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Pandanus amaryllifolius Roxb. leaf has a natural mouthwash used as an alternative to commercial mouthwash. The purpose of this study was to determine the potential of giving scented Pandan leaf extract (Pandanus amaryllifolius Roxb.) using nanoemulsion technique as a natural mouthwash. This study used an experimental method with a trial of Completely Randomized Design (CRD) with five treatments and five replications. Data were analysed using Analysis of variance Test and Duncan at α=0.01 (99% confidence level). The result of giving 21-day natural mouthwash showed that P3 (4% extract) has the average salivary pH higher than the value of P1 (1% extract) and P2 (2 % extract), and the average salivary pH value of P3 (4% extract) approached the average salivary pH of P0+ (commercial mouthwash). Besides, there was a significant effect of 21-day of treatment to the respondents that is showed by F (4.20) = 20.57, ρ (0.01) = 4.43. The conclusion of this study is the administration of P amaryllifolius extract with nanoemulsion technique can be used as a natural mouthwash which is to maintain the salivary pH.

Carp ( Cyprinus carpio ) is one of important freshwater cultivated fish species in Indonesia. Aeromonas hydrophila is accounted as potential pathogenic bacteria in Carp, Hence the control for the infection of A. hydrophila is very important. In this study we investigated the effectiveness of crude extract of Dayak onions (Eleutherine palmifolia (L.) Merr) for the treatment of A. hydrophila infected fish. Furthermore, alteration of histophatology of several organs, gills, kidney, liver and muscle were also investigated. Crude Extract of Dayak Onion ( E leutherine palmifolia (L) Merr. (CEDO) with the doses of 50, 60, 70 and 80 ppm were used for treatment of A. hydrophila infected carp for 11 days. Prior to investigation of histopatology of gills, kidneys, hearts, muscle, the Carp was moved to fresh-non infected fish tank. The Result indicated that gill experienced Hyperplasia, Fusion, Necrosis. Kidney experienced Degeneration, Congestion, Necrosis. Liver experienced the vacuole degeneration, congestion, Melano macrophages, necrosis. Muscle experienced Edema and necrosis. But fish treated with 80 ppm treatment showed less damage and tissue repair. Keywords : E. palmfolia (L.) Merr, A. hydrophila , C. carpio , Histopathology, Gills, Kidney, Liver, Muscle

After an experimental phase of many years, 3D filming is now effective and successful. Improvements are still possible, but the film industry achieved memorable success on 3D movie’s box offices due to the overall quality of its products. Special environments such as space ("Gravity") and the underwater realm look perfect to be reproduced in 3D. "Filming in space" was possible in "Gravity" using special effects and computer graphic. The underwater realm is still difficult to be handled. Underwater filming in 3D was not that easy and effective as filming in 2D, since not long ago. After almost 3 years of research, a French, Austrian and Italian team realized a perfect tool to film underwater, in 3D, without any constrains. This allows filmmakers to bring the audience deep inside an environment where they most probably will never have the chance to be.

Background: Clinical and molecular factors are essential to define the prognosis in patients with glioblastoma (GBM). O6-methylguanine-DNA methyltransferase (MGMT) methylation status, age, Karnofsky Performance Status (KPS), and extent of surgical resection are the most relevant prognostic factors. Our investigation of the role of gender in predicting prognosis shows a slight survival advantage for female patients. Methods: We performed a prospective evaluation of the Project of Emilia Romagna on Neuro-Oncology (PERNO) registry to identify prognostic factors in patients with GBM who received standard treatment. Results: A total of 169 patients (99 males [58.6%] and 70 females [41.4%]) were evaluated prospectively. MGMT methylation was evaluable in 140 patients. Among the male patients, 36 were MGMT methylated (25.7%) and 47 were unmethylated (33.6%); among the female patients, 32 were methylated (22.9%) and 25 were unmethylated (17.9%). Survival was longer in the methylated females compared with the methylated males (P = 0.028) but was not significantly different between the unmethylated females and the unmethylated males (P = 0.395). In multivariate analysis, gender and MGMT methylation status considered together (methylated females vs. methylated males; hazard ratio [HR], 0.459; 95% confidence interval [CI], 0.242-0.827; P = 0.017), age (HR, 1.025; 95% CI, 1.002-1.049; P = 0.032), and KPS (HR, 0.965; 95% CI, 0.948-0.982; P < 0.001) were significantly correlated with survival. Conclusions: Survival was consistently longer among MGMT methylated females compared with males. Gender can be considered as a further prognostic factor.

One of the major challenges of antitumor drugs delivery is the development of suitable carriers for therapeutic molecules. Superparamagnetic iron oxide nanoparticles (SPIONs) are promising magnetic drug carriers as they are biocompatible, biodegradable, readily tunable in size and shape, and controllable by external magnetic fields. We propose and demonstrate the possible synthesis of bioinspired polydopamine-functionalized superparamagnetic clusters (MNC@PDO) to be applied to the anticancer drug cisplatin [cis-dichloro-diammino-platinum(II), CDDP] loading and delivery processes. For these specific nanosystems the drug release capacity has been tested. In this context, the first synthetic step is based on an oil-phase evaporation-induced self-assembly strategy, to fabricate the magnetic nanocrystal clusters (MNC). We demonstrated that for the choice of the best size and volume of SPIONs, the adopted solvent and the surfactant concentration are very important parameters. With this strategy, we can produce nanoclusters with a high density of magnetic cores, a size comprised between 90 and 100 nm, and a multilayer structure. Secondly, the surface of the MNCs was functionalized with polydopamine (PDO) for improving their stability, moreover different concentrations of dopamine were assayed to determine the best compromise between stability of the clusters and loading capacity. Finally, the CDDP was grafted to the surface of stable MNC@PDO systems (MNC@PDO-CDDP), studying its release efficiency from these nanoparticles. The MNC@PDO systems reveal to be promising models for the uptake and specific tissue delivery of chemotherapeutic drugs, in antitumor therapy. Moreover, the MNC@PDO nanosytems show a pH-responsive behaviour of great significance in controlled drug delivery and targeting of specific sites.

