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In this chapter, we present some of the common comorbidities frequently encountered in persons with epilepsy (PWE). We begin by examining the cognitive and behavioral issues, then focus on sleep disorders, headaches, and bone health, and end by discussing the topic of sudden unexpected death in epilepsy (SUDEP). We hope that this chapter will assist physicians in providing better care to PWE.
Recent studies reveal that at large friction Reynolds number
the inertially dominated region of the turbulent boundary layer is composed of large-scale zones of nearly uniform momentum segregated by narrow fissures of concentrated vorticity. Experiments show that, when scaled by the boundary-layer thickness, the fissure thickness is
, while the dimensional jump in streamwise velocity across each fissure scales in proportion to the friction velocity
. A simple model that exploits these essential elements of the turbulent boundary-layer structure at large
is developed. First, a master wall-normal profile of streamwise velocity is constructed by placing a discrete number of fissures across the boundary layer. The number of fissures and their wall-normal locations follow scalings informed by analysis of the mean momentum equation. The fissures are then randomly displaced in the wall-normal direction, exchanging momentum as they move, to create an instantaneous velocity profile. This process is repeated to generate ensembles of streamwise velocity profiles from which statistical moments are computed. The modelled statistical profiles are shown to agree remarkably well with those acquired from direct numerical simulations of turbulent channel flow at large
. In particular, the model robustly reproduces the empirically observed sub-Gaussian behaviour for the skewness and kurtosis profiles over a large range of input parameters.
Glioblastoma is considered among the most aggressive cancers, dismal prognosis and overall survival is only 14 months, 80% of primary low grade gliomas and seccondary GBMs that progress from low grade to grade II or III WHO classification have isocitrate dehydrogenase, (IDH1) or IDH2, mutations . IDH1 mutant glioma is characterized by impaired glycolysis activity resulting in an abnormal production of 2-hydroxyglutarate (2-HG)  resulting in an undifferentiated phenotype with permanent hyper-methylation status and enhanced proliferation and invasion. Interestingly, the IDH1 mutant phenotype of U87MG glioma cells shows resistance to autophagy induced cell death even in starving and low oxygen conditions . Recent evidence has demonstrated increased autophagy activity on IDH1 mt cytotoxic activity when cells are exposed to autophagy inhibitors such as chloroquine . To this date it remains elusive whether increased autophagy phenotype is the result of IDH1 mutation or if it either represents a secondary co-existing condition in the setting of the IDH1 mutation. Autophagy is also a mechanism of detoxification induced by chronic heavy metal exposure in both normal and cancer cells. Thus, we hypothesized that autophagy activity in IDH1 mt glioma is partially induced by chronic heavy metal exposure, leading to increased cell survival and abnormal DNA repair. Our approach included characterization and quantification of metal content on IDH1 mt glioma cell lines and tissues, in addition to correlation analyses of the celullar metallome with autophagy markers, ROS and DNA repair of IDH1 mt glioma cells allowed us to explore targets responsible for cell survival and DNA repair response. Furthermore, we evaluated the potential therapeutic value of Chloroquine (CQ) and bafylomicin for IDH1 mutant gliomas targeting autophagy pathway in combination with TMZ and radiation. We demonstrated that 2-HG induces autophagy activity via LC3B activation, and autophagy inhibiton by beclin gene silencing results in a reduction of 2-HG leading to cell starvation and apoptosis. Remarkably, we observed a positive correlation on at least six different metals with autophagy induced LC3B and beclin1 expression that significantly differed between the mutant and the wt genotype in glioma cell lines. ROS and DNA repair were also positively associated with at least 6 different metals and only seen in the IDH1 mt cell lines, then suggesting a possible explanation for the increase on autophagy, analysis of both LC3B and beclin 1 expression demonstrated a positive correlation with Mo98, Fe54, and Zn 66 on IDH1 mt cell lines and a positively correlation with Mo98 and V concentrations in relation to H2AX expression. Co, SeO Mo, V and Mg were positively correlated to ROS expression. TMZ and CQ induced autophagy pathway activation as measured by LC3B, Beclin, Atg expression. Silencing beclin in IDH1 mutant glioma cell lines induced apoptosis and reduction on 2-HG production after treatment with TMZ and radiation. Overall the results contained in this study 1) identify cellular metal content in relationship to mechanisms leading to increased autophagy on IDH1 mt glioma cells. 2) evaluate the combination of CQ and TMZ to potentially target and inhibit autophagy as a mechanism downstream the 2-HG production in IDH1 mt glioma cells.
