Hydrogen inhalation ameliorates ventilator-induced lung injury

Introduction\ud Mechanical ventilation (MV) can provoke oxidative stress and an inflammatory response, and subsequently cause ventilator-induced lung injury (VILI), a major cause of mortality and morbidity of patients in the intensive care unit. Inhaled hydrogen can act as an antioxidant and may be useful as a novel therapeutic gas. We hypothesized that, owing to its antioxidant and anti-inflammatory properties, inhaled hydrogen therapy could ameliorate VILI.\ud \ud Methods\ud VILI was generated in male C57BL6 mice by performing a tracheostomy and placing the mice on a mechanical ventilator (tidal volume of 30 ml/kg without positive end-expiratory pressure, FiO2 0.21). The mice were randomly assigned to treatment groups and subjected to VILI with delivery of either 2% nitrogen or 2% hydrogen in air. Sham animals were given same gas treatments for two hours (n = 8 for each group). The effects of VILI induced by less invasive and longer exposure to MV (tidal volume of 10 ml/kg, 5 hours, FiO2 0.21) were also investigated (n = 6 for each group). Lung injury score, wet/dry ratio, arterial oxygen tension, oxidative injury, and expression of pro-inflammatory mediators and apoptotic genes were assessed at the endpoint of two hours using the high-tidal volume protocol. Gas exchange and apoptosis were assessed at the endpoint of five hours using the low-tidal volume protocol.\ud \ud Results\ud Ventilation (30 ml/kg) with 2% nitrogen in air for 2 hours resulted in deterioration of lung function, increased lung edema, and infiltration of inflammatory cells. In contrast, ventilation with 2% hydrogen in air significantly ameliorated these acute lung injuries. Hydrogen treatment significantly inhibited upregulation of the mRNAs for pro-inflammatory mediators and induced antiapoptotic genes. In the lungs treated with hydrogen, there was less malondialdehyde compared with lungs treated with nitrogen. Similarly, longer exposure to mechanical ventilation within lower tidal volume (10 mg/kg, five hours) caused lung injury including bronchial epithelial apoptosis. Hydrogen improved gas exchange and reduced VILI-induced apoptosis.\ud \ud Conclusions\ud Inhaled hydrogen gas effectively reduced VILI-associated inflammatory responses, at both a local and systemic level, via its antioxidant, anti-inflammatory and antiapoptotic effects

Impact of measured versus estimated glomerular filtration rate-based screening on living kidney donor characteristics:A study of multiple cohorts

Background Most transplant centers in the Netherlands use estimated glomerular filtration rate (eGFR) for evaluation of potential living kidney donors. Whereas eGFR often underestimates GFR, especially in healthy donors, measured GFR (mGFR) allows more precise kidney function assessment, and therefore holds potential to increase the living donor pool. We hypothesized that mGFR-based donor screening leads to acceptance of donors with lower predonation eGFR than eGFR-based screening. Methods In this longitudinal cohort study, we compared eGFR (CKD-EPI) before donation in one center using mGFR-based screening (mGFR-cohort, n = 250) with two centers using eGFR-based screening (eGFR-cohort1, n = 466 and eGFR-cohort2, n = 160). We also compared differences in eGFR at five years after donation. Results Donor age was similar among the cohorts (mean±standard deviation (SD) mGFR-cohort 53 ±10 years, eGFR-cohort1 52±13 years, P = 0.16 vs. mGFR-cohort, and eGFR-cohort2 53±9 years, P = 0.61 vs. mGFR-cohort). Estimated GFR underestimated mGFR by 10±12 mL/ min/1.73m2 (mean±SD), with more underestimation in younger donors. In the overall cohorts, mean±SD pre-donation eGFR was lower in the mGFR-cohort (91±13 mL/min/ 1.73m2) than in eGFR-cohort1 (93±15 mL/min/1.73m2, P<0.05) and eGFR-cohort2 (94±12 mL/min/1.73m2, P<0.05). However, these differences disappeared when focusing on more recent years, which can be explained by acceptance of more older donors with lower predonation eGFR over time in both eGFR-cohorts. Five years post-donation, mean±SD eGFR was similar among the centers (mGFR-cohort 62±12 mL/min/1.73m2, eGFR-cohort1 61±14 mL/min/1.73m2, eGFR-cohort2 62±11 mL/min/1.73m2, P = 0.76 and 0.95 vs. mGFR-cohort respectively). In the mGFR-cohort, 38 (22%) donors were excluded from donation due to insufficient mGFR with mean±SD mGFR of 71±9 mL/min/1.73m2. Conclusions Despite the known underestimation of mGFR by eGFR, we did not show that the routine use of mGFR in donor screening leads to inclusion of donors with a lower pre-donation eGFR. Therefore eGFR-based screening will be sufficient for the majority of the donors. Future studies should investigate whether there is a group (e.g. young donors with insufficient eGFR) that might benefit from confirmatory mGFR testing

Defining eye-fixation sequences across individuals and tasks: the Binocular-Individual Threshold (BIT) algorithm