The recent trend toward drilling horizontal wells with complicated geometries in complex reservoirs has led to operational challenges. While LWD logs are often well suited in these environments, circumstances such as very small wellbores, tool availability, and high costs sometimes lead to a search for alternative means of acquiring a full suite of formation evaluation data. The objective of this paper is to show how, in a very complex reservoir, the choice of conveyance system can be strategic, particularly in the context of data quality and risk mitigation. The conveyance system considered is comprised of wireline tools which are housed inside drill pipe. When the borehole assembly reaches the toe of the lateral, a dart is pumped down, which releases the formation evaluation assembly and turns on the data acquisition. As the pipe is tripped out of the hole, the tools acquire data in memory. The presented case study considers a field in Southern Europe where a fractured carbonate reservoir is developed with horizontal wells. Characteristics of the reservoir are very high resistivity, wellbore stability issues, presence of asphaltenes, and 6″ bit sizes. To fully characterize the reservoir properties and understand the natural fracture networks, electrical imaging, gamma-ray, dipole sonic and caliper data were acquired. The integration of the dipole sonic and electric image logs provided the basic information to perform the matrix and the fractures evaluation as well as the anisotropy orientation and the best fluid path characterization. The availability of mechanical caliper led the decrease of the uncertainty in the interpretation and the optimization of the lower completion placement. A comparison between LWD and WL image logs is presented to rate the real added value of the wireline acquisition. This new approach using an alternative conveyance system enabled proper reservoir characterization. In addition to the high quality of the results there was also a reduced exposure to potential risks including stuck and lost in hole tools. The general pros and cons as well as cost considerations are discussed. While the conveyance system is generally considered a drilling focused solution and is therefore most influenced by operational challenges, it should also be considered an additional resource for the petrophysicist and geologist performing essential data interpretation as proven by the presented case study.

Concerning food safety, the interest for smart and portable biosensor is growing. On the other side, current commercial solution still does not reach performance comparable to laboratory test. Micro-ELISA is a smart portable biosensor useful in implementing the paradigms of the Process Analytical Technology (PAT) to the food industry. The use of this biosensor device (Lab-On-a-Chip disposable card, LOC) is a promising tool devoted to the detection of biotic and abiotic contaminant during the whole food supply chain with the accuracy and precision of laboratory methods. Micro-ELISA probes are based on affinity biomolecules, both antibodies and aptamers can be used. Some examples of applications − obtained from the project “Food Digital Monitoring”, supported by structural and National funds for Regional Development — are reported: lysozyme as food allergen and aflatoxin B1 as food contaminant.

Shell foundations are increasingly adopted around the world as an economic alternative to traditional flat foundations. Evidence of increased bearing capacity and reduction in settlement behavior exhibited by shell footings, coupled with their high potential resistance to seismic loading and sustained lateral earth pressure is valuable in terms of their geotechnical response. Nevertheless, practical use of shell footings is trailing behind conventional foundation structures due to lagging research on the performance and application of these foundations.

This article discusses the exploitation of specific proteins for engineeringnanoelectronic devices. It begins with an overview of the basic characteristics of proteins as well as the main procedures and strategies in nanomanufacturing suitable for interfacing inorganic matter to biological units. It then considers nanoelectronic devices having proteins as functional units as well as the biophysical implications of protein-based nanobioelectronics. It also highlights major concerns about the possibility of integrating nanodevices with the present-day consumer electronics. Finally, it describes recent developments in thefields of biosensing and proteomics, along with the related technological methods in realizing hybrid devices and biocompatible interfaces.

Polyelectrolyte multilayer (PEM) capsules engineered with active elements for targeting, labeling, sensing and delivery hold great promise for the controlled delivery of drugs and the development of new sensing platforms. PEM capsules composed of biodegradable polyelectrolytes are fabricated for intracellular delivery of encapsulated cargo (for example peptides, enzymes, DNA, and drugs) through gradual biodegradation of the shell components. PEM capsules with shells responsive to environmental or physical stimuli are exploited to control drug release. In the presence of appropriate triggers (e.g., pH variation or light irradiation) the pores of the multilayer shell are unlocked, leading to the controlled release of encapsulated cargos. By loading sensing elements in the capsules interior, PEM capsules sensitive to biological analytes, such as ions and metabolites, are assembled and used to detect analyte concentration changes in the surrounding environment. This Review aims to evaluate the current state of PEM capsules for drug delivery and sensing applications. © 2014 Elsevier B.V.

