1,066 research outputs found

    Dispelling the myth that habitual caffeine consumption influences the performance response to acute caffeine supplementation

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    Objective: To investigate the influence of habitual caffeine intake on aerobic exercise performance responses to acute caffeine supplementation. Methods: A double-blind, crossover, counterbalanced study was performed. Forty male endurance-trained cyclists were allocated into tertiles according to their daily caffeine intake: low (58 ± 29 mg.d-1), moderate (143 ± 25 mg.d-1), and high consumers (351 ± 139 mg.d-1). Participants completed three trials in which they performed simulated cycling time-trials in the fastest time possible following ingestion of: caffeine (CAF: 6 mg.kg-1 BM), placebo (PLA), and no supplement (CON). Results: Mixed-model analysis revealed time-trial performance was significantly improved in CAF compared to PLA and CON (29.92±2.18 min vs 30.81±2.67 and 31.14±2.71 min; P = 0.05). Blood lactate and ratings of perceived exertion were not different between trials and tertiles (P>0.05). Conclusion: Performance effects of acute caffeine supplementation during a ~30 min cycling TT performance were not influenced by the level of habitual caffeine consumption

    Fracturing ranked surfaces

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    Discretized landscapes can be mapped onto ranked surfaces, where every element (site or bond) has a unique rank associated with its corresponding relative height. By sequentially allocating these elements according to their ranks and systematically preventing the occupation of bridges, namely elements that, if occupied, would provide global connectivity, we disclose that bridges hide a new tricritical point at an occupation fraction p=pcp=p_{c}, where pcp_{c} is the percolation threshold of random percolation. For any value of pp in the interval pc<p1p_{c}< p \leq 1, our results show that the set of bridges has a fractal dimension dBB1.22d_{BB} \approx 1.22 in two dimensions. In the limit p1p \rightarrow 1, a self-similar fracture is revealed as a singly connected line that divides the system in two domains. We then unveil how several seemingly unrelated physical models tumble into the same universality class and also present results for higher dimensions

    Genetic risk factors for ischaemic stroke and its subtypes (the METASTROKE Collaboration): a meta-analysis of genome-wide association studies

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    &lt;p&gt;Background - Various genome-wide association studies (GWAS) have been done in ischaemic stroke, identifying a few loci associated with the disease, but sample sizes have been 3500 cases or less. We established the METASTROKE collaboration with the aim of validating associations from previous GWAS and identifying novel genetic associations through meta-analysis of GWAS datasets for ischaemic stroke and its subtypes.&lt;/p&gt; &lt;p&gt;Methods - We meta-analysed data from 15 ischaemic stroke cohorts with a total of 12 389 individuals with ischaemic stroke and 62 004 controls, all of European ancestry. For the associations reaching genome-wide significance in METASTROKE, we did a further analysis, conditioning on the lead single nucleotide polymorphism in every associated region. Replication of novel suggestive signals was done in 13 347 cases and 29 083 controls.&lt;/p&gt; &lt;p&gt;Findings - We verified previous associations for cardioembolic stroke near PITX2 (p=2·8×10−16) and ZFHX3 (p=2·28×10−8), and for large-vessel stroke at a 9p21 locus (p=3·32×10−5) and HDAC9 (p=2·03×10−12). Additionally, we verified that all associations were subtype specific. Conditional analysis in the three regions for which the associations reached genome-wide significance (PITX2, ZFHX3, and HDAC9) indicated that all the signal in each region could be attributed to one risk haplotype. We also identified 12 potentially novel loci at p&#60;5×10−6. However, we were unable to replicate any of these novel associations in the replication cohort.&lt;/p&gt; &lt;p&gt;Interpretation - Our results show that, although genetic variants can be detected in patients with ischaemic stroke when compared with controls, all associations we were able to confirm are specific to a stroke subtype. This finding has two implications. First, to maximise success of genetic studies in ischaemic stroke, detailed stroke subtyping is required. Second, different genetic pathophysiological mechanisms seem to be associated with different stroke subtypes.&lt;/p&gt

    Sialic Acid Glycobiology Unveils Trypanosoma cruzi Trypomastigote Membrane Physiology.

