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Femoral vein access is the first choice for percutaneous atrial septal defect closure, and when it cannot be used due to anatomic reasons, the alternative sites should be considered, frequently increasing the complexity of the procedure. Here we report the case of a 3-year-old boy, with situs inversus and dextrocardia, electively referred for percutaneous closure of an ostium secundum atrial septal defect. During the procedure, agenesis of the infra-hepatic segment of the inferior caval vein was diagnosed, and no double inferior caval vein or right superior caval vein were identified by ultrasound or angiography. Therefore, we opted to perform the procedure through the left internal jugular vein, with fluoroscopy and transesophageal echocardiographic guidance. Catheters were navigated through a hydrophilic guidewire, and a Stiff guidewire was positioned in the left ventricle for better support. An Amplatzer septa occluder 19 was successfully deployed without major difficulties and the patient was discharged after 24 hours in good clinical condition. Percutaneous atrial septal defect closure through alternative access sites, especially in the presence of situs inversus, may pose significant challenges to the interventional team. In this case, the left internal jugular vein has shown to be a feasible option, allowing the navigation and manipulation of devices without complications. Provided the expertise of the interventional team, and awareness of the risks involved, alternative access sites can be successfully used for paediatric structural interventions.
Survival and infectivity of trypanosomatids rely on cell-surface and secreted glycoconjugates, many of which contain a variable number of galactose residues. Incorporation of galactose to proteins and lipids occurs along the secretory pathway from UDP-galactose (UDP-Gal). Before being used in glycosylation reactions, however, this activated sugar donor must first be transported across the endoplasmic reticulum and Golgi membranes by a specific nucleotide sugar transporter (NST). In this study, we identified an UDP-Gal transporter (named TcNST2 and encoded by the TcCLB.504085.60 gene) from Trypanosoma cruzi, the etiological agent of Chagas disease. TcNST2 was identified by heterologous expression of selected putative nucleotide sugar transporters in a mutant Chinese Hamster Ovary cell line. TcNST2 mRNA levels were detected in all T. cruzi life-cycle forms, with an increase in expression in axenic amastigotes. Confocal microscope analysis indicated that the transporter is specifically localized to the Golgi apparatus. A three-dimensional model of TcNST2 suggested an overall structural conservation as compared with members of the metabolite transporter superfamily and also suggested specific features that could be related to its activity. The identification of this transporter is an important step toward a better understanding of glycoconjugate biosynthesis and the role NSTs play in this process in trypanosomatids.
The English auxiliary system exhibits many lexical exceptions and subregularities, and considerable dialectal variation, all of which are frequently omitted from generative analyses and discussions. This paper presents a detailed, movement-free account of the English Auxiliary System within Sign-Based Construction Grammar (Sag 2010, Michaelis 2011, Boas & Sag 2012) that utilizes techniques of lexicalist and construction-based analysis. The resulting conception of linguistic knowledge involves constraints that license hierarchical structures directly (as in context-free grammar), rather than by appeal to mappings over such structures. This allows English auxiliaries to be modeled as a class of verbs whose behavior is governed by general and class-specific constraints. Central to this account is a novel use of the feature aux, which is set both constructionally and lexically, allowing for a complex interplay between various grammatical constraints that captures a wide range of exceptional patterns, most notably the vexing distribution of unstressed do, and the fact that Ellipsis can interact with other aspects of the analysis to produce the feeding and blocking relations that are needed to generate the complex facts of EAS. The present approach, superior both descriptively and theoretically to existing transformational approaches, also serves to undermine views of the biology of language and acquisition such as Berwick et al. (2011), which are centered on mappings that manipulate hierarchical phrase structures in a structure-dependent fashion.
