Prevalence and progression of chronic kidney disease after a liver transplant: a prospective, real-life, observational, two-year multicenter study

Introduction: chronic kidney disease is a frequent complication after liver transplantation. The use of calcineurin inhibitors is one of the causes of this complication. Current immunsuppression regimens that reduce the use of calcineurin inhibitors may be associated with an improved preservation of renal function. Objective: the study aimed to assess the evolution of renal function after liver transplantation in the current routine clinical practice. Methods: an observational, prospective, multicenter study in adult liver transplant recipients was performed. Two hundred and thirty patients with a good renal function before transplantation were assessed six months post-transplantation (baseline) and every six months until month 30. Results: at baseline, 32% of the patients had a reduction in the glomerular filtration rate below < 60 ml/min/1.73 m2. The mean glomerular filtration rate increased from 72.3 to 75.6 ml/min/1.73 m2 at baseline and month 30 respectively (p < 0.01). The mean serum creatinine levels (mg/dl) decreased from 1.13 to 1.09 (p < 0.01). The percentage of patients with stage 3 chronic kidney disease decreased from 31.7% to 26.4%, whereas the percentage of patients with stage 4 remained unchanged (0.4% at baseline and 0.5% at month 30). No patients progressed to end-stage kidney disease that required dialysis or renal transplantation. Conclusion: in the routine clinical practice, a moderate deterioration of renal function is frequent after liver transplantation. However, advanced chronic kidney disease is infrequent in patients with a good pre-transplant renal function

Effectiveness of an mHealth intervention combining a smartphone app and smart band on body composition in an overweight and obese population: Randomized controlled trial (EVIDENT 3 study)

Background: Mobile health (mHealth) is currently among the supporting elements that may contribute to an improvement in health markers by helping people adopt healthier lifestyles. mHealth interventions have been widely reported to achieve greater weight loss than other approaches, but their effect on body composition remains unclear. Objective: This study aimed to assess the short-term (3 months) effectiveness of a mobile app and a smart band for losing weight and changing body composition in sedentary Spanish adults who are overweight or obese. Methods: A randomized controlled, multicenter clinical trial was conducted involving the participation of 440 subjects from primary care centers, with 231 subjects in the intervention group (IG; counselling with smartphone app and smart band) and 209 in the control group (CG; counselling only). Both groups were counselled about healthy diet and physical activity. For the 3-month intervention period, the IG was trained to use a smartphone app that involved self-monitoring and tailored feedback, as well as a smart band that recorded daily physical activity (Mi Band 2, Xiaomi). Body composition was measured using the InBody 230 bioimpedance device (InBody Co., Ltd), and physical activity was measured using the International Physical Activity Questionnaire. Results: The mHealth intervention produced a greater loss of body weight (–1.97 kg, 95% CI –2.39 to –1.54) relative to standard counselling at 3 months (–1.13 kg, 95% CI –1.56 to –0.69). Comparing groups, the IG achieved a weight loss of 0.84 kg more than the CG at 3 months. The IG showed a decrease in body fat mass (BFM; –1.84 kg, 95% CI –2.48 to –1.20), percentage of body fat (PBF; –1.22%, 95% CI –1.82% to 0.62%), and BMI (–0.77 kg/m2, 95% CI –0.96 to 0.57). No significant changes were observed in any of these parameters in men; among women, there was a significant decrease in BMI in the IG compared with the CG. When subjects were grouped according to baseline BMI, the overweight group experienced a change in BFM of –1.18 kg (95% CI –2.30 to –0.06) and BMI of –0.47 kg/m2 (95% CI –0.80 to –0.13), whereas the obese group only experienced a change in BMI of –0.53 kg/m2 (95% CI –0.86 to –0.19). When the data were analyzed according to physical activity, the moderate-vigorous physical activity group showed significant changes in BFM of –1.03 kg (95% CI –1.74 to –0.33), PBF of –0.76% (95% CI –1.32% to –0.20%), and BMI of –0.5 kg/m2 (95% CI –0.83 to –0.19). Conclusions: The results from this multicenter, randomized controlled clinical trial study show that compared with standard counselling alone, adding a self-reported app and a smart band obtained beneficial results in terms of weight loss and a reduction in BFM and PBF in female subjects with a BMI less than 30 kg/m2 and a moderate-vigorous physical activity level. Nevertheless, further studies are needed to ensure that this profile benefits more than others from this intervention and to investigate modifications of this intervention to achieve a global effect