The circadian disruption in shift-workers is suggested to be a risk factor to develop overweight and metabolic dysfunction. The conflicting time signals given by shifted activity, shifted food intake and exposure to light at night occurring in the shift-worker are proposed to be the cause for the loss of internal synchrony and the consequent adverse effects on body weight and metabolism. Because food elicited signals have proven to be potent entraining signals for peripheral oscillations, here we review the findings from experimental models of shift-work and verify whether they provide evidence about the causal association between shifted feeding schedules, circadian disruption and altered metabolism. We found mainly four experimental models that mimic the conditions of shift-work: protocols of forced sleep deprivation, of forced activity during the normal rest phase, exposure to light at night and shifted food timing. A big variability in the intensity and duration of the protocols was observed, which led to a diversity of effects. A common result was the disruption of temporal patterns of activity; however, not all studies explored the temporal patterns of food intake. According to studies that evaluate time of food intake as an experimental model of shift-work and studies that evaluate shifted food consumption, time of food intake may be a determining factor for the loss of balance at the circadian and metabolic level.
The Nevado de Toluca is a stratovolcano located in the southwest of the Toluca Valley in central Mexico. At a height of around 4200 m there are two crater lakes: El Sol and La Luna. Since Precolumbian times, people in the surrounding valleys carried out rituals and deposited offerings into the lakes. After the Spanish conquest, these rituals were kept alive clandestinely. Currently, reminiscent of Mesoamerican rituals subsist. Due to the long duration of the ritual at the Nevado de Toluca, it is important to date the materials recovered in the underwater and terrestrial archaeological explorations. This article proposes a chronology of Prehispanic ritual activities performed in the Nevado de Toluca based on the characterization and radiocarbon (14C) dating performed to materials from the volcano’s lakes.
Two metal fillers with TiC nanoparticles (TiC NPs) of less than 100 nm for the overlay process is an alternative to hardfacing for treating surfaces subjected to severe wear. In this work, the effect of tribological behavior for TiC NPs addition on two Co-based filler materials, as well as the dilutions, was studied. Mixtures of Co-based filler metals without and with 0.5% and 2% TiC NPs were deposited onto D2 steel plates using PTA (Plasma Transferred Arc). The BET surface area was 0.17 m2 g-1 and 0.31 m2 g-1, respectively, for Stellite 6 and 12. The distribution of ca 23% macroporous for Stellite 6 was sufficient to get inside the TiC NPs, as well as in the case of Stellite 12, with a pore distribution of ca 13%. Stellite 12 has an increase in the dilutions (70%) and enthalpies showed endothermic reactions. Stellite 6 with NPs was determined to be most effective in increasing the wear resistance.
In this work, the effect of three principal and independent parameters of Atmospheric Plasma Spray on the properties of coatings deposited using mixtures of commercial powders of titanium dioxide (TiO2) and chromium oxide (Cr2O3) was studied. The results of this work are used for special applications on turbomachinery components such as wear protection in sliding seals and in steam valves for turbines, chemical protection for centrifugal compressor members, and special seal applications.
The design of experiments (DoE) technique has proved to be very useful to study the influence factors and optimization. Pierlot et al.  demonstrated that the application of the Hadamard and two factorial design techniques are useful for the optimization of thermal spray processes. An example of the application of the DoE is the one mentioned by Murugan et al. . In their work, a factorial design was used to study the interactions between gas flow, oxygen flow, powder rate and spray distance on the percentage of porosity and hardness of TiO2 - Cr2O3 composite coatings generated by High Velocity Oxy-Fuel.
The ½ fractional two-level factorial DoE technique was used to analyze and optimize the Atmospheric Plasma Spray process parameters. In the current research, experiments were conducted varying the deposition velocity, gas flow and stand-off distance. The effect of these process variables were evaluated by thickness, hardness and microstructure analysis. In this study, an empirical relationship between process variables and response parameters was developed. The entire relationship was made using the results of the DoE.
Stegophorus macronectes (Johnston & Mawson, 1942) is a gastrointestinal parasite found in Antarctic seabirds. The original description of the species, which was based only on females, is poor and fragmented with some unclear diagnostic characters. This study provides new morphometric and molecular data on this previously poorly described parasite. Nuclear rDNA sequences (18S, 5.8S, 28S and internal transcribed spacer (ITS) regions) were isolated from S. macronectes specimens collected from the chinstrap penguin Pygoscelis antarctica Forster on Deception Island, Antarctica. Using 18S rDNA sequences, phylogenetic analyses (maximum likelihood, maximum parsimony and Bayesian inference) of the order Spirurida were performed to determine the phylogenetic location of this species. Primer pairs of the ITS regions were designed for genus-level identification of specimens, regardless of their cycle, as an alternative to coprological methods. The utility of this molecular method for identification of morphologically altered specimens is also discussed.