In the current study, phage-exposed mimotopes as targets against tegumentary leishmaniasis (TL) were selected by means of bio-panning cycles employing sera of TL patients and healthy subjects, besides the immune stimulation of peripheral blood mononuclear cells (PBMCs) collected from untreated and treated TL patients and healthy subjects. The clones were evaluated regarding their specific interferon-γ (IFN-γ) and interleukin-4 (IL-4) production in the in vitro cultures, and selectivity and specificity values were calculated, and those presenting the best results were selected for the in vivo experiments. Two clones, namely A4 and A8, were identified and used in immunization protocols from BALB/c mice to protect against Leishmania amazonensis infection. Results showed a polarized Th1 response generated after vaccination, being based on significantly higher levels of IFN-γ, IL-2, IL-12, tumour necrosis factor-α (TNF-α) and granulocyte-macrophage colony-stimulating factor (GM-CSF); which were associated with lower production of specific IL-4, IL-10 and immunoglobulin G1 (IgG1) antibodies. Vaccinated mice presented significant reductions in the parasite load in the infected tissue and distinct organs, when compared with controls. In conclusion, we presented a strategy to identify new mimotopes able to induce Th1 response in PBMCs from TL patients and healthy subjects, and that were successfully used to protect against L. amazonensis infection.
Recent open-label trials show that psychedelics, such as ayahuasca, hold promise as fast-onset antidepressants in treatment-resistant depression.
To test the antidepressant effects of ayahuasca, we conducted a parallel-arm, double-blind randomized placebo-controlled trial in 29 patients with treatment-resistant depression. Patients received a single dose of either ayahuasca or placebo. We assessed changes in depression severity with the Montgomery-Åsberg Depression Rating Scale (MADRS) and the Hamilton Depression Rating scale at baseline, and at 1 (D1), 2 (D2), and 7 (D7) days after dosing.
We observed significant antidepressant effects of ayahuasca when compared with placebo at all-time points. MADRS scores were significantly lower in the ayahuasca group compared with placebo at D1 and D2 (p = 0.04), and at D7 (p < 0.0001). Between-group effect sizes increased from D1 to D7 (D1: Cohen's d = 0.84; D2: Cohen's d = 0.84; D7: Cohen's d = 1.49). Response rates were high for both groups at D1 and D2, and significantly higher in the ayahuasca group at D7 (64% v. 27%; p = 0.04). Remission rate showed a trend toward significance at D7 (36% v. 7%, p = 0.054).
To our knowledge, this is the first controlled trial to test a psychedelic substance in treatment-resistant depression. Overall, this study brings new evidence supporting the safety and therapeutic value of ayahuasca, dosed within an appropriate setting, to help treat depression. This study is registered at http://clinicaltrials.gov (NCT02914769).
Spectral densities of plasma fluctuations are calculated for the thermal case using classical molecular dynamics (MD) assuming Coulomb interactions and a short-range cutoff radius. The aim of the calculation is to verify limits and performances of such calculations in the light of possible generalizations, e.g. collisional or non-ideal plasmas. Results are presented for ideal, collisionless, fully ionized thermal plasmas. Comparison with the analytical theory reveals a generally satisfactory agreement with possibility for improvement when more strict numerical parameters are used albeit with a strong increase in computational cost. The largest deviations have been observed in the vicinity of the weakly damped eigenmodes. The agreement is strong in other parts of the spectrum, where Landau damping is prominent, and overcomes the effects stemming from the excess collisionality and coupling as well as from the exclusion of short-range collisions.
Goats have played a key role as source of nourishment for humans in their expansion all over the world in long land and sea trips. This has guaranteed a place for this species in the important and rapid episode of livestock expansion triggered by Columbus’ arrival in the Americas in the late 1400s. The aims of this study are to provide a comprehensive perspective on genetic diversity in American goat populations and to assess their origins and evolutionary trajectories. This was achieved by combining data from autosomal neutral genetic markers obtained in more than two thousand samples that encompass a wide range of Iberian, African and Creole goat breeds. In general, even though Creole populations differ clearly from each other, they lack a strong geographical pattern of differentiation, such that populations of different admixed ancestry share relatively close locations throughout the large geographical range included in this study. Important Iberian signatures were detected in most Creole populations studied, and many of them, particularly the Cuban Creole, also revealed an important contribution of African breeds. On the other hand, the Brazilian breeds showed a particular genetic structure and were clearly separated from the other Creole populations, with some influence from Cape Verde goats. These results provide a comprehensive characterisation of the present structure of goat genetic diversity, and a dissection of the Iberian and African influences that gave origin to different Creole caprine breeds, disentangling an important part of their evolutionary history. Creole breeds constitute an important reservoir of genetic diversity that justifies the development of appropriate management systems aimed at improving performance without loss of genomic diversity.