We propose a new fully automated velocity-based algorithm to identify fixations from eye-movement records of both eyes, with individual-specific thresholds. The algorithm is based on robust minimum determinant covariance estimators (MDC) and control chart procedures, and is conceptually simple and computationally attractive. To determine fixations, it uses velocity thresholds based on the natural within-fixation variability of both eyes. It improves over existing approaches by automatically identifying fixation thresholds that are specific to (a) both eyes, (b) x- and y- directions, (c) tasks, and (d) individuals. We applied the proposed Binocular-Individual Threshold (BIT) algorithm to two large datasets collected on eye-trackers with different sampling frequencies, and compute descriptive statistics of fixations for larger samples of individuals across a variety of tasks, including reading, scene viewing, and search on supermarket shelves. Our analysis shows that there are considerable differences in the characteristics of fixations not only between these tasks, but also between individuals

Quantitative-spatial assessment of soil contamination in S. Francisco de Assis due to mining activity of the Panasqueira mine (Portugal)

Through the years, mining and beneficiation processes produces large amounts of As-rich mine wastes laid up in huge tailings and open-air impoundments (Barroca Grande and Rio tailings) that are the main source of pollution in the surrounding area once they are exposed to the weathering conditions leading to the formation of AMD and consequently to the contamination of the surrounding environments, in particularly soils. In order to investigate the environmental contamination impact on S. Francisco de Assis (village located between the two major impoundments and tailings) agricultural soils, a geochemical survey was undertaken to assess toxic metals associations, related levels and their spatial distribution, and to identify the possible contamination sources. According to the calculated contamination factor, As and Zn have a very high contamination factor giving rise to 65.4 % of samples with a moderate to high pollution degree; 34.6 % have been classified as nil to very low pollution degree. The contamination factor spatial distribution put in evidence the fact that As, Cd, Cu, Pb, and Zn soils contents, downstream Barroca Grande tailing, are increased when compared with the local Bk soils. The mechanical dispersion, due to erosion, is the main contamination source. The chemical extraction demonstrates that the trace metals distribution and accumulation in S. Francisco de Assis soils is related to sulfides, but also to amorphous or poorly crystalline iron oxide phases. The partitioning study allowed understanding the local chemical elements mobility and precipitation processes, giving rise to the contamination dispersion model of the study area. The wind and hydrological factors are responsible for the chemical elements transport mechanisms, the water being the main transporter medium and soils as one of the possible retention media

Insecticide resistance in the sand fly, Phlebotomus papatasi from Khartoum State, Sudan

<p>Abstract</p> <p>Background</p> <p><it>Phlebotomus papatasi </it>the vector of cutaneous leishmaniasis (CL) is the most widely spread sand fly in Sudan. No data has previously been collected on insecticide susceptibility and/or resistance of this vector, and a first study to establish a baseline data is reported here.</p> <p>Methods</p> <p>Sand flies were collected from Surogia village, (Khartoum State), Rahad Game Reserve (eastern Sudan) and White Nile area (Central Sudan) using light traps. Sand flies were reared in the Tropical Medicine Research Institute laboratory. The insecticide susceptibility status of first progeny (F1) of <it>P. papatasi </it>of each population was tested using WHO insecticide kits. Also, <it>P. papatasi </it>specimens from Surogia village and Rahad Game Reserve were assayed for activities of enzyme systems involved in insecticide resistance (acetylcholinesterase (AChE), non-specific carboxylesterases (EST), glutathione-S-transferases (GSTs) and cytochrome p450 monooxygenases (Cyt p450).</p> <p>Results</p> <p>Populations of <it>P. papatasi </it>from White Nile and Rahad Game Reserve were sensitive to dichlorodiphenyltrichloroethane (DDT), permethrin, malathion, and propoxur. However, the <it>P. papatasi </it>population from Surogia village was sensitive to DDT and permethrin but highly resistant to malathion and propoxur. Furthermore, <it>P. papatasi </it>of Surogia village had significantly higher insecticide detoxification enzyme activity than of those of Rahad Game Reserve. The sand fly population in Surogia displayed high AChE activity and only three specimens had elevated levels for EST and GST.</p> <p>Conclusions</p> <p>The study provided evidence for malathion and propoxur resistance in the sand fly population of Surogia village, which probably resulted from anti-malarial control activities carried out in the area during the past 50 years.</p

Restriction of HIV-1 Replication in Monocytes Is Abolished by Vpx of SIVsmmPBj

Background: Human primary monocytes are refractory to infection with the human immunodeficiency virus 1 (HIV-1) or transduction with HIV-1-derived vectors. In contrast, efficient single round transduction of monocytes is mediated by vectors derived from simian immunodeficiency virus of sooty mangabeys (SIVsmmPBj), depending on the presence of the viral accessory protein Vpx. Methods and Findings: Here we analyzed whether Vpx of SIVsmmPBj is sufficient for transduction of primary monocytes by HIV-1-derived vectors. To enable incorporation of PBj Vpx into HIV-1 vector particles, a HA-Vpr/Vpx fusion protein was generated. Supplementation of HIV-1 vector particles with this fusion protein was not sufficient to facilitate transduction of human monocytes. However, monocyte transduction with HIV-1-derived vectors was significantly enhanced after delivery of Vpx proteins by virus-like particles (VLPs) derived from SIVsmmPBj. Moreover, pre-incubation with Vpx-containing VLPs restored replication capacity of infectious HIV-1 in human monocytes. In monocytes of non-human primates, single-round transduction with HIV-1 vectors was enabled. Conclusion: Vpx enhances transduction of primary human and even non-human monocytes with HIV-1-derived vectors, only if delivered in the background of SIVsmmPBj-derived virus-like particles. Thus, for accurate Vpx function the presence of SIVsmmPBj capsid proteins might be required. Vpx is essential to overcome a block of early infection steps in primary monocytes