Pretransplantation Therapy with Hypomethylating Agents in Patients with Myelodysplastic Syndromes Receiving Reduced-Intensity Conditioning Regimens

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Disinfection by-products from halogenation of aqueous solutions of terpenoids

We report the formation of trihalomethanes and other disinfection by-products from four polyfunctional terpenoids during simulated chlorination of natural waters. Complex suites of products were identified by closed loop stripping analysis (CLSA)/gas chromatography-mass spectrometry (GC-MS) from halogenation of b-carotene and retinol. b-Ionone appeared to be a key intermediate in the halogenation of b-carotene and retinol, reacting further under the reaction conditions to produce trans-b-ionone-5,6-epoxide and b-cyclocitral. Halogenation of the four terpenoids also produced trihalomethanes (THMs), most likely through haloform reaction on methyl ketone groups within many of the intermediates. Since halogenation of retinol produced a significant quantity of THMs at a slow reaction rate, retinol-based structures may possibly contribute to the slow reacting phase of THM formation in natural waters. Two polyhydroxyphenol model compounds were halogenated for comparison. The only products identified by CLSA/GC-MS from halogenation of 40,5,7- trihydroxyflavanone and ellagic acid were THMs. 40,5,7-Trihydroxyflavanone rapidly produced THMs, with an extremely high molar yield (94%) at pH 7. Terpenoids of the b-ionone and retinol type should be considered to be significant THM precursors, while 40,5,7-trihydroxyflavanone has been shown to be an extremely significant THM precursor, potentially present within natural organic matter in water treatment processes and distribution system

Denitrification in intrinsic and specific groundwater vulnerability assessment: A review

Several groundwater vulnerability methodologies have been implemented throughout the years to face the increasing worldwide groundwater pollution, ranging from simple rating methodologies to complex numerical, statistical, and hybrid methods. Most of these methods have been used to evaluate groundwater vulnerability to nitrate, which is considered the major groundwater contaminant worldwide. Together with dilution, the degradation of nitrate via denitrification has been acknowledged as a process that can reduce reactive nitrogen mass loading rates in both deep and shallow aquifers. Thus, denitrification should be included in groundwater vulnerability studies and integrated into the various methodologies. This work reviewed the way in which denitrification has been considered within the vulnerability assessment methods and how it could increase the reliability of the overall results. Rating and statistical methods often disregard or indirectly incorpo-rate denitrification, while numerical models make use of kinetic reactions that are able to quantify the spatial and temporal variations of denitrification rates. Nevertheless, the rating methods are still the most utilized, due to their linear structures, especially in watershed studies. More efforts should be paid in future studies to implement, calibrate, and validate user-friendly vulnerability assessment methods that are able to deal with denitrification capacity and rates at large spatial and temporal scales

Insight on the application of graphene to sandy soils to improve water holding capacity

In this study, the changes in relevant hydraulic parameters (namely hydraulic conductivity, total and effective porosity, specific retention, and longitudinal dispersivity) induced by the introduction of graphene in a calcareous sandy soil and a siliciclastic riverine soil were monitored and modelled via leaching column experiments. Constant pressure head tests were used to calculate the hydraulic conductivity of each column, while leaching experiments were run to estimate total porosity and specific retention, and for each treatment three replicates were done. Columns were then run under saturated conditions via a low flow peristaltic pump and monitored for chloride concentrations. CXTFIT 2.0 was employed to inversely model the column experiments and retrieve effective porosity and longitudinal dispersivity. Results highlighted small changes of hydraulic conductivity and porosity, induced by graphene addition for both soils. A marked increase of specific retention values was instead recorded in the amended columns respect to control ones. Chloride breakthrough curves modelling showed that graphene doubled dispersivity in the calcareous sandy soil compared to the control, while it halved dispersivity in the siliciclastic riverine soil with respect to the control. The results highlight that graphene induces positive shift in the capacity of sandy soil to retain porewater but at the same time it also alters solute transport parameters, like dispersivity, suggesting that further studies need to focus on using several exposure concentrations, durations and mode of exposure, and apply simulated field conditions or perform experiments in real field conditions, to understand the fate of unwanted compound in soils amended with graphene

Silk Vascular Grafts with Optimized Mechanical Properties for the Repair and Regeneration of Small Caliber Blood Vessels