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time, and attempts to address it require a clear understanding of how ecological communities respond to environmental change across time and space. While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes, vast areas of the tropics remain understudied. In the American tropics, Amazonia stands out as the world's most diverse rainforest and the primary source of Neotropical biodiversity, but it remains among the least known forests in America and is often underrepresented in biodiversity databases. To worsen this situation, human-induced modifications may eliminate pieces of the Amazon's biodiversity puzzle before we can use them to understand how ecological communities are responding. To increase generalization and applicability of biodiversity knowledge, it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple organism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region's vulnerability to environmental change. 15%–18% of the most neglected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lost

A novel pharmacodynamic assay to evaluate the effects of crystallization inhibitors on calcium phosphate crystallization in human plasma

Cardiovascular calcification (CVC) is a progressive complication of chronic kidney disease and a predictor of CV events and mortality. The use of biomarkers to predict CV risk and activities of potential or current treatment drugs in these patients could have a crucial impact on therapeutic approaches. Our aim was to develop a novel assay for measurement of the rate of calcium phosphate crystallization in human plasma and provide a tool to evaluate the effects of crystallization inhibitors. The efficacy of inhibitors was determined by adding inhibitory compounds (polyphosphates, fetuin-A, sodium thiosulfate or citrate) to control samples. The assay was additionally validated for SNF472, an experimental formulation of phytate being developed for the treatment of calciphylaxis and CVC in patients with end-stage renal disease (ESRD) undergoing hemodialysis (HD). The method was repeatable and reproducible. The plasma crystallization rate was reduced up to 80% in a concentration-dependent manner following treatment with inhibitors in vitro, among which SNF472 was the most potent. This method appears beneficial in evaluating and discriminating between inhibitory activities of compounds such as polyphosphates on calcium phosphate crystallization, which present a novel therapeutic approach to treat CVC in ESRD patients

Surface-enhanced Resonance Raman Scattering (serrs) Using Au Nanohole Arrays On Optical Fiber Tips

