We recently described the genotype/phenotype features of all Spanish patients diagnosed with McArdle disease as of January 2011 (n = 239, prevalence of ~1/167,000) (J Neurol Neurosurg Psychiatry ...2012;83:322-8). Several caveats were however identified suggesting that the prevalence of the disease is actually higher.
We have now updated main genotype/phenotype data, as well as potential associations within/between them, of all Spanish individuals currently diagnosed with McArdle disease (December 2016).
Ninety-four new patients (all Caucasian) have been diagnosed, yielding a prevalence of ~1/139,543 individuals. Around 55% of the mutated alleles have the commonest PYGM pathogenic mutation p.R50X, whereas p.W798R and p.G205S account for 10 and 9% of the allelic variants, respectively. Seven new mutations were identified: p.H35R, p.R70C, p.R94Q, p.L132WfsX163, p.Q176P, p.R576Q, and c.244-3_244-2CA. Almost all patients show exercise intolerance, the second wind phenomenon and high serum creatine kinase activity. There is, however, heterogeneity in clinical severity, with 8% of patients being asymptomatic during normal daily life, and 21% showing limitations during daily activities and fixed muscle weakness. A major remaining challenge is one of diagnosis, which is often delayed until the third decade of life in 72% of new patients despite the vast majority (86%) reporting symptoms before 20 years. An important development is the growing proportion of those reporting a 4-year improvement in disease severity (now 34%) and following an active lifestyle (50%). Physically active patients are more likely to report an improvement after a 4-year period in the clinical course of the disease than their inactive peers (odds ratio: 13.98; 95% confidence interval: 5.6, 34.9; p < 0.001). Peak oxygen uptake is also higher in the former (20.7 ± 6.0 vs. 16.8 ± 5.3 mL/kg/min, p = 0.0013). Finally, there is no association between PYGM genotype and phenotype manifestation of the disease.
The reported prevalence of McArdle disease grows exponentially despite frequent, long delays in genetic diagnosis, suggesting that many patients remain undiagnosed. Until a genetic cure is available (which is not predicted in the near future), current epidemiologic data support that adoption of an active lifestyle is the best medicine for these patients.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
In the wake of a crime wave, 22 owners/operators of pharmacies in metropolitan Madrid, Spain, were interviewed about robberies, assaults, & robbery attempts at their facilities 1986-1988. Robbery ...with assault (using a knife) was more common than robbery without. Assaults were commonly committed by men, ages 20-30, against women employees. The perpetrators mainly sought money, & drugs secondarily. The majority of respondents blamed security in their zone as a cause of the robbery. Not all reported every robbery to the police, & few reported them to the College of Pharmacists. Safety & prevention measures to deal with this anxiety-producing state of affairs for pharmacists are identified. 4 Tables. M. Pflum
Neotropical orchid bees (Euglossini) are often cited as classic examples of trapline-foragers with potentially extensive foraging ranges. If long-distance movements are habitual, rare plants in ...widely scattered locations may benefit from euglossine pollination services. Here we report the first successful use of micro radio telemetry to track the movement of an insect pollinator in a complex and forested environment. Our results indicate that individual male orchid bees (Exaerete frontalis) habitually use large rainforest areas (at least 42–115 ha) on a daily basis. Aerial telemetry located individuals up to 5 km away from their core areas, and bees were often stationary, for variable periods, between flights to successive localities. These data suggest a higher degree of site fidelity than what may be expected in a free living male bee, and has implications for our understanding of biological activity patterns and the evolution of forest pollinators.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background.— The brain of migraineurs is hyperexcitable, particularly the occipital cortex, which is probably hypersensitive to light. Photophobia or hypersensitivity to light may be accounted for by ...an increased excitability of trigeminal, the visual pathways, and the occipital cortex.
Objective.— To study light sensitivity and photophobia by assessing the response to light stimuli with functional magnetic resonance imaging–blood oxygenation level dependent (fMRI‐BOLD) of the occipital cortex in migraineurs and in controls. Also, to try to decipher the contribution of the occipital cortex to photophobia and whether the cortical reactivity of migraineurs may be part of a constitutional (defensive) mechanism or represents an acquired (sensitization) phenomenon.
Methods.— Nineteen patients with migraine (7 with aura and 12 without aura) and 19 controls were studied with fMRI‐BOLD during 4 increasing light intensities. Eight axial image sections of 0.5 cm that covered the occipital cortex were acquired for each intensity. We measured the extension and the intensity of activation for every light stimuli. Photophobia was estimated according to a 0 to 3 semiquantitative scale of light discomfort.
Results.— Migraineurs had a significantly higher number of fMRI‐activated voxels at low (320.4 for migraineurs SD = 253.9 and 164.3 for controls SD = 102.7, P = .027) and medium‐low luminance levels (501.2 for migraineurs SD = 279.5 and 331.1 for controls SD = 194.3, P = .034) but not at medium‐high (579.5 for migraineurs SD = 201.4 and 510.2 for controls SD = 239.5, P = .410) and high light stimuli (496.2 for migraineurs SD = 216.2 and 394.7 for controls SD = 240, P = .210). No differences were found with respect to the voxel activation intensity (amplitude of the BOLD wave) between migraineurs and controls (8.98 SD = 2.58 vs 7.99 SD = 2.57, P = .25; 10.82 SD = 3.27 vs 9.81 SD = 3.19, P = .31; 11.90 SD = 3.18 vs 11.06 SD = 2.56, P = .62; 11.45 SD = 2.65 vs 10.25 SD = 2.22, P = .16). Light discomfort was higher in the group of migraineurs at all the intensities tested, but there was no correlation with the number of activated voxels in the occipital cortex and photophobia. Repetitive light stimuli failed to demonstrate a lack of habituation in migraineurs.
