Second-generation nitazoxanide derivatives: thiazolides are effective inhibitors of the influenza A virus

Aim: The only small molecule drugs currently available for treatment of influenza A virus (IAV) are M2 ion channel blockers and sialidase inhibitors. The prototype thiazolide, nitazoxanide, has successfully completed Phase III clinical trials against acute uncomplicated influenza. Results: We report the activity of seventeen thiazolide analogs against A/PuertoRico/8/1934(H1N1), a laboratory-adapted strain of the H1N1 subtype of IAV, in a cell culture-based assay. A total of eight analogs showed IC50s in the range of 0.14–5.0 μM. Additionally a quantitative structure–property relationship study showed high correlation between experimental and predicted activity based on a molecular descriptor set. Conclusion: A range of thiazolides show useful activity against an H1N1 strain of IAV. Further evaluation of these molecules as potential new small molecule therapies is justified

Increased insolation threshold for runaway greenhouse processes on Earth like planets

Because the solar luminosity increases over geological timescales, Earth climate is expected to warm, increasing water evaporation which, in turn, enhances the atmospheric greenhouse effect. Above a certain critical insolation, this destabilizing greenhouse feedback can "runaway" until all the oceans are evaporated. Through increases in stratospheric humidity, warming may also cause oceans to escape to space before the runaway greenhouse occurs. The critical insolation thresholds for these processes, however, remain uncertain because they have so far been evaluated with unidimensional models that cannot account for the dynamical and cloud feedback effects that are key stabilizing features of Earth's climate. Here we use a 3D global climate model to show that the threshold for the runaway greenhouse is about 375 W/m$^2$, significantly higher than previously thought. Our model is specifically developed to quantify the climate response of Earth-like planets to increased insolation in hot and extremely moist atmospheres. In contrast with previous studies, we find that clouds have a destabilizing feedback on the long term warming. However, subsident, unsaturated regions created by the Hadley circulation have a stabilizing effect that is strong enough to defer the runaway greenhouse limit to higher insolation than inferred from 1D models. Furthermore, because of wavelength-dependent radiative effects, the stratosphere remains cold and dry enough to hamper atmospheric water escape, even at large fluxes. This has strong implications for Venus early water history and extends the size of the habitable zone around other stars.Comment: Published in Nature. Online publication date: December 12, 2013. Accepted version before journal editing and with Supplementary Informatio

The effect of total arterial grafting on medium-term outcomes following coronary artery bypass grafting

<p>Abstract</p> <p>Background</p> <p>While it is believed that total arterial grafting (TAG) for coronary artery bypass grafting (CABG) confers improved long-term outcomes when compared to conventional grafting with left internal mammary artery and saphenous vein grafts (LIMA+SVG), to date, this has not become the standard of care. In this study, we assessed the impact of TAG on medium-term outcomes after CABG.</p> <p>Methods</p> <p>Peri-operative data was prospectively collected on consecutive first-time, isolated CABG patients between 1995 and 2005. Patients were divided into two groups based on grafting strategy: TAG (all arterial grafts no saphenous veins) or LIMA+SVG. Patients who had an emergent status or underwent fewer than two distal bypasses were excluded. Medium term univariate and risk-adjusted comparisons between TAG and LIMA+SVG cases were performed.</p> <p>Results</p> <p>A total of 4696 CABG patients were included with 1019 patients undergoing TAG (22%). Unadjusted in-hospital mortality was 1.5% for TAG patients compared to 2.0% for LIMA+SVG (p = 0.31). The mean follow-up was 4.8 ± 2.0 years for TAG patients compared to 6.1 ± 3.0 years for LIMA+SVG patients (p < 0.0001). At follow-up total mortality (8% vs 19%; p < 0.0001), and the incidence of readmission to hospital for cardiac reasons (29% vs 38%; p < 0.0001) were significantly lower in TAG compared to LIMA+SVG patients. However, after adjusting for clinical covariates, TAG did not emerge as a significant independent predictor of long-term mortality (HR 0.92; CI 0.71–1.18), readmission to hospital (HR 1.02; CI 0.89–1.18) or the composite outcome of mortality and readmission (HR 1.00; CI 0.88–1.15). Risk adjusted survival was better than 88% in both TAG and LIMA-SVG patients at 5 years follow-up.</p> <p>Conclusion</p> <p>Patients undergoing TAG appear to experience lower rates of medium-term all-cause mortality and readmission to hospital for any cardiac cause when compared to patients undergoing LIMA+SVG. However, after adjusting for clinical variables, this difference no longer persists suggesting that at median follow-up there are no mortality or morbidity benefit based on the choice of conduit.</p

The management of bronchus intermedius complications after lung transplantation: A retrospective study

