Antiplasmodial activity of a series of 1,3,5-triazine-substituted polyamines

Polyamine biosynthesis and function has been shown to be a good drug target in some parasitic protozoa and it is proposed that the pathway might also represent a target in the malaria parasite Plasmodium falciparum. A series of 1,3,5-triazine-substituted polyamine analogues were tested for activity against Plasmodium falciparum in vitro. The series showed activity against the parasites and were generally more active against the chloroquine-resistant line K1 than the chloroquine-susceptible line NF54. Simple unbranched analogues had better activity than analogues carrying branched or cyclic central chains. Addition of multiple triazine units in general led to increased activity of the compound

Generation of 0.6 J pulses of 16 fs duration through high-repetition rate amplification of self phase modulated pulses

International audienceWe have generated optical pulses of 16fs duration in the submicrojoule range and at a repetition rate of 11 kHz. This was obtained by amplifying self-phase modulated pulses at the output of a fiber, using a couple of dyes to achieve gain covering a large spectrum around 620 n

Effectiveness of a Long-term Home-Based Exercise Training Program in Patients With COPD After Pulmonary Rehabilitation: A Multicenter Randomized Controlled Trial

Background: Most patients with COPD do not maintain exercise training after pulmonary rehabilitation (PR). Research question: Does a 12-month home-based, minimal-equipment strength training program after PR have an effect on dyspnea, exercise capacity, and patient-reported outcomes in patients with COPD? Study design and methods: In a parallel-arm multicenter study across four Swiss PR clinics, patients with COPD were allocated randomly (1:1 ratio) into an intervention group (IG; home-based strength training program) or control group (CG; usual care). The primary outcome was change in Chronic Respiratory Questionnaire (CRQ) dyspnea scale score from baseline to 12 months. Secondary outcomes were change in exercise capacity (1-min sit-to-stand-test [1MSTST], 6-min walk test [6MWT]), health-related quality of life, exacerbations, and symptoms. We assessed the IG's experience by interviews at study end. Main analyses were based on the intention-to-treat approach, and adjusted linear regression models were used. Results: One hundred twenty-three patients with COPD (IG, n = 61; CG, n = 62) were randomized, 61 of whom were women and whose mean ± SD age was 66.8 ± 8.1 years and mean ± SD FEV1 was 39.3 ± 15.3% predicted. One hundred four participants completed 12 months of follow-up (IG, n= 53; CG, n= 51). Of the 53 IG participants, 37 participants (70%) conducted the training until study end. We found no difference in change in CRQ dyspnea scale score over 12 months (adjusted mean difference, 0.28; 95% CI, -0.23 to 0.80; P = .27). We found moderate evidence for a difference in 1MSTST repetitions favoring the IG (adjusted mean difference, 2.6; 95% CI, 0.22-5.03; P = .033), but no evidence for an effect in other outcomes. Seventy-nine percent of the IG reported positive effects that they attributed to the training. Interpretation: The home exercise program had no effect on dyspnea, but improved 1MSTST performance and patient-perceived fitness. The supported program was well accepted by patients with COPD and may facilitate continued exercise training at home. Trial registry: ClinicalTrials.gov; No.: NCT03461887; URL: www. Clinicaltrials: gov. Keywords: COPD; dyspnea; effectiveness; functional exercise capacity; home-based exercise training; long-term maintenance; minimal equipment; pulmonary rehabilitation; quality of life; randomized controlled tria

African Trypanosomes undermine humoral responses and vaccine development : link with inflammatory responses?

African trypanosomosis is a debilitating disease of great medical and socioeconomical importance. It is caused by strictly extracellular protozoan parasites capable of infecting all vertebrate classes including human, livestock, and game animals. To survive within their mammalian host, trypanosomes have evolved efficient immune escape mechanisms and manipulate the entire host immune response, including the humoral response. This report provides an overview of how trypanosomes initially trigger and subsequently undermine the development of an effective host antibody response. Indeed, results available to date obtained in both natural and experimental infection models show that trypanosomes impair homeostatic B-cell lymphopoiesis, B-cell maturation and survival and B-cell memory development. Data on B-cell dysfunctioning in correlation with parasite virulence and trypanosome-mediated inflammation will be discussed, as well as the impact of trypanosomosis on heterologous vaccine efficacy and diagnosis. Therefore, new strategies aiming at enhancing vaccination efficacy could benefit from a combination of (i) early parasite diagnosis, (ii) anti-trypanosome (drugs) treatment, and (iii) anti-inflammatory treatment that collectively might allow B-cell recovery and improve vaccination