Circular and bow tie-shaped Au nanoholes arrays were fabricated on gold films deposited on the tips of single-mode optical fibers. The nanostructures were milled using focused ion beam with a high quality control of their shapes and sizes. The optical fiber devices were used for surface-enhanced resonance Raman scattering (SERRS) measurements in both back- and forward-scattering geometries, yielding promising performance in both detection arrangements. The effect of the hole shape on the SERRS performance was explored with the bow tie nanostructures presenting a better SERRS performance than the circular holes arrays. The results present here are another step towards the development of optical fiber tips modified with plasmonic nanostructures for SERRS applications. [Figure not available: see fulltext.] © 2013 Springer Science+Business Media New York.8211131121Wolfbeis, O.S., (2006) Anal Chem, 78, p. 3859Bello, J.M., Narayanan, V.A., Stokes, D.L., Vodinh, T., (1990) Anal Chem, 62, p. 2437Mullen, K.I., Carron, K.T., (1991) Anal Chem, 63, p. 2196Fleischmann, M., Hendra, P.J., McQuillan, A.J., (1974) Chem Phys Lett, 26, p. 163Jeanmaire, D.L., Vanduyne, R.P., (1977) J Electroanal Chem, 84, p. 1Albrecht, M.G., Creighton, J.A., (1977) J Am Chem Soc, 99, p. 5215Brolo, A.G., Irish, D.E., Smith, B.D., (1997) J Mol Struct, 405, p. 29Wu, D.Y., Li, J.F., Ren, B., Tian, Z.Q., (2008) Chem Soc Rev, 37, p. 1025Kneipp, J., Kneipp, H., Kneipp, K., (2008) Chem Soc Rev, 37, p. 1052Leger, C., Bertrand, P., (2008) Chem Rev, 108, p. 2379Han, X.X., Chen, L., Ji, W., Xie, Y., Zhao, B., Ozaki, Y., (2011) Small, 7, p. 316Pallaoro, A., Braun, G.B., Reich, N.O., Moskovits, M., (2010) Small, 6, p. 618Kneipp, K., Wang, Y., Kneipp, H., Perelman, L.T., Itzkan, I., Dasari, R., Feld, M.S., (1997) Phys Rev Lett, 78, p. 1667Nie, S.M., Emery, S.R., (1997) Science, 275, p. 1102Hudson, S.D., Chumanov, G., (2009) Anal Bioanal Chem, 394, p. 679Bell, S.E.J., Sirimuthu, N.M.S., (2008) Chem Soc Rev, 37, p. 1012Fan, M., Andrade, G.F.S., Brolo, A.G., (2011) Anal Chim Acta, 693, p. 7Aroca, R., (2006) Surface-Enhanced Vibrational Spectroscopy, , New York: WileyLe Ru, E.C., Etchegoin, P.G., (2009) Principles of Surface-Enhanced Raman Spectroscopy: And Related Plasmonic Effects, , Amsterdam: ElsevierKelly, K.L., Coronado, E., Zhao, L.L., Schatz, G.C., (2003) J Phys Chem B, 107, p. 668Brolo, A.G., Sanderson, A.C., (2004) Can J Chem-Revue Canadienne De Chimie, 82, p. 1474Brolo, A.G., Addison, C.J., (2005) J Raman Spectrosc, 36, p. 629Vo-Dinh, T., Stokes, D.L., (2002) Handbook of Vibrational Spectroscopy, p. 1302. , J. M. Chalmers and P. R. Griffiths (Eds.), Chichester: WileyStoddart, P.R., White, D.J., (2009) Anal Bioanal Chem, 394, p. 1761Homola, J., Yee, S.S., Gauglitz, G., (1999) Sensors Actuators B-Chem, 54, p. 3Sharma, A.K., Jha, R., Gupta, B.D., (2007) IEEE Sensors J, 7, p. 1118Guieu, V., Lagugne-Labarthet, F., Servant, L., Talaga, D., Sojic, N., (2008) Small, 4, p. 96Andrade, G.F.S., Brolo, A.G., (2012) Nanoplasmonic Sensors, p. 289. , A. Dmitriev (Ed.), New York: SpringerStokes, D.L., Vo-Dinh, T., (2000) Sensors Actuators B-Chem, 69, p. 28Andrade, G.F.S., Fan, M., Brolo, A.G., (2010) Biosens Bioelectron, 25, p. 2270Zheng, X.L., Guo, D.W., Shao, Y.L., Jia, S.J., Xu, S.P., Zhao, B., Xu, W.Q., Lombardi, J.R., (2008) Langmuir, 24, p. 4394Kostovski, G., White, D.J., Mitchell, A., Austin, M.W., Stoddart, P.R., (2009) Biosens Bioelectron, 24, p. 1531Smythe, E.J., Dickey, M.D., Bao, J., Whitesides, G.M., Capasso, F., (2009) Nano Lett, 9, p. 1132Brolo, A.G., Gordon, R., Leathem, B., Kavanagh, K.L., (2004) Langmuir, 20, p. 4813Brolo, A.G., Arctander, E., Gordon, R., Leathem, B., Kavanagh, K.L., (2004) Nano Lett, 4, p. 2015Gordon, R., Sinton, D., Kavanagh, K.L., Brolo, A.G., (2008) Acc Chem Res, 41, p. 1049Lesuffleur, A., Kumar, L.K.S., Brolo, A.G., Kavanagh, K.L., Gordon, R., (2007) J Phys Chem C, 111, p. 2347Min, Q., Santos, M.J.L., Girotto, E.M., Brolo, A.G., Gordon, R., (2008) J Phys Chem C, 112, p. 15098Dhawan, A., Muth, J.F., Leonard, D.N., Gerhold, M.D., Gleeson, J., Vo-Dinh, T., Russell, P.E., (2008) J Vac Sci Technol B, 26, p. 2168Kovacs, G.J., Loutfy, R.O., Vincett, P.S., Jennings, C., Aroca, R., (1986) Langmuir, 2, p. 689Reilly, T.H., Chang, S.H., Corbman, J.D., Schatz, G.C., Rowlen, K.L., (2007) J Phys Chem C, 111, p. 1689Tarcha, P.J., DeSaja-Gonzalez, J., Rodriguez-Llorente, S., Aroca, R., (1999) Appl Spectrosc, 53, p. 43Pristinski, D., Du, H., (2006) Opt Lett, 31, p. 324

A Novel Ex Vivo Model of Aortic Valve Calcification. A Preliminary Report

[eng] Background: No pharmacological treatment exists to prevent or stop the calcification process of aortic valves causing aortic stenosis. The aim of this study was to develop a robust model of induced calcification in whole aortic valve leaflets which could be suitable for studies of the basic mechanisms and for testing potentially inhibitory drugs. Methods: Pig hearts were obtained from a commercial abattoir. The aortic valve leaflets were dissected free and randomized between experimental groups. Whole leaflets were cultured in individual wells. Two growth media were used for cultivation: standard growth medium and an antimyofibroblastic growth medium. The latter was employed to inhibit contraction of the leaflet into a ball-like structure. Calcification was induced in the growth medium by supplementation with an osteogenic medium. Leaflets were cultivated for four weeks and medium was changed every third day. To block calcification, the inhibitor SNF472 (a formulation of the hexasodium salt of myo-inositol hexaphosphate hexasodium salt) was used at concentrations between 1 and 100 µM. After cultivation for four weeks the leaflets were snap frozen in liquid nitrogen and kept at −80 °C until blind assessment of the calcium amount in leaflets by inductively coupled plasma optical emission spectroscopy. For statistical analysis, a Kruskal-Wallis test with Dunn's post-test was applied. Results: Osteodifferentiation with calcium accumulation was in principle absent when standard medium was used. However, when the antimyofibroblastic medium was used, a strong calcium accumulation was induced (p = 0.006 compared to controls), and this was blocked in a dose-dependent manner by the calcification inhibitor SNF472 (p = 0.008), with an EC50 of 3.3 µM. Conclusion: A model of experimentally induced calcification in cultured whole leaflets from porcine aortic valves was developed. This model can be useful for studying the basic mechanisms of valve calcification and to test pharmacological approaches to inhibit calcification

