Shikimate pathway in apicomplexan parasites

No abstract available

Microhabitat competition between Iberian fish species and the endangered Júcar nase (Parachondrostoma arrigonis; Steindachner, 1866)

"This is an Accepted Manuscript of an article published by Taylor & Francis in Journal of Ecohydraulics on 24-01-2017, available online: https://www.tandfonline.com/doi/full/10.1080/24705357.2016.1276417"[EN] Competition with invasive species is recognized as having a major impact on biodiversity conservation. The upper part of the Cabriel River (Eastern Iberian Peninsula) harbours the most important population of the Júcar nase (Parachondrostoma arrigonis; Steindachner, 1866), a fish species in imminent danger of extinction. Currently, this species cohabits with several non-native species, such as the Iberian nase (Pseudochondrostoma polylepis; Steindachner, 1864) and the bermejuela (Achondrostoma arcasii; Steindachner, 1866). The potential habitat competition with these species was studied by analysing the spatial and temporal overlapping of suitable microhabitats. Generalized Additive Mixed Models (GAMMs) were developed to model microhabitat selection and these GAMMs were used to assess the habitat suitability (i.e. probability of presence) under several flows simulated with River2D. The Júcar nase will compete, spatially and temporally, for the few suitable microhabitats with bermejuela and, to a lesser extent, with small Iberian nase; conversely, large Iberian nase was of minor concern, due to increased differences in habitat preferences. This study represents an important assessment of potential competition and, therefore, these results might assist to better define future management practices in the upper part of the Cabriel River.This study was funded by the Spanish Ministry of Economy and Competitiveness through the SCARCE project (Consolider Ingenio 2010 CSD2009 00065); the Universitat Politècnica de València, through the project UPPTE/2012/294 [PAID 06 12]; it was also partially funded by the IMPADAPT project (CGL2013-48424-C2-1-R) with Spanish MINECO (Ministerio de Economía y Competitividad) and FEDER funds. The authors would like to thank the help of the Conselleria de Territori i Vivenda (Generalitat Valenciana) and the Confederación Hidrográfica del Júcar (Spanish government), which provided environmental data to Alfredo Ollero, and the two anonymous reviewers who first suggested the submission of the paper to a regular journal. Finally, we would like to thank TECNOMA S.A. for the development of the hydraulic model.Muñoz Mas, R.; Soares Costa, RM.; Alcaraz-Hernández, JD.; Martinez-Capel, F. (2017). Microhabitat competition between Iberian fish species and the endangered Júcar nase (Parachondrostoma arrigonis; Steindachner, 1866). Journal of Ecohydraulics. 2(1):3-15. https://doi.org/10.1080/24705357.2016.1276417S31521Alcaraz, C., Carmona-Catot, G., Risueño, P., Perea, S., Pérez, C., Doadrio, I., & Aparicio, E. (2014). Assessing population status of Parachondrostoma arrigonis (Steindachner, 1866), threats and conservation perspectives. Environmental Biology of Fishes, 98(1), 443-455. doi:10.1007/s10641-014-0274-3ALMEIDA, D., & GROSSMAN, G. D. (2012). Utility of direct observational methods for assessing competitive interactions between non-native and native freshwater fishes. 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Explosive pulsed power experimental capability at LLNL

Abstract not provide

Expectations, perceptions, and physiotherapy predict prolonged sick leave in subacute low back pain

<p>Abstract</p> <p>Background</p> <p>Brief intervention programs for subacute low back pain (LBP) result in significant reduction of sick leave compared to treatment as usual. Although effective, a substantial proportion of the patients do not return to work. This study investigates predictors of return to work in LBP patients participating in a randomized controlled trial comparing a brief intervention program (BI) with BI and physical exercise.</p> <p>Methods</p> <p>Predictors for not returning to work was examined in 246 patients sick listed 8-12 weeks for low back pain. The patients had participated in a randomized controlled trial, with BI (n = 122) and BI + physical exercise (n = 124). There were no significant differences between the two intervention groups on return to work. The groups were therefore merged in the analyses of predictors. Multiple logistic regression analysis was used to identify predictors for non return to work at 3, 12, and 24 months of follow-up.</p> <p>Results</p> <p>At 3 months of follow-up, the strongest predictors for not returning to work were pain intensity while resting (OR = 5.6; CI = 1.7-19), the perception of constant back strain when working (OR = 4.1; CI = 1.5-12), negative expectations for return to work (OR = 4.2; CI = 1.7-10), and having been to a physiotherapist prior to participation in the trial (OR = 3.3; CI = 1.3-8.3). At 12 months, perceived reduced ability to walk far due to the complaints (OR = 2.6; CI = 1.3-5.4), pain during activities (OR = 2.4; CI = 1.1-5.1), and having been to a physiotherapist prior to participation in the trial (OR = 2.1; CI = 1.1-4.3) were the strongest predictors for non return to work. At 24 months age below 41 years (OR = 2.9; CI = 1.4-6.0) was the only significant predictor for non return to work.</p> <p>Conclusion</p> <p>It appears that return to work is highly dependant on individual and cognitive factors. Patients not returning to work after the interventions were characterized by negative expectations, perceptions about pain and disability, and previous physiotherapy treatment. This is the first study reporting that previous treatment by physiotherapists is a risk factor for long-term sick leave. This has not been reported before and is an interesting finding that deserves more scrutiny.</p