Temperature is expected to modulate the responses of organisms to stress. Here, we aimed to assess the influence of temperature on the interaction between parasitism and fungicide contamination. Specifically, using the cladoceran Daphnia as a model system, we explored the isolated and interactive effects of parasite challenge (yeast Metschnikowia bicuspidata) and exposure to fungicides (copper sulphate and tebuconazole) at two temperatures (17 and 20 °C), in a fully factorial design. Confirming a previous study, M. bicuspidata infection and copper exposure caused independent effects on Daphnia life history, whereas infection was permanently suppressed with tebuconazole exposure. Here, we show that higher temperature generally increased the virulence of the parasite, with the hosts developing signs of infection earlier, reproducing less and dying at an earlier age. These effects were consistent across copper concentrations, whereas the joint effects of temperature (which enhanced the difference between non-infected and infected hosts) and the anti-parasitic action of tebuconazole resulted in a more pronounced parasite × tebuconazole interaction at the higher temperature. Thus, besides independently influencing parasite and contaminant effects, the temperature can act as a modulator of interactions between pollution and disease.
Background and Objective Pain is a frequent symptom in Parkinson’s disease (PD), and the therapeutic alternatives are scarce. The goal of this trial was to measure the effects of botulinum toxin type A (BTXA) in the treatment of limb pain in advanced PD. Methods A randomized double-blind crossover versus placebo study of BTXA for limb pain in advanced Parkinson’s disease was conducted. Subjects received individualized BTXA/placebo dosing per pain distribution in limbs. The primary outcome was a measure of change in global pain on a numeric rating scale (NRS) at 4 and 12 weeks postinjection and on a visual analogue scale 12 weeks after treatment. Secondary outcomes included the percentage of responders, physician-rated clinical global impressions, MDS–UPDRS and PDQ–39 scores, and adverse events. Results A total of 12 subjects completed the trial. Treatment with BTXA (average dose=241.66 U) produced a significant reduction in NRS score 4 weeks after the injections (–1.75 points, range from –3 to 7, p=0.033). However, there was no significant difference compared to placebo (p=0.70). Participants with dystonic pain showed a greater reduction in NRS score after 4 weeks when treated with BTXA (2.66 points vs. 0.75 for placebo). There were no significant differences for any of the secondary outcomes or significant adverse events. Conclusions Targeted BTXA injections were safe in patients with limb pain and advanced PD; however, the present study failed to show a significant effect when compared to placebo. Further studies may be focused on evaluating the effect of BTXA particularly in dystonic pain.
Echocardiographic screening represents an opportunity for reduction in the global burden of rheumatic heart disease. A focussed single-view screening protocol could allow for the rapid training of healthcare providers and screening of patients.
The aim of this study was to determine the sensitivity and specificity of a focussed single-view hand-held echocardiographic protocol for the diagnosis of rheumatic heart disease in children.
A total of nine readers were divided into three reading groups; each interpreted 200 hand-held echocardiography studies retrospectively as screen-positive, if mitral regurgitation ⩾1.5 cm and/or any aortic insufficiency were observed, or screen-negative from a pooled study library. The performance of experts receiving focussed hand-held protocols, non-experts receiving focussed hand-held protocols, and experts receiving complete hand-held protocols were determined in comparison with consensus interpretations on fully functional echocardiography machines.
In all, 587 studies including 76 on definite rheumatic heart disease, 122 on borderline rheumatic heart disease, and 389 on normal cases were available for analysis. The focussed single-view protocol had a sensitivity of 81.1%, specificity of 75.5%, negative predictive value of 88.5%, and a positive predictive value of 63.2%; expert readers had higher specificity (86.1 versus 64.8%, p<0.01) but equal sensitivity. Sensitivity – experts, 96% and non-experts, 95% – and negative predictive value – experts, 99% and non-experts, 98% – were better for definite rheumatic heart disease. False-positive screening studies resulting from erroneous identification of mitral regurgitation and aortic insufficiency colour jets increased with shortened protocols and less experience (p<0.01).