A novel assay to measure calcification propensity: from laboratory to humans

[eng] Cardiovascular calcification (CVC) contributes to morbidity and mortality in patients undergoing dialysis. We examined the pharmacodynamic effects of SNF472, a calcification inhibitor, on plasma calcium phosphate crystallization using spectrometric measurements, and its correlations with effects on CVC in rats or humans. Rats (N = 38) injected with vitamin D (days 1-3) to induce CVC were infused with saline or SNF472 (days 1-12). Inhibition of CVC was 50-65% with SNF472 3 mg/kg and ~ 80% with SNF472 10 or 30 mg/kg. SNF472 dose-dependently inhibited calcium phosphate crystallization, which correlated with inhibition of CVC (r = 0.628, P = 0.005). In patients with calciphylaxis (N = 14), infusion of SNF472 (~ 7 mg/kg) during hemodialysis for 12 weeks inhibited calcium phosphate crystallization by nearly 70%. In patients with CVC (N = 274), infusion of SNF472 during hemodialysis for 52 weeks inhibited calcium phosphate crystallization (placebo: 15%; 300 mg: 61%; 600 mg: 75%), which correlated with inhibition of CVC (r = 0.401, P = 0.003). These findings show a direct correlation between inhibition of calcium phosphate crystallization in plasma and inhibition of CVC both in a rat model and in humans, supporting the use of the pharmacodynamic assay in clinical trials as a potentially predictive tool to evaluate the activity of calcification inhibitors

Mechanism of action of SNF472, a novel calcification inhibidor to treat vascular calcification and calciphylaxis.

[eng] Background and Purpose No therapy is approved for vascular calcification or calcific uraemic arteriolopathy (calciphylaxis), which increases mortality and morbidity in patients undergoing dialysis. Deposition of hydroxyapatite (HAP) crystals in arterial walls is the common pathophysiologic mechanism. The mechanism of action of SNF472 to reduce HAP deposition in arterial walls was investigated. Experimental Approach We examined SNF472 binding features (affinity, release kinetics and antagonism type) for HAP crystals in vitro, inhibition of calcification in excised vascular smooth muscle cells from rats and bone parameters in osteoblasts from dogs and rats. Key Results SNF472 bound to HAP with affinity (KD) of 1-10 μM and saturated HAP at 7.6 μM. SNF472 binding was fast (80% within 5 min) and insurmountable. SNF472 inhibited HAP crystal formation from 3.8 μM, with complete inhibition at 30.4 μM. SNF472 chelated free calcium with an EC50 of 539 μM. Chelation of free calcium was imperceptible for SNF472 1-10 μM in physiological calcium concentrations. The lowest concentration tested in vascular smooth muscle cells, 1 μM inhibited calcification by 67%. SNF472 showed no deleterious effects on bone mineralization in dogs or in rat osteoblasts. Conclusion and Implications These experiments show that SNF472 binds to HAP and inhibits further HAP crystallization. The EC50 for chelation of free calcium is 50‐fold greater than a maximally effective SNF472 dose, supporting the selectivity of SNF472 for HAP. These findings indicate that SNF472 may have a future role in the treatment of vascular calcification and calcific uraemic arteriolopathy in patients undergoing dialysis

The T2K experiment

The T2K experiment is a long baseline neutrino oscillation experiment. Its main goal is to measure the last unknown lepton sector mixing angle θ13 by observing νe appearance in a νμ beam. It also aims to make a precision measurement of the known oscillation parameters, and sin22θ23, via νμ disappearance studies. Other goals of the experiment include various neutrino cross-section measurements and sterile neutrino searches. The experiment uses an intense proton beam generated by the J-PARC accelerator in Tokai, Japan, and is composed of a neutrino beamline, a near detector complex (ND280), and a far detector (Super-Kamiokande) located 295 km away from J-PARC. This paper provides a comprehensive review of the instrumentation aspect of the T2K experiment and a summary of the vital information for each subsystem