strongly on the range of attractive intermolecular forces as indicated by an exponential parameter n; when coordination number z=8 and n is about 6, we obtain the usual phase diagram where the fluid-solid region lies to the right of the fluid-fluid coexistence curve. But when n is about 7 or 8, the fluid-solid region lies above the fluid-fluid coexistence curve. Applications are discussed for aqueous solutions of a colloid or a globular protein that may also contain a salt or a polymer to induce precipitation