Our data support a focussed screening protocol limited to parasternal long-axis images. This holds promise in making echocardiographic screening more practical in regions where rheumatic heart disease remains endemic.
The GALILEO telescope requires a flexible detector controller that allows one to drive single and mosaic CCDs in different modes of operation. The CCD controller can be divided into two main parts: the preamplifier, located close to the cryostat and the other modules, the Sequencer, the Bias generator, the Clock driver, the Preamplifier and the Correlated double sampler, located into a rack and connected together via a CCDC-BUS.
Zinc oxide/silicon nanowires (ZnO/SiNWs) nanocomposites is a promising material for heterojunction solar cells. They combine the low-reflectivity of SiNWs, where photogenerated charge carriers are produced and harvested, and the high transparency of ZnO, which serves as a functional transparent conductive electrode. In this paper, we present a study of the anti-reflective properties of ZnO/SiNWs core-shell nanostructures. SiNWs were fabricated by a two-step metal-assisted chemical etching and coated with ZnO by electrochemical deposition. Particularly, the change in the specular reflectance of ZnO/SiNWs nanocomposites as a function of thermal annealing temperature under ambient atmosphere is investigated. First, it was shown that the reflectance in the wavelength range of 400-1000 nm of as-synthesized ZnO/SiNWs nanocomposites increases when compared to the bare SiNWs formed from Si wafers with resistivity of 0.3 and 12 Ω∙cm by an 0.51 % and 0.47 %, respectively. Second, it was found that annealed ZnO/SiNWs had a 0.26 % and 0.17 % lower reflectance in the wavelength range of 400-1000 nm than as-synthesized ZnO/SiNWs and yet higher than bare SiNWs. Potential causes such results are discussed in the context of existing literature.
Copper-alumina and copper-silica aerogels formed by impregnation of a copper(II) salt into an alumina or silica wet gel before supercritical extraction have been found to contain copper in multiple oxidation states: Cu0, Cu+1 and Cu+2. These aerogels are effective at catalyzing the reduction of NO and the oxidation of HCs and CO under conditions similar to those found in automotive three way catalysts. In this work we have developed a preparation method incorporating Cu0, Cu+1 and Cu+2 nanoparticles directly into silica aerogels. Nanoparticles in the form of (a) Cu0 nanorods (100 nm diameter, 10-20 μm length); (b) Cu+1 nanoparticles (350 nm diameter); and (c) Cu+2 nanoparticles (25-55 nm diameter) were added (0.5-15% by weight) to separate precursor mixtures consisting of tetramethyl orthosilicate, methanol, water and ammonia. These precursor mixtures were then processed using a rapid supercritical extraction (RSCE) method to form aerogels. The resulting aerogels show evidence of nanoparticles dispersed throughout the silica aerogel structure. Addition of Cu+1 and Cu+2 nanoparticles decreases the surface area of the aerogels significantly. X-Ray diffraction shows that regardless of initial oxidation state of the nanoparticles, crystalline Cu0 is detected after RSCE processing to 290 °C. Following heat treatment at 700 °C, crystalline Cu+2 is detected. The copper containing silica aerogels are found to be catalytically active with light-off temperatures (50% conversion) for NO and CO at 400 °C in three-way catalytic applications.
Stellar occultations by solar system objects allow kilometric accuracy, permit the detection of tenuous atmospheres (at nbar level), and the discovery of rings. The main limitation was the prediction accuracy, typically 40 mas, corresponding to about 1,000 km projected at the body. This lead to large time dedicated to astrometry, tedious logistical issues, and more often than not, mere miss of the event. The Gaia catalog, with sub-mas accuracy, hugely improves both the star positions, resulting in achievable accuracies of about 1 mas for the shadow track on Earth. This permits much more carefully planned campaigns, with success rate approaching 100%, weather permitting. Scientific perspectives are presented, e.g. central flashes caused by Plutos atmosphere revealing hazes and winds near its surface, grazing occultations showing topographic features, occultations by Chariklos rings unveiling dynamical features such as proper mode “breathing”.