As the incidence of cardiovascular diseases has been growing in recent years, the need for small-diameter vascular grafts is increasing. Considering the limited success of synthetic grafts, vascular tissue engineering/repair/regeneration aim to find novel solutions. Silk fibroin (SF) has been widely investigated for the development of vascular grafts, due to its good biocompatibility, tailorable biodegradability, excellent mechanical properties, and minimal inflammatory reactions. In this study, a new generation of three-layered SF vascular scaffolds has been produced and optimized. Four designs of the SILKGraft vascular prosthesis have been developed with the aim of improving kink resistance and mechanical strength, without compromising the compliance with native vessels and the proven biocompatibility. A more compact arrangement of the textile layer allowed for the increase in the mechanical properties along the longitudinal and circumferential directions and the improvement of the compliance value, which approached that reported for the saphenous and umbilical veins. The higher braid density slightly affected the grafts' morphology, increasing surface roughness, but the novel design mimicked the corrugation approach used for synthetic grafts, causing significant improvements in kink resistance

Human cytomegalovirus-specific CD4+ and CD8+ T-cell reconstitution in adult allogeneic hematopoietic stem cell transplant recipients and immune control of viral infection

Background Human cytomegalovirus infection is the most frequent viral complication in patients undergoing hematopoietic stem cell transplantation. We investigated the development of human cytomegalovirus-specific T cells in adult recipients of hematopoietic stem cell transplants. Design and Methods From May 2003 through October 2006 a total of 45 patients were monitored for human cytomegalovirus-specific T-cell reconstitution. Human cytomegalovirus-infected autologous dendritic cells were used as a stimulus to detect interferon-γ-producing human cytomegalovirus-specific CD8+ and CD4+ T cells during the first year after transplantation. Interleukin-2 production by specific T cells was also determined. ![Figure 1.][1] Figure 1. Probability of HCMV infection development and HCMV-specific CD4+ and CD8+ T-cell immunity reconstitution. A: cumulative incidence curves of HCMV infection according to donor (D) and recipient (R) HCMV-serostatus. B: cumulative incidence curves of HCMV infection and HCMV-specific CD8+ and CD4+ T-cell reconstitution (i.e. corresponding to a specific T-cell number greater than 0.4 cells/μL blood). C: cumulative incidence curves of HCMV-specific CD8+ T-cell reconstitution according to D/R HCMV-serostatus. D: cumulative incidence curves of HCMV-specific CD4+ T-cell reconstitution according to D/R HCMV-serostatus. Results Human cytomegalovirus infection was detected in the blood of 39/45 patients at a median of 29 days after transplantation. Human cytomegalovirus-specific T-cell reconstitution followed reactivation of latent human cytomegalovirus infection at a median time of about 2 months after transplantation. Only donor human cytomegalovirus-seronegativity and bone marrow as a stem cell source were found to delay specific T-cell reconstitution significantly. Levels of three CD8+ and one CD4+ human cytomegalovirus-specific T-cells/μL blood had a positive predictive value of around 80% for identifying patients able to control human cytomegalovirus infection spontaneously. Five patients who received high doses of steroids for treatment of graft-versus-host disease developed human cytomegalovirus infection requiring pre-emptive treatment despite high levels of interferon-γ-producing T cells in response to human cytomegalovirus. Specific interleukin-2 production was not detected in patients with human cytomegalovirus infection requiring treatment, while 90% of patients who spontaneously controlled human cytomegalovirus infection had T cells that produced interleukin-2 and interferon-γ. Conclusions Pre-transplant human cytomegalovirus infection of the recipient is a major factor driving human cytomegalovirus-specific immune reconstitution. Control of human cytomegalovirus infection likely requires the presence of both interferon-γ and interleukin-2 producing T cells. Corticosteroid treatment may favor active viral replication even in patients with specific T cells. [1]: pending:ye

In-vivo evaluation of silk fibroin small-diameter vascular grafts: state of art of preclinical studies and animal models

Autologous vein and artery remains the first choice for vascular grafting procedures in small-diameter vessels such as coronary and lower limb districts. Unfortunately, these vessels are often found to be unsuitable in atherosclerotic patients due to the presence of calcifications or to insufficient size. Synthetic grafts composed of materials such as expanded polytetrafluoroethylene (ePTFE) are frequently employed as second choice, because of their widespread availability and success in the reconstruction of larger arteries. However, ePTFE grafts with small diameter are plagued by poor patency rates due to surface thrombogenicity and intimal hyperplasia, caused by the bioinertness of the synthetic material and aggravated by low flow conditions. Several bioresorbable and biodegradable polymers have been developed and tested to exploit such issues for their potential stimulation to endothelialization and cell infiltration. Among these, silk fibroin (SF) has shown promising pre-clinical results as material for small-diameter vascular grafts (SDVGs) because of its favorable mechanical and biological properties. A putative advantage in graft infection in comparison with synthetic materials is plausible, although it remains to be demonstrated. Our literature review will focus on the performance of SF-SDVGs in vivo, as evaluated by studies performing vascular anastomosis and interposition procedures, within small and large animal models and different arterial districts. Efficiency under conditions that more accurately mime the human body will provide encouraging evidence towards future clinical application

Silk Fibroin Vascular Graft: From Design to In Vitro and In Vivo Test

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