Introduction Current treatment options for myelofibrosis (MF) are diverse; apart from rare patients who are eligible for allogeneic transplantation, active treatments are focused on controlling MF-related symptoms and are not disease modifying. Patients who are initially asymptomatic and those at low risk for progression are usually observed without active treatment (watch and wait) until the appearance of symptoms or progression. There are limited real-world data on the management of patients with MF in the United Kingdom (UK). The REALISM UK study documented the early management pathways for patients with MF in routine clinical practice. Method REALISM UK was a multi-centre, retrospective, non-interventional study in 15 UK secondary care centres. Eligible patients were those aged ≥18 years at diagnosis of MF, with diagnosis >6 months and ≤5 years prior to data collection and with ≥1 follow-up visit. Data on patient demographics, clinical characteristics, MF management strategies and outcomes were collected from patients' medical records; the observation period was from the date of MF diagnosis until data collection. The primary endpoint was the time from diagnosis to active treatment. Watch and wait strategies included supportive therapies (blood transfusions, erythropoiesis-stimulating agents, and steroids). Results A total of 200 patients were recruited (63% [n=126/200] with primary MF (PMF); 37% [n=74/200] with secondary MF). The median age at MF diagnosis was 69.7 years (interquartile range [IQR] 63.5-75.7) and 71% (n=141/200) had a JAK2 mutation. At diagnosis, 52% (n=104/200) of patients had International Prognostic Scoring System (IPSS) categories of intermediate-2 (Int-2) or high. Common documented features of disease at diagnosis included an enlarged spleen (47%, n=94/200), anaemia (44%, n=88/200), and constitutional symptoms (e.g. night sweats, unexplained fever, or weight loss [30%, n=60/200]). The median (IQR) time to first active treatment was 46 days (range 0-350) in the total population; patients with higher risk disease were prescribed active treatment sooner: IPSS low, 136.5 days (range 0-625; n=26); IPSS Int-1, 90 days (range 0-494; n=70); IPSS Int-2, 0 days (range 0-252; n=65); IPSS high: 0 days (0-216; n=39). The choice of first management strategy by IPSS at diagnosis is shown in Table 1. During the study period, watch and wait was the first management strategy for 54% (n=107/200) of patients, with the median (IQR) time from diagnosis to active treatment in this group being 322 (130-610) days. Constitutional symptoms were recorded in 20% (n=21/107) of patients for whom watch and wait was the first management strategy. Active treatment was started at diagnosis for 47% (n=93/200) of patients, with the most commonly used medications being hydroxycarbamide (22.5% [n=45/200]) and ruxolitinib (17.5% [n=35/200]). The median (IQR) treatment duration during the study observation window was 346 days (range 121-768) for hydroxycarbamide and 375 days (range 172-691) for ruxolitinib. In total, 5.5% (n=11/200) of patients were recorded as having undergone allogenic stem cell transplantation during the observation period. Conclusion Clinicians in the UK apply a broad range of management strategies for the treatment of patients with MF. Many patients were observed without active treatment following diagnosis, despite having symptomatic disease. The most common active treatments as first management strategies were hydroxycarbamide and ruxolitinib. Disclosures Mead: Pfizer: Consultancy; Novartis: Consultancy, Honoraria, Other: Travel/accommodation expenses, Research Funding, Speakers Bureau; Bristol Myers-Squibb: Consultancy. Somervaille:Novartis: Consultancy, Honoraria. Butt:Novartis: Consultancy, Honoraria, Speakers Bureau. Whiteway:Novartis: Consultancy, Honoraria, Speakers Bureau. Kirkpatrick:Novartis: Consultancy, Honoraria. Roughley:Novartis: Consultancy, Honoraria. Ewing:Novartis: Honoraria, Other: Meeting attendance sponsorship ; Bristol Myers-Squibb: Other: Meeting attendance sponsorship . Garg:Novartis: Consultancy, Honoraria. Harrison:Promedior: Honoraria; Shire: Speakers Bureau; Sierra Oncology: Honoraria; Celgene: Honoraria, Speakers Bureau; Roche: Honoraria; Novartis: Honoraria, Research Funding, Speakers Bureau; Incyte: Speakers Bureau; Gilead: Speakers Bureau; CTI: Speakers Bureau; AOP: Honoraria; Janssen: Speakers Bureau. Bains:Novartis: Employment. Chiu:Novartis: Employment. Hickey:OPEN VIE: Employment.

This study aims to determine the application of regulations related to work safety equipment and its availability on purse seine vessels in the Ocean Fisheries Port (PPS) of Kutaraja, Banda Aceh, and to find out fishermen's perceptions of the importance of work safety equipment. This research was conducted in July 2018, using the method of direct surveys and interviews concerning existing national regulations. Data were analyzed descriptively and linear regression analysis through SPSS program. The results showed that from all samples of vessels 11 GT-> 61 GT (n = 21) the percentage of the presence or application of safety devices on purse seine vessels was 63%. In the 11 GT - 20 GT category the existence or application of safety equipment is 45% (n = 3), on the 21 GT - 30 GT vessel is 60% (n = 6), on the 30 GT - 50 GT ship is 65% (n = 7), on vessels 51 GT - 60 GT is 57% (n = 3) and on vessels larger than 61 GT is 86% (n = 2). In general, fishermen already understand the importance of work safety equipment, but the availability and number of occupational safety equipment on the ship are inadequate. Safety tools (independent) work influences the perception of fishermen (dependent) of only 1.83%, the rest of 98.17% is influenced by other factors outside the availability of work safety tools.

The coralligenous habitats found in the Mediterranean Sea are hotspots comparable in biodiversity to tropical reefs. Coralligenous reefs are vulnerable to many human pressures, thus they are among the most threatened habitats in the Mediterranean Sea. In this study, we assessed the impacts on coralligenous habitats of activities associated with salvaging the wreck of the Costa Concordia cruise ship. After its partial foundering in 2012, the Costa Concordia remained adjacent to the eastern coast of Giglio Island (Tuscany, Italy), in the Tyrrhenian Sea, for over two years. Its salvage required high-impact engineering works, during the course of which monitoring of benthic communities was undertaken. We performed Rapid Visual Assessment (RVA) sampling (using recorded video) from 17 stations located between 35 and 76 m depth and characterized by coralligenous habitats. Sampling activity was performed during the summers of 2012, 2013, and 2014. In parallel, chemical and physical water parameters were measured continuously from summer 2012 to the end of summer 2014, in order to detect any perturbation in natural conditions caused by salvage activities. We assessed the ecological quality of coralligenous habitats by applying the COARSE (COralligenous Assessment by ReefScape Estimate) index, based on the RVA approach. Slight modifications were applied to one of the descriptors of the COARSE index in order to adjust for study site features. There was clear evidence of a reduction in coralligenous habitats quality. Assemblages, slope, type of pressure, and distance from the source of disturbance played a pivotal role in characterizing bottom quality. The index was shown to have an easy and cost-effective application, even in waters deeper than its calibration specification; furthermore, the modification reported here may increase its potential applications.