Guessing imagined and live chance events: adults behave like children with live events

An established finding is that adults prefer to guess before rather than after a chance event has happened. This is interpreted in terms of aversion to guessing when relatively incompetent: After throwing, the fall could be known. Adults (N=71, mean age 18;11, N=28, mean age 48;0) showed this preference with imagined die-throwing as in the published studies. With live die-throwing, children (N=64, aged 6 and 8 years; N=50, aged 5 and 6 years) and 15-year-olds (N=93, 46) showed the opposite preference, as did 17 adults. Seventeen-year-olds (N=82) were more likely to prefer to guess after throwing with live rather than imagined die-throwing. Reliance on imagined situations in the literature on decision-making under uncertainty ignores the possibility that adults imagine inaccurately how they would really feel: After a real die has been thrown, adults, like children, may feel there is less ambiguity about the outcome

Multi-source analysis reveals latitudinal and altitudinal shifts in range of Ixodes ricinus at its northern distribution limit

<p>Abstract</p> <p>Background</p> <p>There is increasing evidence for a latitudinal and altitudinal shift in the distribution range of <it>Ixodes ricinus</it>. The reported incidence of tick-borne disease in humans is on the rise in many European countries and has raised political concern and attracted media attention. It is disputed which factors are responsible for these trends, though many ascribe shifts in distribution range to climate changes. Any possible climate effect would be most easily noticeable close to the tick's geographical distribution limits. In Norway- being the northern limit of this species in Europe- no documentation of changes in range has been published. The objectives of this study were to describe the distribution of <it>I. ricinus </it>in Norway and to evaluate if any range shifts have occurred relative to historical descriptions.</p> <p>Methods</p> <p>Multiple data sources - such as tick-sighting reports from veterinarians, hunters, and the general public - and surveillance of human and animal tick-borne diseases were compared to describe the present distribution of <it>I. ricinus </it>in Norway. Correlation between data sources and visual comparison of maps revealed spatial consistency. In order to identify the main spatial pattern of tick abundance, a principal component analysis (PCA) was used to obtain a weighted mean of four data sources. The weighted mean explained 67% of the variation of the data sources covering Norway's 430 municipalities and was used to depict the present distribution of <it>I. ricinus</it>. To evaluate if any geographical range shift has occurred in recent decades, the present distribution was compared to historical data from 1943 and 1983.</p> <p>Results</p> <p>Tick-borne disease and/or observations of <it>I. ricinus </it>was reported in municipalities up to an altitude of 583 metres above sea level (MASL) and is now present in coastal municipalities north to approximately 69°N.</p> <p>Conclusion</p> <p><it>I. ricinus </it>is currently found further north and at higher altitudes than described in historical records. The approach used in this study, a multi-source analysis, proved useful to assess alterations in tick distribution.</p

Repositioning of a diaminothiazole series confirmed to target the cyclin-dependent kinase CRK12 for use in the treatment of African animal trypanosomiasis

African animal trypanosomiasis or nagana, caused principally by infection of the protozoan parasites Trypanosoma congolense and Trypanosoma vivax, is a major problem in cattle and other livestocks in sub-Saharan Africa. Current treatments are threatened by the emergence of drug resistance and there is an urgent need for new, effective drugs. Here, we report the repositioning of a compound series initially developed for the treatment of human African trypanosomiasis. A medicinal chemistry program, focused on deriving more soluble analogues, led to development of a lead compound capable of curing cattle infected with both T. congolense and T. vivax via intravenous dosing. Further optimization has the potential to yield a single-dose intramuscular treatment for this disease. Comprehensive mode of action studies revealed that the molecular target of this promising compound and related analogues is the cyclin-dependent kinase CRK12

Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV

The performance of muon reconstruction, identification, and triggering in CMS has been studied using 40 inverse picobarns of data collected in pp collisions at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection criteria covering a wide range of physics analysis needs have been examined. For all considered selections, the efficiency to reconstruct and identify a muon with a transverse momentum pT larger than a few GeV is above 95% over the whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4, while the probability to misidentify a hadron as a muon is well below 1%. The efficiency to trigger on single muons with pT above a few GeV is higher than 90% over the full eta range, and typically substantially better. The overall momentum scale is measured to a precision of 0.2% with muons from Z decays. The transverse momentum resolution varies from 1% to 6% depending on pseudorapidity for muons with pT below 100 GeV and, using cosmic rays, it is shown to be better than 10% in the central region up to pT = 1 TeV. Observed distributions of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO