Graphene aerogels as efficient adsorbers of water pollutants and their effect of drying methods.

Environmental accidents highlight the need for the development of efficient materials that can be employed to eliminate pollutants including crude oil and its derivatives, as well as toxic organic solvents. In recent years, a wide variety of advanced materials has been investigated to assist in the purification process of environmentally compromised regions, with the principal contestants being graphene-based structures. This study describes the synthesis of graphene aerogels with two methods and determines their efficiency as adsorbents of several water pollutants. The main difference between the two synthesis routes is the use of freeze-drying in the first case, and ambient pressure drying in the latter. Raman spectroscopy, Scanning Electron Microscopy (SEM), X-ray diffraction (XRD), X-ray Photoelectron Spectroscopy (XPS) and contact angle measurements are employed here for the characterisation of the samples. The as-prepared aerogels have been found to act as photocatalysts of aqueous dye solutions like methylene blue and Orange G, while they were also evaluated as adsorbents of organic solvents (acetone, ethanol and methanol), and, oils like pump oil, castor oil, silicone oil, as well. The results presented here show that the freeze-drying approach provides materials with better adsorption efficiency for the most of the examined pollutants, however, the energy and cost-saving advantages of ambient-pressure-drying could offset the adsorption advantages of the former case.

Graphene nanoplatelets and other 2D-materials as protective means against the fading of coloured inks, dyes and paints.

The present work demonstrates the ability of graphene nanoplatelets (GNPs) and other two-dimensional materials (2DMs) like tungsten disulfide (WS2), molybdenum disulfide (MoS2) and hexagonal boron nitride (hBN) to act as protective barriers against the fading of architectural paints and also inks/paints used in art. The results present a new approach for improving the lightfastness of colours of artworks and painted indoor/outdoor wall surfaces taking advantage of the remarkable properties of 2DMs. As shown herein, commercial inks and architectural paints of different colours doped with graphene nanoplatelets (GNPs), graphene oxide (GO), reduced graphene oxide (rGO) and other 2DMs, exhibit a superior resistance to fading under ultraviolet radiation or even under exposure to visible light. A spectroscopic study on these inks and dyes reveals that the peaks which are characteristic of the colour pigments are less affected from aging/fading when the GNPs and the other 2DMs are present. The protection mechanism for the GNPs and the other 2DMs differs. For GNPs, mainly their high surface area which leads to free radicals scavenging (especially hydroxyl radicals), and secondarily their UV absorption, are responsible for their protection effects, while for GO, a transition to rGO structures and consequently to 'smart' paints can be observed after the performed aging routes. In this way, the paint gets improved by time preventing or slowing its own fading and decolorization. For the other 2DMs, the transition-metal dichalcogenides performed better than hBN, even though they all absorb in the UV region. This can be ascribed to the facts that the formers also absorb in the visible, while hBN does not, while most importantly, they can trap reactive oxygen species (ROS) and corrosive gases in their structure as opposed to hBN. By conducting colorimetric measurements, we have discovered that the lifetime of the as-developed 2DM-doped inks and paints can be extended by up to ∼40%.

Preventing colour fading in artworks with graphene veils.

Modern and contemporary art materials are generally prone to irreversible colour changes upon exposure to light and oxidizing agents. Graphene can be produced in thin large sheets, blocks ultraviolet light, and is impermeable to oxygen, moisture and corrosive agents; therefore, it has the potential to be used as a transparent layer for the protection of art objects in museums, during storage and transportation. Here we show that a single-layer or multilayer graphene veil, produced by chemical vapour deposition, can be deposited over artworks to protect them efficiently against colour fading, with a protection factor of up to 70%. We also show that this process is reversible since the graphene protective layer can be removed using a soft rubber eraser without causing any damage to the artwork. We have also explored a complementary contactless graphene-based route for colour protection that is based on the deposition of graphene on picture framing glass for use when the direct application of graphene is not feasible due to surface roughness or artwork fragility. Overall, the present results are a proof of concept of the potential use of graphene as an effective and removable protective advanced material to prevent colour fading in artworks.

Insights from the Greek experience of the use of Blinatumomab in pediatric relapsed and refractory acute lymphoblastic leukemia patients.