Congenital muscular dystrophies due to defects in genes encoding proteins involved in α-dystroglycan (α-DG) glycosylation are a heterogeneous group of muscle disorders variably associated with central nervous system and eye abnormalities. One of the more severe is muscle-eye-brain disease (MEB). Mutations in genes coding for proven or putative glycosyltransferases (POMT1, POMT2, POMGnT1, fukutin, FKRP, and LARGE), the DPM3 gene encoding a DOL-P-Man synthase subunit, and the DAG1 gene encoding α-dystroglycan, have been associated with altered α-DG glycosylation. We report new POMGnT1 mutations and evaluate protein expression in 3 patients and 2 foetuses with variably severe MEB features. We identify two new point mutations (c.643 C > T, c.1863delC), one new intragenic rearrangement (deletion of exons 2–8), and a new intron retention (between exons 21 and 22) resulting from a known point mutation c.1895 + 1 G > T. Our study provides further evidence that rearrangements of the POMGnT1 gene are relatively common. Importantly, if heterozygous, they can be missed on standard genomic DNA sequencing. POMGNT1 protein analysis in 3 patients showed that the severity of the phenotype does not correlate with protein expression. Cerebral MRI is important for identifying MEB and α-dystroglycanopathy phenotypes in children and foetuses, and hence for directing the genetic analysis.

Nutritional quality of fresh-cut produce is very important for the consumer. Its evaluation may be expensive and time-consuming for the industry, which conversely can easily determine changes in external appearance including color. The aim of this work was to find possible relationships between degradation of appearance attributes and the retained nutritional content of fresh-cut 'Cantaloupe' melons. Melon pieces were stored for 8 days in air at 5°C and 99% RH. Initially and after 1, 2, 3, 7 and 8 days of storage external (color, appearance score) and internal (acidity, soluble solids, fructose content, vitamin C, phenolic, antioxidant activity) quality parameters were monitored. For each parameter a degradation curve over time was obtained, which was fitted to zero and first order kinetics. For most of the quality parameters degradation patterns followed a kinetic of the first order, antioxidant activity and soluble solids could not be described by any significant kinetic. The appearance score showed the highest kinetic rate (0.17 day-1), followed by titratable acidity (0.09 day-1) and vitamin C (0.06 day-1). Score 3 and 2, which were defined as the limits of marketability and edibility, respectively, were used as reference for comparing the percentage of quality changes over time. When melon pieces reached score 3 that corresponded to 40% of initial variation, acidity increased of 39% and vitamin C decreased by 20%. When score reached a value of 2 (60% of variation), acidity increased by 73% and vitamin C decreased by 30%. Further research about different storage conditions and melon cultivars is needed in order to confirm the relationship between simple quality indicators linked to appearance degradation and nutritional quality of fresh-cut melon.

Summary. A multicentre cross-sectional survey was performed to provide an accurate picture of patients with chronic hepatitis B (CHB) cared for by Italian Infectious Diseases Centers (IDCs). This analysis describes factors associated with access to the treatment of CHB in a country where barriers to treatment are not expected to exist because of comprehensive coverage under the National Health System (NHS). The study was performed in 74 IDCs. The analysis focused on 3305 patients with CHB of 3760 HBsAg-positive patients enrolled from March to September, 2008. To account for missing values, a Multiple Imputation method was used. Treatment was reported in 2091 (63.3%) patients. In the multivariate analysis, an increased chance of getting treatment was independently associated with 10 years increase of age at diagnosis (adjusted odds ratio [aOR] 1.2, 95% confidence interval [CI] 1.1–1.3, P

I cambiamenti che si verificano durante l’invecchiamento sono stati spesso attribuiti anche alla mancanza di uno o piu ormoni. Occorre distinguere tra le modifiche del sistema ormonale connesse all’eta e quelle successive a malattie che sono piu frequenti nell’eta avanzata. Con l’esclusione della funzione tiroidea, trattata da un’altra relazione su questo volume, l’unico sistema endocrino per cui sono chiare le modifiche con l’eta e rappresentato da sistema ipotalo-ipofisi-gonadi nelle donne. In realta, anche il sistema degli ormoni della crescita (GH-IGF-1), ipofisi-gonadi nel maschio e il sistema ipofisi-surrene relativo alla produzione di deidroepiandrosterone solfato declinano lentamente ma progressivamente con l’avanzare dell’eta. Nuovi e interessanti studi sono in corso sulla regolazione nutrizionale dell’anziano, riguardanti il metabolismo glucidico e ormoni come la leptina e l’adiponectina, che potranno definire meglio l’andamento di questi ormoni in eta avanzata e le conseguenze cliniche di queste modificazioni.

The objective of this work was to verify the effect of cold storage and controlled atmosphere (CA) on long term storage of olives in relation to quality parameters of the extracted oil. 'Coratina', 'Leccino' and 'Ogliarola leccese' olives were stored in air at ambient temperatures (approximately 15 to 20°C), air at 5°C, and 2% O 2 in nitrogen at 5°C, in two replicates for treatment. Initially, and after 15 and 30 day samples were taken, oil was extracted with a laboratory scale milling plant. Before milling, respiration rate was measured with the static system. The following quality attributes were measured on oil samples: acidity (related to the presence of free fatty acid), peroxide value (peroxides are the first products of oxidation), coefficients of specific extinction at 232 nm (related to the presence of products of primary oxidation) and 270 nm (related to the presence of products of secondary oxidation), and oil stability (Rancimat test). 'Leccino' and 'Ogliarola leccese' olives showed a high incidence of decay after 30 days of storage in room conditions. Cold storage and controlled atmosphere had a significant effect on slowing down the respiration rate, and therefore, the metabolic activity of the drupes for all cultivars. Results on oil samples show a strong effect of low temperature storage on quality attributes. Results show a good potential for application in the olive oil industry in order to preserve quality of the product and to lengthen the processing season, while not many additional benefits can be attributed to the use of low oxygen. The implementation of cold storage of the fruit in the olive oil industry may lead to a general increment of oil quality and to the decrease of the incidence of capital costs due to the extension of the extraction season.