Effects of Point Mutations in Plasmodium falciparum Dihydrofolate Reductase and Dihydropterate Synthase Genes on Clinical Outcomes and In Vitro Susceptibility to Sulfadoxine and Pyrimethamine

Sulfadoxine-pyrimethamine was a common first line drug therapy to treat uncomplicated falciparum malaria, but increasing therapeutic failures associated with the development of significant levels of resistance worldwide has prompted change to alternative treatment regimes in many national malaria control programs. METHODOLOGY AND FINDING: We conducted an in vivo therapeutic efficacy trial of sulfadoxine-pyrimethamine at two locations in the Peruvian Amazon enrolling 99 patients of which, 86 patients completed the protocol specified 28 day follow up. Our objective was to correlate the presence of polymorphisms in P. falciparum dihydrofolate reductase and dihydropteroate synthase to in vitro parasite susceptibility to sulfadoxine and pyrimethamine and to in vivo treatment outcomes. Inhibitory concentration 50 values of isolates increased with numbers of mutations (single [108N], sextuplet [BR/51I/108N/164L and 437G/581G]) and septuplet (BR/51I/108N/164L and 437G/540E/581G) with geometric means of 76 nM (35-166 nM), 582 nM (49-6890- nM) and 4909 (3575-6741 nM) nM for sulfadoxine and 33 nM (22-51 nM), 81 nM (19-345 nM), and 215 nM (176-262 nM) for pyrimethamine. A single mutation present in the isolate obtained at the time of enrollment from either dihydrofolate reductase (164L) or dihydropteroate synthase (540E) predicted treatment failure as well as any other single gene alone or in combination. Patients with the dihydrofolate reductase 164L mutation were 3.6 times as likely to be treatment failures [failures 85.4% (164L) vs 23.7% (I164); relative risk = 3.61; 95% CI: 2.14 - 6.64] while patients with the dihydropteroate synthase 540E were 2.6 times as likely to fail treatment (96.7% (540E) vs 37.5% (K540); relative risk = 2.58; 95% CI: 1.88 - 3.73). Patients with both dihydrofolate reductase 164L and dihydropteroate synthase 540E mutations were 4.1 times as likely to be treatment failures [96.7% vs 23.7%; RR = 4.08; 95% CI: 2.45 - 7.46] compared to patients having both wild forms (I164 and K540).In this part of the Amazon basin, it may be possible to predict treatment failure with sulfadoxine-pyrimethamine equally well by determination of either of the single mutations dihydrofolate reductase 164L or dihydropteroate synthase 540E.ClinicalTrials.gov NCT00951106

Second Generation Steroidal 4-Aminoquinolines Are Potent, Dual-Target Inhibitors of the Botulinum Neurotoxin Serotype A Metalloprotease and P. falciparum Malaria

Significantly more potent second generation 4-amino-7-chloroquinoline (4,7-ACQ) based inhibitors of the botulinum neurotoxin serotype A (BoNT/A) light chain were synthesized. Introducing an amino group at the C(3) position of the cholate component markedly increased potency (IC50 values for such derivatives ranged from 0.81 to 2.27 mu M). Two additional subclasses were prepared: bis(steroidal)-4,7-ACQ derivatives and bis(4,7-ACQ)cholate derivatives; both classes provided inhibitors with nanomolar-range potencies (e.g., the K-i of compound 67 is 0.10 mu M). During BoNT/A challenge using primary neurons, select derivatives protected SNAP-25 by up to 89%. Docking simulations were performed to rationalize the compounds' in vitro potencies. In addition to specific residue contacts, coordination of the enzyme's catalytic zinc and expulsion of the enzyme's catalytic water were a consistent theme. With respect to antimalarial activity, the compounds provided better IC90 activities against chloroquine resistant (CQR) malaria than CQ, and seven compounds were more active than mefloquine against CQR strain W2

Sediment Transport, Instream Flows, and the Small Hydro Project

The impact of three types of diversion on channel shape, sediment transport capacity, and flushing flows are considered. If a small hydro project diverts water without storage of sediment, the principal sediment concern is that the channel shape and substrate may change downstream of the reservoir. The impact of a diversion structure with little storage depends on the details of the structure