Conclusions.— Migraineurs during interictal periods showed hyperxcitability of the visual cortex with a wider photoresponsive area, the underlying mechanism probably being dual: constitutional‐defensive and acquired‐sensitizating.
Non-steroidal anti-inflammatory drugs constitute one of the groups most widely currently used, but show several problems for administration due to low solubility and delivery control. For this ...reason, several matrices have been tested to support them in order to overcome these drawbacks. Among them, layered double hydroxides have been used in recent years. The aim of this review is to update the current knowledge and findings on this hybrid system, namely, layered double hydroxides intercalated with different NSAIDs. The basic nature of the matrix introduces an additional advantage, i.e., to decrease ulceration damages. We have focused our review mostly on the preparation procedures, as these control, define and determine the performance of the systems in vitro and also in living organisms.
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Taxing multinationals is politically difficult because of the structural power of mobile firms within the global economy, and this structural power is expected to increase in the digital age. ...Recently however there has been a breakdown in the international corporate tax consensus that structured tax competition over the past century. A new norm of international taxation has emerged whereby states claim the right to tax corporate income based on presence in consumer markets. Our paper explains this unexpected reassertion of state power. Building on previous accounts of large-scale change in policy norms, we show how the emergence of digital business models led to a new tax consensus by setting in train a process of policy contestation that allowed countries to levy taxes on multinationals unilaterally, without fear of capital flight.
The use of different sources of evidence has been recommended in order to conduct species delimitation analyses to solve taxonomic issues. In this study, we use a maximum likelihood framework to ...combine morphological and molecular traits to study the case of Xylodon australis (Hymenochaetales, Basidiomycota) using the locate.yeti function from the phytools R package. Xylodon australis has been considered a single species distributed across Australia, New Zealand and Patagonia. Multi-locus phylogenetic analyses were conducted to unmask the actual diversity under X. australis as well as the kinship relations respect their relatives. To assess the taxonomic position of each clade, locate.yeti function was used to locate in a molecular phylogeny the X. australis type material for which no molecular data was available using morphological continuous traits. Two different species were distinguished under the X. australis name, one from Australia-New Zealand and other from Patagonia. In addition, a close relationship with Xylodon lenis, a species from the South East of Asia, was confirmed for the Patagonian clade. We discuss the implications of our results for the biogeographical history of this genus and we evaluate the potential of this method to be used with historical collections for which molecular data is not available.
This paper reviews current knowledge about the rheology and applications of highly concentrated molten polymers, focusing on hard particles with sizes ranging from several 100snm to a few microns. ...Understanding the rheological properties should assist the formulation and processing of such polymeric materials. The main factors affecting the rheological behavior of these composites are discussed, such as size distribution, nature and shape of the particles, interactions, maximum packing fraction and matrix viscosity. The matrix viscosity is a key parameter that has to be optimized to be low enough to enable the material processing and high enough to improve the dispersion. The size polydispersity of the fillers facilitates higher filling levels and decreases the melt mixture viscosity for a given filler content. The different types of interactions (viz. particle-particle, particle-matrix) are described to interpret the phenomena arising during processing better. On the other hand, mixing is of particular importance to reach high-quality dispersion and distribution of the particles in the matrix in order to obtain a homogenous mixture and desirable properties. The mixing methods and tools to characterize the degree of mixing are reviewed. The use of organic dispersants is generally necessary to improve and control the dispersion degree and flow properties. Mathematical models relating the viscosity as a function of the filler content for unimodal and bimodal highly filled suspensions are summarized. Constraints and flow instabilities often lead to non-linear rheological behavior such as wall slip, particle-binder segregation, swelling and surface instabilities phenomena; these are discussed. Finally, the latest applications for highly filled systems (such as solid propellants, flame retardancy, magnetic materials, ceramic materials, batteries, etc.) are presented as a source of inspiration for industrial improvements.
Plasma treatment is one of the methods currently used to obtain polymeric materials with surface properties appropriate to the functionality for which they were designed. However, the effects ...achieved after surface modification are not always long lasting and involve chemical and physical changes in the outermost layer. In this context, the effects of both argon and oxygen plasma on polylactic acid (PLA) films deposited on titanium were studied to determine which physical and chemical processes occur at the surface, and their duration. Regarding physical surface changes, there were scarcely any differences between both plasmas: roughness was very similar after treatments, root mean square height (Sq) being 10 times higher than the control, without plasma. Water contact angle (WCA) showed that the surface became more hydrophilic after application of the plasma, although hydrophilization was longer lasting in the case of argon treatment.
With regard to chemical changes, it was observed that the argon plasma treatment caused greater fragmentation of the polymer chains, and increased crosslinking between them. ToF-SIMS analysis made it possible to propose mechanisms to explain the formation of the fragments observed.
•Oxygen and argon treatment make the PLA surface more hydrophilic.•Ar plasma induces more long lasting hydrophilization than O2 plasma.•O2 plasma leads to new oxygen-rich, higher molecular weight species.•Ar plasma favors cross-linking and fragmentation of the polymer chains.
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