Janus-activated kinase 2 (JAK2) mutations are common in myeloproliferative disorders; however, although they are detected in virtually all polycythemia vera patients, they are found in ∼50% of essential thrombocythemia (ET) patients, suggesting that converging pathways/abnormalities underlie the onset of ET. Recently, the chromosomal translocation 3;21, leading to the fusion gene AML1/MDS1/EVI1 (AME), was observed in an ET patient. After we forced the expression of AME in the bone marrow (BM) of C57BL/6J mice, all the reconstituted mice died of a disease with symptoms similar to ET with a latency of 8 to 16 months. Peripheral blood smears consistently showed an elevated number of dysplastic platelets with anisocytosis, degranulation, and giant size. Although the AME-positive mice did not harbor Jak2 mutations, the BM of most of them had significantly higher levels of activated Stat3 than the controls. With combined biochemical and biological assays we found that AME binds to the Stat3 promoter leading to its up-regulation. Signal transducers and activators of transcription 3 (STAT3) analysis of a small group of ET patients shows that in about half of the patients, there is STAT3 hyperactivation independently of JAK2 mutations, suggesting that the hyperactivation of STAT3 by JAK2 mutations or promoter activation may be a critical step in development of ET. [Cancer Res 2009;69(1):262–71]

A letter to the editor is presented related to the case where GATA1 is overexpressed in patients with essential thrombocythemia and polycythemia vera, but not in patients with primary myelofibrosis or chronic myelogenous leukemia.

The last 20 years have observed the proposal of several minimally invasive techniques for non-surgical treatment of thyroid nodules. This chapter describes, on the basis of our experience and of a brief literature review, the efficacy, safety, cost-effectiveness and current clinical indications of the first of these procedures: percutaneous ethanol injection (PEIT).

Recurring chromosomal translocations observed in human leukemia often result in the expression of fusion proteins that are DNA-binding transcription factors. These altered proteins acquire new dimerization properties that result in the assembly of inappropriate multimeric transcription complexes that deregulate hematopoietic programs and induce leukemogenesis. Recently, we reported that the fusion protein AML1/MDS1/EVI1 (AME), a product of a t(3;21)(q26;q22) associated with chronic myelogenous leukemia and acute myelogenous leukemia, displays a complex pattern of self-interaction. Here, we show that the 8th zinc finger motif of MDS1/EVI1 is an oligomerization domain involved not only in interaction of AME with itself but also in interactions with the parental proteins, RUNX1 and MDS1/EVI1, from which AME is generated. Because the 8th zinc finger motif is also present in the oncoprotein EVI1, we have evaluated the effects of the interaction between RUNX1 and EVI1 in vitro and in vivo. We found that in vitro, this interaction alters the ability of RUNX1 to bind to DNA and to regulate a reporter gene, whereas in vivo, the expression of the isolated 8th zinc finger motif of EVI1 is sufficient to block the granulocyte colony-stimulating factor–induced differentiation of 32Dcl3 cells, leading to cell death. As EVI1 is not detected in normal bone marrow cells, these data suggest that its inappropriate expression could contribute to hematopoietic transformation in part by a new mechanism that involves EVI1 association with key hematopoietic regulators, leading to their functional impairment. [Cancer Res 2007;67(12):5658–66]

Halloysite is a nanostructured clay mineral with hollow tubular structure, which has recently found an important role as delivery sistem for drugs or other active molecules. One of these is curcumin, main constituent in the rhizome of the plant Curcuma Longa, with a series of useful pharmacological activities, hindered by its poor solubility in water and bioavalaibility. In this study, Halloysite Clay Nanotubes (HNTs) were characterized in terms of both structure and biocompatibily and they were used for curcumin delivery to cancer cells. The performed MTT assay showed that HNTs have a high biocompatibility, also when coated with polymers, while curcumin is highly toxic for cancer cells. The release kinetics of curcumin from HNTs was investigated by the dialysis bag method, showing a slow and constant release of the drug, which can be further controlled by adding layers of polymers to the external surface of the tubes. The Trypan Blue assay showed a cytotoxic effect of loaded HNTs, proportional to the concentration of tubes and the incubation time.

EVI1 is an aggressive nuclear oncoprotein deregulated by recurring chromosomal abnormalities in myelodysplastic syndrome (MDS). The expression of the corresponding gene is a very poor prognostic marker for MDS patients and is associated with severe defects of the erythroid lineage. We have recently shown that the constitutive expression of EVI1 in murine bone marrow results in a fatal disease with features characteristic of MDS, including anemia, dyserythropoiesis, and dysmegakaryopoiesis. These lineages are regulated by the DNA-binding transcription factor GATA1. EVI1 has two zinc finger domains containing seven motifs at the N terminus and three motifs at the C terminus. Supported by results of assays utilizing synthetic DNA promoters, it was earlier proposed that erythroid-lineage repression by EVI1 is based on the ability of this protein to compete with GATA1 for DNA-binding sites, resulting in repression of gene activation by GATA1. Here, however, we show that EVI1 is unable to bind to classic GATA1 sites. To understand the mechanism utilized by EVI1 to repress erythropoiesis, we used a combination of biochemical assays, mutation analyses, and in vitro bone marrow differentiation. The results indicate that EVI1 interacts directly with the GATA1 protein rather than the DNA sequence. We further show that this protein-protein interaction blocks efficient recognition or binding to DNA by GATA1. Point mutations that disrupt the geometry of two zinc fingers of EVI1 abolish the protein-protein interaction, leading to normal erythroid differentiation of normal murine bone marrow in vitro.

Fresh tomatoes (cv. 'Camonium') at the breaker-turning color stage were stored at 12°C in air (i), air after exposure with 1-ppm 1-MCP for 24 h (ii), 2% O 2 + 3% CO 2 in nitrogen (iii), and in 2% O 2 + 3% CO 2 in nitrogen after exposure with 1-ppm 1-MCP for 24 h (iv). Initially and after 4, 6, 8, and 11 days of storage the following quality attributes were evaluated: color of the epicarp, berry relative deformation, total soluble solids, and titratable acidity. In addition, respiration rate was measured only for air treatments. Both controlled atmosphere and 1-MCP treatments significantly delayed color evolution and firmness loss. Treatment with 1-MCP also influenced respiration rate, total soluble solids and total soluble solids to titratable acidity ratio. Effect of 1-MCP on ripening was higher than effect of controlled atmosphere. The latter was noticeable only in fruit not treated with 1-MCP. Untreated fruit in air ripened faster than all other treatments, followed by untreated fruit in 2% O 2 + 3% CO 2 . No statistical difference was shown between berries treated with 0.5 ppm of 1-MCP for 24h and followed by storage in air or in controlled atmosphere.

Background: Cytotoxic regimens used in induction treatments for acute myeloid leukemia (AML) almost always include standard or high-dose cytarabine (Ara-C). During or soon after induction therapy, leukemic patients frequently develop gastroenteric complications, characterized by abdominal pain and diarrhea. The association ofthese symptoms with f and melena is typical ofnecrotizing enterocolitis (NE), a life-threathening condition that can be documented by ultrasound abdominal scan. Patients and methods: We analyzed retrospectively the clinical course of169 adult patients with AML treated by standard dose Ara-C-containing induction regimens, either by continuous venous infusion (group 1) or subcutaneous injection (group 2). Ultrasonography was employed as early diagnostic tool in a majority ofpatients with gastroenteric complications. Bowel wall thickening was accurately measured and used to confirm the diagnosis of necrotizing enterocolitis. Results: In the first group of 115 patients (median age, 51 years), gastroenteric complications were observed in 55 patients (48%), and 10 patients (9%) received diagnosis ofNE, which was fatal in four. Patients with NE had a median age older than that of patients without gastroenteric symptoms, and a more prolonged neutropenia. In the second group of54 patients (median age, 60 years), gastroenteric events were observed in 14 patients (26%), and no case of NE was recorded. Conclusions: This retrospective analysis shows that NE is a serious complication occurring mainly in patients treated by Ara-C administered as continuous i.v. infusion. The Hematology Journal (2003) 4, 346–350. doi:10.1038/sj.thj.6200304

The project PICAR (Cultural landscaPe and human Impact in Circum-mediterranean countries: multidisciplinary Archaeobotanical research for environmental, phylogeographic, climatic and virtual Reconstructions; Programmi di Ricerca Scientifica di Rilevante Interesse Nazionale 2008FJCEF4 - Italy) focuses on cultural landscape reconstructions and on the recognition of plants related to anthropic presence or activities in a territory (collected or cultivated economic plants; useful, including those that are currently neglected, plants; wild synanthropic plants). The focus is on the knowledge of the general response of environmental dynamics to human impact in the past, and on how different environments changed under the pressure of different civilizations. This communication will report some examples of the multidisciplinary archaeobotanical studies that the research team of the laboratory of Modena has carried out in the last years, mainly dealing with contexts from Italian archaeological sites. Pollen and macroremains analyses were and are commonly integrated with archaeological data. This methodology allows comparisons between different times and geographical areas giving new hints to human landscape reconstructions, by comparing in which way humans exploited plant resources in their territories, adapting them to the changing environment under the changing Holocene climate, and by transforming soils and vegetation according to their cultural needs.

Acute kidney injury (AKI) is an emergent public health problem that affects millions of patients worldwide. Several pharmacologic therapies that can accelerate recovery and improve survival were successful in experimental models but failed to manifest any significant beneficial effect in clinical practice [1]. Recent studies have indicated that adult renal stem/progenitor cells (ARPCs) are able to repair damaged renal proximal tubular epithelial cells (RPTECs) in AKI induced by toxic agents, via the secretion of both inhibin-A (INHB-A), FGF2 chemokines and specific microvesicle-vehicled mRNA [2]. Our goal was to synthesize a natural polymer-based nanosystem for efficacious delivery of INHB-A. Alginate (AL) and chitosan (CS), due to their promising properties are being exploited for the development of drug delivery systems [3]. INHB-Aloaded Polysaccharides Synthetic Vesicles (INHB-A-PSSV) were synthesized by two steps methods: ionotropic pre-gelation of AL core, followed by CS polyelectrolyte complexation. A microfluidic device was appositely fabricated in order to optimize the INHB-PSSV -at interface-assembly process, in terms of polymers and INHB-A working amount as well as vesicles size distribution. TEM and DLS characterization showed highly mono-disperse spherical PSSV ((157 ± 30) nm in diameter) and ?-potential measurement ((+56 ± 4) mV) confirmed the CS coating stability. Cellular uptake and INHB-A-PSSV effectiveness were tested in an in vitro model of cisplatin (CisPt) induced cell toxicity. RPTECs were exposed to 2.5 µmol/l CisPt for 6 h and, after drug withdrawal, cell viability was performed at 3 days after treatment. CisPt treated cell viability significantly decreased, compared with healthy control. We showed that addition of INHB-A-PSSV to CisPt -treated RPTECs led to a substantial increase in cell number and viability after 3 days of culture. Remarkably, a very low dosage of functional loaded protein (8 ng/25 µl) was sufficient to induce cell regeneration and the percentage of viable cells was similar to that of RPTECs without CisPt treatment.

Oxygen consumption rate (OCR) is a significant parameter helpful to determine in vitro respiratory efficiency of living cells. Oxygen is an excellent oxidant and its electrocatalytic reduction on a noble metal allows to accurately detect it. By means of micro fabrication technologies, handy, low-cost and disposable chip can be attained, minimizing working volumes and improving sensitivity and response-time. With this respect, here is presented a micro-oxygraph device (MOD), based on Clark's electrode principle, displaying many advantageous features comparing to other systems. This lab-on-chip platform is composed of: a three microelectrode detector equipped with a micro-grooved electrochemical cell, sealed with a polymeric reaction chamber. Standard photolithographic and thermal evaporation processes were used to fabricated Au working/counter electrodes and Ag/AgCl reference electrode on a glass slide. A micro-channel was realized by photoresist lift-off technique and a polydimethylsiloxane (PDMS) nano-porous membrane was integrated as oxygen permeable septum (OPM) between the probe and the micro reaction chamber. The chip was characterized by cyclic voltammetry, selecting a potential of -0.8 V for electrochemical measurement. Reproducibility (? response 0.54 µA ± 0.06 SD) and average response time (39.6 sec ± 0.5 SD) were assessed by periodic injection and suction of 0.1 M Na2S2O4. OCR measurements on 3T3 cells, subjected, in real time, to chemical stress on the respiratory chain were able to show that this chip lets to perform consistent metabolic analysis.

Reduction strategies of blood pressure, as a modifiable cardiovascular risk, are currently based on office assessment of brachial artery blood pressure. However, antihypertensive treatment based on brachial BP values reduces cardiovascular risk but cannot completely reverse the hypertension-induced risk of morbidity events. As is well known, BP varies in different arterial systems and invasive and non-invasive studies have demonstrated that brachial BP does not necessarily reflect central aortic BP. Emerging evidences now suggest that central pressure may predict cardiovascular diseases better than brachial BP; moreover, it may differently respond to certain antihypertensive drugs. The potential effects beyond peripheral BP control may be due to specific protective properties of different antihypertensive drugs in affecting central aortic pressure and arterial stiffness. Although data on direct cardiovascular benefit impact of central blood pressure treatment in randomized clinical trials are still lacking, it is likely that the improvement of quality of care and the individualized assessment of the hypertension-associated cardiovascular risk are achievable with the use of central hemodynamics. Therefore, basing antihypertensive treatment guidance on central pressures rather than on peripheral blood pressure may be the key for future antihypertensive strategies.

To propose a test to evaluate endothelial function, based on VO(2) on-transition kinetics in sub-anaerobic threshold (AT) constant load exercise, we tested healthy subjects and patients with ischemic-hypertensive cardiopathy by two cardiopulmonary tests on a cycle ergometer endowed with an electric motor to overcome initial inertia: a pre-test and, after at least 24 h, one 6 min constant load exercise at 90 % AT. We measured net phase 3 VO(2)-on kinetics and, by phase 2 time constant (tau), valued endothelial dysfunction. We found shorter tau in repeated tests, shorter time between first and second test, by persisting endothelium-dependent arteriolar vasodilatation and/or several other mechanisms. Reducing load to 80 % and 90 % AT did not produce significant changes in tau of healthy volunteers, while in heart patients an AT load of 70 %, compared to 80 % AT, shortened tau (delta=4.38+/-1.65 s, p=0.013). In heart patients, no correlation was found between NYHA class, ejection fraction (EF), and the two variables derived from incremental cycle cardio-pulmonary exercise, as well as between EF and tau; while NYHA class groups were well correlated with tau duration (r=0.92, p=0.0001). Doxazosin and tadalafil also significantly reduced tau. In conclusion, the O(2) consumption kinetics during the on-transition of constant load exercise below the anaerobic threshold are highly sensitive to endothelial function in muscular microcirculation, and constitute a marker for the evaluation of endothelial dysfunction.

Increasing the ease and the rapidity of processing in micro and nanotechnology is an ongoing task, which is pursued in both the academic environment for investigation of novel systems and in industry for fabrication of complex circuits on a large scale. In the field of nanoelectronics, the major challenge is to demonstrate a feasible method for device implementation based on individual nanosize objects, such as nanowires, nanotubes and nanocrystals. However, integrating these small objects in a macroscopic circuit is a difficult task. So far, nanostructures have been wired by highly sophisticated techniques not suitable for large-scale integration in macroscopic circuits, such as electron-beam lithography or focused ion-beam deposition. Here we present a 'one-pot' and rapid approach to electrically interconnect individual nanowires from random spatial distribution, with high spatial and positioning resolution and a remarkable reduction in overall fabrication time with respect to the other expensive and laborious techniques. The reliability of such technique is demonstrated by implementing a single semiconductor nanowire device

Inhomogeneous broadening is a long standing issue in the physics of nanostructures, in that it prevents the detailed assessment of their electronic and optical properties, and limits the performances of nanostructure based devices. Advances in scanning probe spectroscopies have recently permitted to overcome this problem, thus opening the way to a detailed understanding of the single nanostructure properties, by virtue of their unsurpassed capability to inject carriers or photons at local scale. In particular, luminescence spectroscopy and current-voltage spectroscopy following highly localized carrier injection by a scanning tunneling microscope into a single quantum dot (QD), are the methods of choice to overcome the inhomogeneous broadening effects due to size and compositional non-uniformity. In this way one can map the eigenstates of a single dot, elucidate the relationships between carrier injection, capture and recombination, investigate the dynamics of single-dot filling, the formation of excitons and charged excitons, the occurrence of dot-dot interactions leading to molecular states, and the diffusion of charges into neighboring dots in a grand ensemble.

The role of the substrate in influencing the structure and morphology of α,ω-dihexyl-quaterthiophene (DH4T) thin films grown by organic molecular beam deposition was investigated by means of atomic force microscopy (AFM) imaging and optical absorption measurements. Silica and potassium acid phthalate (KAP) substrates were selected as representative of inorganic amorphous and organic crystalline substrates, respectively. The film growth mechanism was found to depend on the flatness, cleanliness, and structure of the substrate, which influence the overgrown film.