Stellar occultations are a unique technique to access physical characteristics of distant solar system objects from the ground. They allow the measure of the size and the shape at kilometric level, the detection of tenuous atmospheres (few nanobars), and the investigation of close vicinity (satellites, rings) of Transneptunian objects and Centaurs. This technique is made successful thanks to accurate predictions of occultations. Accuracy of the predictions depends on the uncertainty in the position of the occulted star and the object's orbit. The Gaia stellar catalogue (Gaia Collaboration (2017)) now allows to get accurate astrometric stellar positions (to the mas level). The main uncertainty remains on the orbit. In this context, we now take advantage of the NIMA method (Desmars et al.(2015)) for the orbit determination and of the Gaia DR1 catalogue for the astrometry. In this document, we show how the orbit determination is improved by reducing current and some past observations with Gaia DR1. Moreover, we also use more than 45 past positive occultations observed in the 2009-2017 period to derive very accurate astrometric positions only depending on the position of the occulted stars (about few mas with Gaia DR1). We use the case of (10199) Chariklo as an illustration. The main limitation lies in the imprecision of the proper motions which is going to be solved by the Gaia DR2 release.
Parents are a major supplier of alcohol to adolescents, yet there is limited research examining the impact of this on adolescent alcohol use. This study investigates associations between parental supply of alcohol, supply from other sources, and adolescent drinking, adjusting for child, parent, family and peer variables.
A cohort of 1927 adolescents was surveyed annually from 2010 to 2014. Measures include: consumption of whole drinks; binge drinking (>4 standard drinks on any occasion); parental supply of alcohol; supply from other sources; child, parent, family and peer covariates.
After adjustment, adolescents supplied alcohol by parents had higher odds of drinking whole beverages [odds ratio (OR) 1.80, 95% confidence interval (CI) 1.33–2.45] than those not supplied by parents. However, parental supply was not associated with bingeing, and those supplied alcohol by parents typically consumed fewer drinks per occasion (incidence rate ratio 0.86, 95% CI 0.77–0.96) than adolescents supplied only from other sources. Adolescents obtaining alcohol from non-parental sources had increased odds of drinking whole beverages (OR 2.53, 95% CI 1.86–3.45) and bingeing (OR 3.51, 95% CI 2.53–4.87).
Parental supply of alcohol to adolescents was associated with increased risk of drinking, but not bingeing. These parentally-supplied children also consumed fewer drinks on a typical drinking occasion. Adolescents supplied alcohol from non-parental sources had greater odds of drinking and bingeing. Further follow-up is necessary to determine whether these patterns continue, and to examine alcohol-related harm trajectories. Parents should be advised that supply of alcohol may increase children's drinking.
In this review, the available evidence to guide clinicians regarding eligibility for deep brain stimulation (DBS) in the main conditions in which these forms of therapy are generally indicated—Parkinson’s disease (PD), tremor, and dystonia—is presented. In general, the literature shows that DBS is effective for PD, essential tremor, and idiopathic dystonia. In these cases, key points in patient selection must include the level of disability and inability to manage symptoms using the best available medical therapy. Results are, however, still not optimal when dealing with other aetiologies, such as secondary tremors and symptomatic dystonia. Also, in PD, issues such as age and neuropsychiatric profile are still debatable parameters. Overall, currently available literature is able to guide physicians on basic aspects of patient selection and indications for DBS; however, a few points are still debatable and controversial. These issues should be refined and clarified in future studies.
Synthesis and structural characterization of a novel palladium Pd(II) complex with the amino acid L-citrulline (Cit, C6H13N3O3) are presented in this paper. Elemental analysis indicates a 1:2 metal/ligand molar composition for the complex, with the molecular formula PdC12H24N6O6. The compound was also characterized by infrared (IR) spectroscopic measurements and the crystal structure has been solved by powder X-ray diffraction data with simulated annealing strategy in real space. The Pd(II) complex crystallizes in the triclinic system with space group P-1 and cell parameters a = 4.6493(4) Å, b = 5.222(4) Å, c = 18.040(2) Å, α = 77.41(6)°, β = 94.72(7),° and γ = 101.45(7)°. The crystal structure confirms the presence of Pd(II) ions in a nearly square planar environment and the molecular formula with deprotonated citrulline as proposed by analytical and spectroscopic data.