Pediatric refractory or relapsed acute lymphoblastic leukemia (ALL) poses unique therapeutic challenges, with novel immunotherapy approaches offering potential cure opportunities. In this frame, the use of Blinatumomab may induce durable remissions, serving as a successful bridge to allogeneic hematopoietic stem cell transplantation (allo-HSCT). Herein, we retrospectively summarize the Greek experience on pediatric relapsed/refractory B-cell precursor ALL patients that were treated with Blinatumomab in a compassionate, off-label setting as an effort to achieve disease clearance and proceed to allo-HSCT. In our cohort of 9 patients, 6/9 (66.7%) responded to Blinatumomab, achieving complete morphological remission (CR) after the 1st cycle, while minimal/measurable residual disease (MRD)-negativity (<10-4) after the 1st cycle was achieved in 2/2 patients (100.0%) with prior CR. A successful bridge to HSCT was feasible in 5/9 patients (55.6%). Median relapse-free survival (RFS) was 3.0 months (range 0.5-21.4 months) and median overall survival (OS) was 8.7 months (range 1.4-47.1 months) for the whole pediatric cohort. There was a trend of prolonged survival among patients who achieved MRD response after the 1st Blinatumomab administration. MRD response (defined as the >=2-log reduction of MRD value before and after Blinatumomab administration), was associated with a median RFS/OS of 7.4/7.6 months, while lack of MRD response was associated with a median RFS/OS of 0.5/3.0 months, respectively. Novel therapeutic maneuvers, in order to overcome disease resistance, i.e. increased usage of Blinatumomab dose (45 µg/m2/day), combination with donor lymphocyte infusions (DLIs), use of other immunotherapy salvage approaches (inotuzumabozogamicin), are herein discussed. Additionally, the optimal number of Blinatumomab cycles, the CD19-negative relapses and lineage switch, are also addressed. Our data although referred to a limited, however refractory or relapsed and heavily pretreated number of patients, strongly suggest that Blinatumomab may well induce sustained remissions and serve as an effective bridge to HSCT. Whether immunotherapy combined with chemotherapy can outweigh the need for subsequent allo-HSCT, if incorporated into frontline high-risk ALL therapy, remains an optimistic issue to be verified in future randomized clinical trials.

ETV6/RUNX1-positive childhood acute lymphoblastic leukemia (ALL): The spectrum of clonal heterogeneity and its impact on prognosis.

The prognostic significance of the ETV6/RUNX1-fusion and of the accompanying aberrations is disputable; whether co-existing sub-clones are responsible for delayed MRD-clearance and thus, moderate outcome, remains to be clarified. We studied, in a paediatric cohort of 119 B-ALLs, the relation between the ETV6/RUNX1 aberration and the co-existing subclones with (a) presenting clinical/biological features, (b) early response to treatment(MRD) and (c) long-term outcome over a 12-year period. Patients were homogeneously treated according to BFM-based-protocols. 27/119 patients (22.7%) were ETV6/RUNX1-positive; 19/27 (70.4%) harbored additional genetic abnormalities while 9/19 (33.3%) presented with clonal heterogeneity. The most common abnormalities were del12p13 (37%), 3-6×21q22 (22.2%), del9p21 (18.5%) and 2-3xETV6/RUNX1 (18.5%). MRDd15-positivity (≥10-3) was detected in 44% of the cohort; the corresponding MRD among patients carrying subclones rises to 88.9%. Common features of all relapses were sub-clonal diversity, FCM-MRDd15-positivity and additional del(9p21) while there were no censored relapses among ETV6/RUNX1-positive patients with sole translocation and absence of additional aberrations, within a median follow-up time of 90 months. In our study, the presence of clonal heterogeneity and impaired FCM-MRD clearance among ETV6/RUNX1-positive patients, ultimately influenced prognosis. Longer follow-up is needed in order to further validate these initial results.

Simultaneous changes in serum HMGB1 and IFN-α levels and in LAIR-1 expression on plasmatoid dendritic cells of patients with juvenile SLE. New therapeutic options?

We investigated the simultaneous changes in serum levels of HMGB1 and IFN-α as well as in LAIR-1 expression on plasmatoid dendritic cells (pDCs) of juvenile systemic lupus erythematosus (jSLE) patients in order to explore their involvement in the disease pathogenesis and their correlation with disease activity and other characteristics. In total, 62 blood samples were studied from 26 jSLE patients (18 girls), aged 8-16 years. Twenty healthy subjects (16 girls) of comparable age were included as healthy controls (HCs). Concentrations of serum HMGB1 and IFN-α were assessed by ELISA and LAIR-1 expression on pDCs by five-color flow cytometry. The disease activity index was assessed by SLEDAI and ECLAM scores. It was found that mean serum levels both of HMGB1 and IFN-α were significantly increased in jSLE patients compared to HCs and in jSLE patients with active disease with or without active nephritis compared to those with inactive disease. Mean serum levels of HMGB1 were positively correlated with levels of IFN-α and both were positively correlated with the SLEDAI and ECLAM scores. The expression of LAIR -1 on pDCs of jSLE patients was significantly lower than that of HCs. In conclusion, our findings indicate that serum HMGB1 not only represents a potential marker of disease activity but together with the lack of LAIR-1 inhibitory function may contribute to the sustained inflammatory action of IFN-α in jSLE. In this regard, blocking the action of HMGB1 and its receptors or enhancing the expression/inhibitory function of LAIR-1 on pDCs should be included in future immune interventions for controlling jSLE.

Investigating the Economic Impacts of New Public Pharmaceutical Policies in Greece: Focusing on Price Reductions and Cost-Sharing Rates.

OBJECTIVE: Since 2010, cost-containment efforts in Greece focused on the reduction of public pharmaceutical expenditure. Changes in cost-sharing levels, reductions in prices, and generic substitution are some of the measures implemented after the second quarter of 2012. The objective of this study was to investigate the economic impact of the measures on public funds and households. METHODS: Data on volume and value for prescribed drugs for each therapeutic category and cost-sharing levels were obtained from the National Organization for Health Care Services Provision (EOPYY), the main reimbursement agency covering 95% of the population. Four different periods were compared, taking into consideration the implementation of different regulation, data availability, and disease seasonality. The periods compared were January-March 2012 versus January-March 2013 and April-August 2012 versus April-August 2013. RESULTS: In 2013, only 8% of prescribed drug boxes were provided with 0% cosharing arrangement versus 13% in 2012. Α 25% cost-sharing level was imposed on 77% of the prescribed medicines in 2013 compared with 53% in 2012. Consequently, the mean cost-sharing burden for pharmaceuticals in 2013 was estimated at 18% versus 13.3% in 2012. The average price per package declined in 2013 by 28%, from €17.8 in 2012 to €12.8 in 2013. Major (>50%) savings were achieved in cardiovascular and nervous system drugs, accounting in volume for almost 60% of total pharmaceutical consumption. CONCLUSIONS: The economic results of the measures for third-party payers were positive. The measures, however, should be reconsidered and examined more closely considering social effects, such as accessibility, especially for vulnerable groups in need of essential pharmaceutical care.

Immune cells after prolonged Natalizumab therapy: implications for effectiveness and safety.

BACKGROUND: Previous studies on Natalizumab (NAT) have shown increased circulation of most white blood cells (WBC) in multiple sclerosis (MS) patients shortly after its introduction. AIM: To describe peripheral immune cell phenotypes after more than 2 years of continuous NAT therapy and test for associations with clinical response to therapy. METHODS: Peripheral immune cell subsets were analyzed in 44 NAT-MS patients receiving NAT for over 24 months, and in 22 NAT-free control-MS patients. RESULTS: NAT-MS patients displayed significantly higher numbers of all WBC when compared with controls. B lymphocytes exhibited a more pronounced increase when compared with CD4+, CD8+ and NK T-cells (P = 0.011). CD4/CD8 ratio was significantly decreased in NAT-MS patients (P = 0.018) and showed no correlation with the number of NAT doses. The reduced CD4/CD8 ratio was attributable to the 'EDSS improvement' group only, irrespective of age, sex and disease severity. CONCLUSIONS: The study suggests that there is no desensitization effect after prolonged NAT exposure. A reduced CD4/CD8 ratio was associated with long-term response to therapy; thus, those patients who most benefitted from the drug might be at greater risk for opportunistic infections like progressive multifocal leucoencephalopathy (PML). We provide implications for future research for the CD4/CD8 ratio as a possible contributor to the recently developed risk stratification scheme for PML.

A strategy of splitting individual high volume cord blood units into two half subunits prior to processing increases the recovery of cells and facilitates ex vivo expansion of the infused haematopoietic progenitor cells in adults.

This study was designed to maximize the recovery of the desirable cell populations contained in the cord blood (CB) freezing bag, in order to optimize donor selection for adolescents and adults. To evaluate this hypothesis, high volume CB units (CBUs) were categorized into three volume collection groups (120-139, 140-159 and >or=160 ml) and were randomly split before volume reduction into two half low volume CBUs; (a) and (b). Using the SEPAX Cell Processing System, all CBUs were standardized to 26 ml. In 128 high volume split CBUs, the WBC, mononuclear cell and CD34+ cell recoveries were significantly higher (P

p16 inactivation associated with aggressive clinical course and fatal outcome in TEL/AML1-positive acute lymphoblastic leukemia.

The authors describe a 7-year-old boy with TEL/AML1-positive pre-B acute lymphoblastic leukemia, with hemizygous 9p21 deletion at presentation and no p16(INK4A) protein expression. Despite an initial response to a standard chemotherapy regimen, the patient suffered two hematologic relapses and died 34 months after diagnosis. The authors discuss the possibility that complete p16(INK4A) gene inactivation may adversely modify the prognostic significance of TEL/AML1 fusion in childhood acute lymphoblastic leukemia, and present evidence from clinical and in vitro observations in favor of this assumption.

Kinetics of quiescent cord blood stem/progenitor cells with high proliferative potential in stem-cell expansion culture.

BACKGROUND: The most primitive engrafting hematopoietic stem cell (HSC) resides mainly in a tumor growth factor-beta (TGF-beta)-dependent quiescent phase of the cell cycle. In this study, ex vivo expansion of UC blood (UCB) HSCs has been investigated, with the aim of showing whether quiescent HSCs can be recovered from expansion culture. METHODS: AC133(+) stem/progenitor cells from six full term-pregnancies UCB-samples were immunomagnetically selected, followed by ex vivo expansion culture in the presence of thrombopoietin (TPO), c-kit ligand (KL), flt-3 ligand (FL) and IL-6. Quiescent HSCs were detected by a clonogenic assay that allows the detection of multipotent and committed single- lineage quiescent stem/progenitor cells, named mHPP-Q and cHPP-Q, respectively, by means of a TGF-beta blocking Ab. RESULTS: Expansion culture of fresh selected AC133(+) cells for 1 week caused maintenance rather than expansion of mHPP-Q cells and a 1-fold increase in cHPP-Q cells. A further week culture initiated with 7-day expanded AC133(+) cells resulted in an additional 1.5-fold expansion of cHPP-Q while no mHPP-Q cells could be detected. Amplification of cHPP-Q cells in long-term expansion cultures initiated with 14-day expanded AC133(+) cells was observed for at least a further 4 weeks. DISCUSSION: A small proportion of HPP-Q cells recovered from 7-day expansion cultures retain their multilineage potential: longer culturing of these cells results in the loss of multilineage potential while they maintain quiescent behavior and high proliferative potential.

An unusual case of CD4+ CD7+ CD56+ acute leukemia with overlapping features of type 2 dendritic cell (DC2) and myeloid/NK cell precursor acute leukemia.

Type 2 dendritic cell (DC2) acute leukemia has been recently described. We report here an unusual case of a 17-yr-old adolescent with overlapping features of DC2 and myeloid/NK cell precursor acute leukemia as defined by Suzuki et al. The patient presented with lymphadenopathy and hepatosplenomegaly without extranodal manifestations in skin or elsewhere. The morphologic, cytochemical and immunophenotypic features were compatible with those described in DC2 acute leukemia, with co-expression of CD4, CD56 and CD123 antigens. The novel markers BDCA-4 and BDCA-2 considered specific for DC2s were co-expressed. However, bright CD7 positivity along with a dim expression of CD33 (57%) and CD117 (27%) were also noted. Additionally, there was bright expression of NG2 monoclonal antibody 7.1, a frequent finding in myeloid/NK cell precursor acute leukemia. The interpretation of the immunophenotypic profile leads to the hypothesis on the existence of borderline cases between DC2 and myeloid/NK cell precursor acute leukemia. Still, other hypotheses can not be overlooked, such as the possibility for a kind of variant monoblastic leukemia or of another rare entity of acute unclassified leukemia.

Evidence for T-large granular lymphocyte-mediated neutropenia in Rituximab-treated lymphoma patients: report of two cases.

We report two cases with B cell malignancies (case #1: refractory mantle cell lymphoma; case #2: lymphocyte predominant Hodgkin's disease (LPHD)) who developed neutropenia post-Rituximab therapy in a setting of significant infiltration of the peripheral blood (PB) and bone marrow (BM) by T cells with an immunophenotype of large granular lymphocytes. Possible pathogenetic mechanisms are discussed.

Molecular analysis of transferrin receptor mRNA expression in acute myeloid leukaemia.

Transferrin receptor (TfR, CD71) is an integral membrane glycoprotein that mediates cellular uptake of iron. In most tissues, TfR expression is correlated positively with proliferation and regulated at the post-transcriptional level. The available data regarding the pattern of TfR gene expression in haematological malignancies are very limited. In the present study, we evaluated TfR gene expression at the molecular level in bone marrow (BM) samples of 44 patients with de novo acute myeloid leukaemia (AML) at diagnosis with BM blasts > 85%. TfR mRNA levels were determined by densitometric analysis of quantitative reverse transcription polymerase chain reaction products corresponding to TfR exons 15-17. Each sample was tested in at least two independent experiments. In 13/44 patients, TfR messages were not detected (this is probably an underestimate as some positive results may be attributed to residual normal erythroid cells present in the samples). In 17/44, TfR mRNA levels were low-intermediate, and were high in the remaining patients (14/44). TfR mRNA positivity was significantly associated with older age. No statistically significant correlations were found either with specific French-American-British (FAB) subtypes or attainment of complete remission, incidence of relapse and survival (after adjusting accordingly for age and FAB subtype). The absence of TfR mRNA transcripts in a significant minority of cases suggests that alternative mechanisms of iron uptake may function in AML blast cells.