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    Trypanosoma cruzi, the flagellate protozoan agent of Chagas disease or American trypanosomiasis, is unable to synthesize sialic acids de novo. Mucins and trans-sialidase (TS) are substrate and enzyme, respectively, of the glycobiological system that scavenges sialic acid from the host in a crucial interplay for T. cruzi life cycle. The acquisition of the sialyl residue allows the parasite to avoid lysis by serum factors and to interact with the host cell. A major drawback to studying the sialylation kinetics and turnover of the trypomastigote glycoconjugates is the difficulty to identify and follow the recently acquired sialyl residues. To tackle this issue, we followed an unnatural sugar approach as bioorthogonal chemical reporters, where the use of azidosialyl residues allowed identifying the acquired sugar. Advanced microscopy techniques, together with biochemical methods, were used to study the trypomastigote membrane from its glycobiological perspective. Main sialyl acceptors were identified as mucins by biochemical procedures and protein markers. Together with determining their shedding and turnover rates, we also report that several membrane proteins, including TS and its substrates, both glycosylphosphatidylinositol-anchored proteins, are separately distributed on parasite surface and contained in different and highly stable membrane microdomains. Notably, labeling for α(1,3)Galactosyl residues only partially colocalize with sialylated mucins, indicating that two species of glycosylated mucins do exist, which are segregated at the parasite surface. Moreover, sialylated mucins were included in lipid-raft-domains, whereas TS molecules are not. The location of the surface-anchored TS resulted too far off as to be capable to sialylate mucins, a role played by the shed TS instead. Phosphatidylinositol-phospholipase-C activity is actually not present in trypomastigotes. Therefore, shedding of TS occurs via microvesicles instead of as a fully soluble form

    Karyotype, Sex Determination, and Meiotic Chromosome Behavior in Two Pholcid (Araneomorphae, Pholcidae) Spiders: Implications for Karyotype Evolution

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    There are 1,111 species of pholcid spiders, of which less than 2% have published karyotypes. Our aim in this study was to determine the karyotypes and sex determination mechanisms of two species of pholcids: Physocyclus mexicanus (Banks, 1898) and Holocnemus pluchei (Scopoli, 1763), and to observe sex chromosome behavior during meiosis. We constructed karyotypes for P. mexicanus and H. pluchei using information from both living and fixed cells. We found that P. mexicanus has a chromosome number of 2n = 15 in males and 2n = 16 in females with X0-XX sex determination, like other members of the genus Physocyclus. H. pluchei has a chromosome number of 2n = 28 in males and 2n = 28 in females with XY-XX sex determination, which is substantially different from its closest relatives. These data contribute to our knowledge of the evolution of this large and geographically ubiquitous family, and are the first evidence of XY-XX sex determination in pholcids

    Discovery of Markers of Exposure Specific to Bites of Lutzomyia longipalpis, the Vector of Leishmania infantum chagasi in Latin America

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    Leishmania parasites are transmitted by the bite of an infected vector sand fly that injects salivary molecules into the host skin during feeding. Certain salivary molecules can produce antibodies and can be used as an indicator of exposure to a vector sand fly and potentially the disease it transmits. Here we identified potential markers of specific exposure to the sand fly Lutzomyia longipalpis, the vector of visceral leishmaniasis in Latin America. Initially, we determined which of the salivary proteins produce antibodies in humans, dogs, and foxes from areas endemic for the disease. To identify potential specific markers of vector exposure, we produced nine different recombinant salivary proteins from Lu. longipalpis and tested for their recognition by individuals exposed to another human-biting sand fly, Lu. intermedia, that transmits cutaneous leishmaniasis and commonly occurs in the same endemic areas as Lu. longipalpis. Two of the nine salivary proteins were recognized only by humans exposed to Lu. longipalpis, suggesting they are immunogenic proteins and may be useful in epidemiological studies. The identification of specific salivary proteins as potential markers of exposure to vector sand flies will increase our understanding of vector–human interaction, bring new insights to vector control, and in some instances act as an indicator for risk of acquiring disease

    Measuring access to medicines: a review of quantitative methods used in household surveys

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    <p>Abstract</p> <p>Background</p> <p>Medicine access is an important goal of medicine policy; however the evaluation of medicine access is a subject under conceptual and methodological development. The aim of this study was to describe quantitative methodologies to measure medicine access on household level, access expressed as paid or unpaid medicine acquisition.</p> <p>Methods</p> <p>Searches were carried out in electronic databases and health institutional sites; within references from retrieved papers and by contacting authors.</p> <p>Results</p> <p>Nine papers were located. The methodologies of the studies presented differences in the recall period, recruitment of subjects and medicine access characterization.</p> <p>Conclusions</p> <p>The standardization of medicine access indicators and the definition of appropriate recall periods are required to evaluate different medicines and access dimensions, improving studies comparison. Besides, specific keywords must be established to allow future literature reviews about this topic.</p
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