High protein intake in early childhood is associated with obesity, suggesting possible adverse effects on other cardiometabolic outcomes. However, studies in adults have suggested beneficial effects of protein intake on blood pressure (BP) and lipid profile. Whether dietary protein intake is associated with cardiovascular and metabolic health in children is unclear. Therefore, we aimed to systematically review the evidence on the associations of protein intake with BP, insulin sensitivity and blood lipids in children. We searched the databases Medline, Embase, Cochrane Central and PubMed for interventional and observational studies in healthy children up to the age of 18 years, in which associations of total, animal and/or vegetable protein intake with one or more of the following outcomes were reported: BP; measures of insulin sensitivity; cholesterol levels; or TAG levels. In the search, we identified 6636 abstracts, of which fifty-six studies met all selection criteria. In general, the quality of the included studies was low. Most studies were cross-sectional, and many did not control for potential confounders. No overall associations were observed between protein intake and insulin sensitivity or blood lipids. A few studies suggested an inverse association between dietary protein intake and BP, but evidence was inconclusive. Only four studies examined the effects of vegetable or animal protein intake, but with inconsistent results. In conclusion, the literature, to date provides insufficient evidence for effects of protein intake on BP, insulin sensitivity or blood lipids in children. Future studies could be improved by adequately adjusting for key confounders such as energy intake and obesity.
Treatment options for epilepsy have increased in the last decade with the introduction of several new antiepileptic drugs (AEDs). As drug selection becomes more challenging, the use of evidence-based guidelines to aid in treatment decisions has become increasingly valued. The American Academy of Neurology's (AAN) guidelines for the use of new AEDs in refractory epilepsy offers many benefits, including expert panel recommendations based on clinically relevant questions with evidence-based responses. However, lack of evidence from randomized-controlled trials, particularly as they relate to monotherapy, limits the recommendations and their use in practice. The studies of new AEDs as monotherapy in treatment-refractory epilepsy are difficult to incorporate into clinical use because they are driven by Food and Drug Administration requirements to show superiority over placebo or pseudoplacebo (ie, low dose of active drug) rather than by clinical questions. However, based on Class I evidence, the AAN guidelines have granted Level A recommendations (established effectiveness) for oxcarbazepine and topiramate monotherapy, and a Level B recommendation (probable effectiveness) for lamotrigine monotherapy in the use of refractory partial epilepsy. There is insufficient evidence to recommend gabapentin, levetiracetam, tiagabine, or zonisamide monotherapy. No monotherapy AED trials have been conducted in refractory generalized epilepsy. Because no differences in efficacy have been reported for AEDs as initial therapy of partial seizures, differences in adverse events, such as weight gain, tremor, and hair loss, are key in drug selection. More comparative studies between the AEDs are necessary for both monotherapy and add-on therapy for treatment-refractory epilepsy.
Spectroscopy of planetary nebulae (PNe) provides the means to investigate s-process enrichments of neutron(n)-capture elements that cannot be detected in Asymptotic Giant Branch (AGB) stars. However, accurate abundance determinations of these elements present a challenge. Corrections for unobserved ions can be large and uncertain, since in many PNe only one ion of a given n-capture element has been detected. Furthermore, the atomic data governing the ionization balance of these species are not well-determined, inhibiting the derivation of accurate ionization corrections. We present initial results of a program that addresses these challenges. Deep high-resolution optical spectroscopy of ∼20 PNe has been performed to detect emission lines from trans-iron species including Se, Br, Kr, Rb and Xe. The optical spectral region provides access to multiple ions of these elements, which reduces the magnitude and importance of uncertainties in the ionization corrections. In addition, experimental and theoretical efforts are providing determinations of the photoionization cross sections and recombination rate coefficients of Se, Kr and Xe ions. These new atomic data will make it possible to derive robust ionization corrections for these elements. Together, our observational and atomic data results will enable n-capture element abundances to be determined with unprecedented accuracy in ionized nebulae.