In this talk I will report on nanotechnological strategies to fabricate electronic devices based on guanosines and guanosine-oligothiophenes complexes. Self assembled mono layers were produced by physisorption or chemisorption by cast deposition and slow solvent evaporation. Guanosine molecules were modified in order to promote their stable chemical anchoring onto gold or silicon surfaces. Molecular self assembled monolayers were tested by Atomic force microscopy and scanning force spectroscopy in order to check the ordering and aggregation properties of immobilized guanosines. Scanning tunneling spectroscopy in UHV were performed in order to map the electronic configuration and/or modification of guanosines and guanosine-complexes deposited onto conductive surfaces. On the base of these results both bare molecules and gold nanoparticles covered by guanosine ribbons were produced and trapped inside interdigitated electrodes and mesa junctions for I/V measurements and device formance testing.

Background As yet, no population-based prospective studies have been conducted to investigate the incidence and clinical outcome of glioblastoma (GBM) or the diffusion and impact of the current standard therapeutic approach in newly diagnosed patients younger than aged 70 years. Methods Data on all new cases of primary brain tumors observed from January 1, 2009, to December 31, 2010, in adults residing within the Emilia-Romagna region were recorded in a prospective registry in the Project of Emilia Romagna on Neuro-Oncology (PERNO). Based on the data from this registry, a prospective evaluation was made of the treatment efficacy and outcome in GBM patients. Results Two hundred sixty-seven GBM patients (median age, 64 y; range, 29–84 y) were enrolled. The median overall survival (OS) was 10.7 months (95% CI, 9.2–12.4). The 139 patients ≤aged 70 years who were given standard temozolomide treatment concomitant with and adjuvant to radiotherapy had a median OS of 16.4 months (95% CI, 14.0–18.5). With multivariate analysis, OS correlated significantly with KPS (HR = 0.458; 95% CI, 0.248–0.847; P = .0127), MGMT methylation status (HR = 0.612; 95% CI, 0.388–0.966; P = .0350), and treatment received in a high versus low-volume center (HR = 0.56; 95% CI, 0.328–0.986; P = .0446). Conclusions The median OS following standard temozolomide treatment concurrent with and adjuvant to radiotherapy given to (72.8% of) patients aged ≤70 years is consistent with findings reported from randomized phase III trials. The volume and expertise of the treatment center should be further investigated as a prognostic factor.

Although the clinical relevance of brachial blood pressure (BP) measurement for cardiovascular (CV) risk stratification is nowadays widely accepted, this approach can nevertheless present several limitations. Pulse pressure (PP) amplification accounts for the notable increase in PP from central to peripheral arterial sites. Target organs are more greatly exposed to central hemodynamic changes than peripheral organs. The pathophysiological significance of local BP pulsatility, which has a role in the pathogenesis of target organ damage in both the macro- and the microcirculation, may therefore not be accurately captured by brachial BP as traditionally evaluated with cuff measurements. The predictive value of central systolic BP and PP over brachial BP for major clinical outcomes has been demonstrated in the general population, in elderly adults and in patients at high CV risk, irrespective of the invasive or non-invasive methods used to assess central BP. Aortic stiffness, timing and intensity of wave reflections, and cardiac performance appear as major factors influencing central PP. Great emphasis has been placed on the role of aortic stiffness, disturbed arterial wave reflections and their intercorrelation in the pathophysiological mechanisms of CV diseases as well as on their capacity to predict target organ damage and clinical events. Comorbidities and age-related changes, together with gender-related specificities of arterial and cardiac parameters, are known to affect the predictive ability of central hemodynamics on individual CV risk.

Background Tachykinins (TKs) have been shown to be involved in the excitatory enteric motor pathway. This study aimed to examine the direct and nerve-mediated effect of specific NK 1 , NK 2 and NK 3 receptor agonists and antagonists in colonic preparations from control subjects and patients with idiopathic chronic constipation (ICC). Materials and methods Cumulative concentrations of Sar 9 Met(O 2 ) 11 substance P (selective NK 1 receptor agonist), [Ala 5 ,b-Ala 8 ]-neurokinin A (4-10) (selective NK 2 receptor agonist) and [MePhe 7 ]-neurokinin B (selective NK 3 receptor agonist) were tested on colonic circular muscle strips to evaluate the direct drug effects. In addition, in the presence of atropine, the role of TKs in the off-contraction that follows the typical inhibitory response evoked by low frequencies of electrical field stimulation (0.5-10 Hz, 20 V, 1 ms pulse trains lasting 1 min) was investigated. Results In control preparations, the rank order of potency was: NK 2 receptor-selective agonist > NK 3 receptor-selective agonist > NK 1 receptor-selective agonist. The off-contraction was found to be reduced by about 30-40% in colonic circular muscle from ICC patients with respect to controls. Incubation with the NK 1 receptor agonist did not modify the off-contraction measurements in either control or ICC preparations. Conversely, both NK 2 and NK 3 receptor agonists significantly (P < 0.01) increased the off-contraction in ICC preparations only. This increased response was fully antagonized by MEN-10627, a NK 2 and NK 3 receptor antagonist depending on the dose. Conclusions We may conclude that ICC is hyporesponsive to TKs and that the contractile reflex to distension is greatly reduced in ICC disease, but can be restored by incubation with NK 2 and NK 3 receptor agonists.

SummaryThe germination of mature seeds of olive (Olea europaea L.) from six cultivars was examined by recording the percent germination, rate of germination and the ability to produce ethylene. The effects of various treatments, namely thidiazuron (TDZ), a compound with cytokinin-like activity, 1-aminocyclopropane-l-carboxylic acid (ACC), and aminoethoxyvinylglycine (AVG), on these variates were also evaluated. The main characteristics of seed development were also defined in both ‘Moraiolo’ and ‘Canino’, following harvest on three dates, by determining the course of the dehydration process and the ability of the seeds to produce ethylene; the effect of maturity state on germination and ethylene production was clarified. In general, there were wide variations between the cultivars with no positive correlations between the examined parameters. Germination of untreated seeds (control) from all the cultivars was always accompanied by an increase in ethylene synthesis. The presence of ACC was not always effec...