<p>Abstract</p> <p>Background</p> <p>Airway complications following lung transplantation remain a significant cause of morbidity and mortality. The management of bronchial complications in Bronchus Intermedius (BI) is challenging due to the location of right upper bronchus. The aim of this study was to analyze the results of BI Montgomery T-tube stent in a consecutive patients with lung transplantations.</p> <p>Methods</p> <p>Between January 2007 and December 2010, 132 lung transplantations were performed at Foch Hospital, Suresnes, France. All the patients who had BI Montgomery T-tube after lung transplantation were included in this retrospective study. The demographic and interventional data and also complications were recorded.</p> <p>Results</p> <p>Out of 132 lung transplant recipients, 12 patients (9 male and 3 female) were entered into this study. The indications for lung transplantation were: cystic fibrosis 8 (67%), emphysema 3 (25%), and idiopathic pulmonary fibrosis 1 (8%). Most of the patients (83%) had bilateral lung transplantation. The mean interval between lung transplantation and interventional bronchoscopy was 11.5 ± 9.8 (SD) months. There was bronchial stenosis at the level of BI in 7 patients (58.3%). The Montgomery T-tube number 10 was used in 9 patients (75%). There was statistically significant difference in Forced Expiratory Volume in one second (FEV1) before and after stent placement (p = 0.01). The most common complication after stent placement was migration (33%).</p> <p>Conclusion</p> <p>BI complications after lung transplantation are still a significant problem. Stenosis or malacia following lung transplantation could be well managed with modified Montgomery T-tube.</p

Methods to collect Anopheles mosquitoes and evaluate malaria transmission: A comparative study in two villages in Senegal

<p>Abstract</p> <p>Background</p> <p>Various methods have been studied as replacement of human landing catches (HLC) for mosquito sampling in entomological studies on malaria transmission. Conflicting results have been obtained in comparing relative efficiency of alternative methods, according to the area, the species present and their density. The aim of this study was to compare the number and characteristics of mosquitoes sampled in two areas of Senegal by three different methods: HLC, light traps adjacent to an occupied bed net (LT/N), pyrethrum spray catches (PSC).</p> <p>Methods</p> <p>Collections were performed in two villages: Dielmo (Soudan savanna) and Bandafassi (Soudan Guinean savanna), two or three nights per month for a 4-5 months period during the maximal transmission season in 2001-2002. Species were identified and <it>Plasmodium </it>infection determined by ELISA. The specific composition, circumsporozoite protein rate and entomological inoculation rate were calculated.</p> <p>Results</p> <p>The diversity of mosquito species captured was maximal with LT/N, minimal with PSC. The mean number of anopheles captures each night was significantly different according to the method used and the species. PSC displayed a significantly lower anopheles density. HLC was the most efficient sampling method when <it>Anopheles gambiae </it>was the main vector (in Bandafassi); LT/N when it was <it>Anopheles funestus </it>(in Dielmo). A significant correlation was found between HLC and LT/M but correlation parameters were different according to the species. Circumsporozoite protein rates were not significantly different between methods or species. The entomological inoculation rate varied along with vector density and thus with methods and species.</p> <p>Conclusions</p> <p>The choice of sampling method influenced entomological data recorded. Therefore, the sampling technique has to be chosen according to the vector studied and the aim of the study. Only HLC must be considered as the reference method, but in some conditions LT/N can be used as an alternative method.</p

A rocky planet transiting a nearby low-mass star

M-dwarf stars -- hydrogen-burning stars that are smaller than 60 per cent of the size of the Sun -- are the most common class of star in our Galaxy and outnumber Sun-like stars by a ratio of 12:1. Recent results have shown that M dwarfs host Earth-sized planets in great numbers: the average number of M-dwarf planets that are between 0.5 to 1.5 times the size of Earth is at least 1.4 per star. The nearest such planets known to transit their star are 39 parsecs away, too distant for detailed follow-up observations to measure the planetary masses or to study their atmospheres. Here we report observations of GJ 1132b, a planet with a size of 1.2 Earth radii that is transiting a small star 12 parsecs away. Our Doppler mass measurement of GJ 1132b yields a density consistent with an Earth-like bulk composition, similar to the compositions of the six known exoplanets with masses less than six times that of the Earth and precisely measured densities. Receiving 19 times more stellar radiation than the Earth, the planet is too hot to be habitable but is cool enough to support a substantial atmosphere, one that has probably been considerably depleted of hydrogen. Because the host star is nearby and only 21 per cent the radius of the Sun, existing and upcoming telescopes will be able to observe the composition and dynamics of the planetary atmosphere.Comment: Published in Nature on 12 November 2015, available at http://dx.doi.org/10.1038/nature15762. This is the authors' version of the manuscrip