Silicon nanoparticles of 100 nm obtained by high-energy ball milling were characterized by X-ray diffraction (XRD) and transmission electronic microscopy (TEM). Results show dark areas due to a staking of defects. On the other hand, brighter areas exhibit a combination of small crystalline and amorphous zones. To fulfill and cover the micro-cracking and micro-pores generated during the welding process of 304 stainless steels joined by brazing, these nanoparticles were deposited directly in the fracture. The amorphous silicon drove the Transient Liquid Phase (TLP) at 1000°C for 20 min. This amorphous silicon decreases the energies of reaction between the substrate and melting filler. TLP increases the wettability and capillary forces between micro-cracking and micro-pores; due to that, the eutectic phase contained by the melting filler forms a liquid. Moreover, the weld beads were characterized by Scanning Electron Microscopy (SEM) to analyze the effect of silicon nanoparticles on the weld beads. These results showed that the interaction of the Si nanoparticles with metallic filler in the melting zone decreases the size and change the morphology of the present phases as well as the zone of isothermic growth.
The effects of bread consumption change over time on anthropometric measures have been scarcely studied. We analysed 2213 participants at high risk for CVD from the PREvención con DIeta MEDiterránea (PREDIMED) trial to assess the association between changes in the consumption of bread and weight and waist circumference gain over time. Dietary habits were assessed with validated FFQ at baseline and repeatedly every year during 4 years of follow-up. Using multivariate models to adjust for covariates, long-term weight and waist circumference changes according to quartiles of change in energy-adjusted white and whole-grain bread consumption were calculated. The present results showed that over 4 years, participants in the highest quartile of change in white bread intake gained 0·76 kg more than those in the lowest quartile (P for trend = 0·003) and 1·28 cm more than those in the lowest quartile (P for trend < 0·001). No significant dose–response relationships were observed for change in whole-bread consumption and anthropometric measures. Gaining weight (>2 kg) and gaining waist circumference (>2 cm) during follow-up was not associated with increase in bread consumption, but participants in the highest quartile of changes in white bread intake had a reduction of 33 % in the odds of losing weight (>2 kg) and a reduction of 36 % in the odds of losing waist circumference (>2 cm). The present results suggest that reducing white bread, but not whole-grain bread consumption, within a Mediterranean-style food pattern setting is associated with lower gains in weight and abdominal fat.
In this study, we characterized 8 new isolates obtained from healthy but congenitally infected calves using a BALB/c mouse model. Neospora caninum-infected mice survived without exhibiting any clinical signs of disease. Nevertheless, differences among isolates in parasite organ distribution, parasite burden and the severity of histopathological lesions were determined. Mice infected with the Nc-Spain 5H, Nc-Spain 7 and Nc-Spain 9 isolates showed higher parasite burdens and more severe brain lesions during the late phase of infection compared to mice infected with the Nc-Spain 2H, Nc-Spain 3H or Nc-Spain 6 isolates. Furthermore, differences in the immunoglobulin IgG1 and IgG2a isotype kinetics induced by these isolates were observed, with a more rapid IgG2a response seen in mice infected with the Nc-Spain 2H and Nc-Spain 3H isolates. These results confirm the intra-species variability of N. caninum pathogenicity.
With the help of a modern mason, the authors have discovered a series of scarcely visible markings on well-known limestone statues from southern Spain dating back to the fifth century BC. Unrelated to letters or religious symbols, their best point of comparison seems to lie with the kind of signature used by masons to denote a craftsman or workshop. One can certainly forgive any sculptor an expression of pride in the elegant and complex carvings of the Iberian culture.
Neospora caninum is a cyst-forming parasite that causes abortion in cattle. Despite this parasite's ubiquitous distribution and wide host range, the number of N. caninum isolates obtained to date is limited. In vitro isolation of the parasite is arduous and often unsuccessful. In addition, most isolates have been obtained from clinically affected hosts and therefore could be biased towards more virulent isolates. In this report, an improved isolation approach from transplacentally infected newborn calves was undertaken and 9 new isolates were obtained. Moreover, a microsatellite technique was applied to investigate the genetic diversity of these isolates. Most isolates showed specific genetic profiles. However, the Nc-Spain10 isolate was identical to the previously described Nc-Spain1H isolate and Nc-Spain3H was identical to Nc-Spain4H. These isolates were likely to have identical genotypes because they were isolated from distinct calves of the same herd. Future pathogenic characterization of these isolates will contribute to the investigation of the relationship between isolate virulence and the outcome of infection, as well as other epidemiological features, such as transmission.