Evaluation of synthesis conditions for plastic scintillation foils used to measure alpha- and beta-emitting radionuclides

Plastic scintillation foils of polystyrene and polycarbonate with a thickness between 45 and 200 μm, have been produced using the solvent evaporation method. PSfoils presented a reproducible thickness (10-20%). PSfoils were characterized by the measurement of 36Cl or 241Am. For 36Cl spectrum is located at medium energies since not all energy is deposited in the scintillator and not all betas interact with the foils. For 241Am the efficiency values are very high and spectrum is a sharp peak located at high energies. 222Rn absorption (LD and K) and desorption capacities of the PSfoils have been also evaluated

Hydrolase–like catalysis and structural resolution of natural products by a metal–organic framework

The exact chemical structure of non–crystallising natural products is still one of the main challenges in Natural Sciences. Despite tremendous advances in total synthesis, the absolute structural determination of a myriad of natural products with very sensitive chemical functionalities remains undone. Here, we show that a metal–organic framework (MOF) with alcohol–containing arms and adsorbed water, enables selective hydrolysis of glycosyl bonds, supramolecular order with the so–formed chiral fragments and absolute determination of the organic structure by single–crystal X–ray crystallography in a single operation. This combined strategy based on a biomimetic, cheap, robust and multigram available solid catalyst opens the door to determine the absolute configuration of ketal compounds regardless degradation sensitiveness, and also to design extremely–mild metal–free solid–catalysed processes without formal acid protons.This work was supported by the Ministero dell’Istruzione, dell’Università e della Ricerca (Italy) and the MINECO (Spain) (Projects CTQ2016-75671-P, CTQ 2017-86735-P, RTC-2017-6331-5, Severo Ochoa program SEV-2016-0683 and Excellence Unit “Maria de Maeztu” MDM-2015-0538). R.B. thanks the MIUR (Project PON R&I FSE-FESR 2014–2020) for grant. L.B wishes to thank Italian MIUR for grant n. AIM1899391–1 in the framework of the project “Azione I.2, Mobilità dei Ricercatori, PON R&I 2014–2020”. Thanks are also extended to the “2019 Post-doctoral Junior Leader-Retaining Fellowship, la Caixa Foundation (ID100010434 and fellowship code LCF/BQ/PR19/11700011” (J. F.- S.). S. S.-N. thanks ITQ for the concession of a contract. D.A. acknowledges the financial support of the Fondazione CARIPLO/“Economia Circolare: ricerca per un futuro sostenibile” 2019, Project code: 2019–2090, MOCA. E.P. acknowledges the financial support of the European Research Council under the European Union’s Horizon 2020 research and innovation program/ERC Grant Agreement No. 814804, MOF-reactors

Efficient inhibition of iron superoxide dismutase and of Trypanosoma cruzi growth by benzo[g]phthalazine derivatives functionalized with one or two imidazole rings

The synthesis and trypanosomatic behavior of a new series of 1,4-bis(alkylamino)benzo[g]phthalazines 1−4 containing the biologically significant imidazole ring are reported. In vitro antiparasitic activity against Trypanosoma cruzi epimastigotes is remarkable, especially for compound 2, whereas toxicity against Vero cells is very low. Conversion of epimastigotes to metacyclic forms in the presence of the tested compounds causes significant decreases in the amastigote and trypomastigote numbers. Fe-SOD inhibition is noteworthy, whereas effect on human Cu/Zn-SOD is negligible.The authors thank the Spanish CICYT for the financial support

1,4-Bis(alkylamino)benzo[g]phthalazines able to form dinuclear complexes of Cu(II) which as free ligands behave as SOD inhibitors and show efficient in vitro activity against Trypanosoma cruzi

The synthesis of a new series of 1,4-bis(alkylamino)benzo[g]phthalazines 1–3 is reported, and their ability to form dinuclear complexes with Cu(II) assayed. The geometry of the complexes is dependent on the nature of the electron-donor sites at the sidechains. Compounds 1 and 2, that contain sp3 or sp2 nitrogens at the end of the alkylamino groups, originate monopodal dinuclear complexes which seem to include endogenous OH bridges, and the sidechains seem to actively participate in complexation. However, the substitution of nitrogen by oxygen in 3 leads to a tripodal dinuclear complex in which the sidechains are not involved. The in vitro antiparasitic activity on Trypanosoma cruzi epimastigotes and amastigotes and the SOD activity inhibition have been evaluated for compounds 1–3, and, as expected, 1 and 2 show in all cases relevant results, whereas 3 is always the less active among the three substrates tested.The authors thank the Spanish Comision Interministerial de Ciencia y Tecnologia for the economical support given to this work (SAF99-0066)

Implementation of intelligent data acquisition system for ITER fast controllers using RIO devices.

A basic requirement of the data acquisition systems used in long pulse fusion experiments is the real time physical events detection in signals. Developing such applications is usually a complex task, so it is necessary to develop a set of hardware and software tools that simplify their implementation. This type of applications can be implemented in ITER using fast controllers. ITER is standardizing the architectures to be used for fast controller implementation. Until now the standards chosen are PXIe architectures (based on PCIe) for the hardware and EPICS middleware for the software. This work presents the methodology for implementing data acquisition and pre-processing using FPGA-based DAQ cards and how to integrate these in fast controllers using EPICS

In vivo trypanosomicidal activity of imidazole- or pyrazole-based benzo[ g ]phthalazine derivatives against acute and chronic phases of chagas disease

The in vivo trypanosomicidal activity of the imidazole-based benzo[g]phthalazine derivatives 1−4 and of the new related pyrazole-based compounds 5 and 6 has been studied in both the acute and chronic phases of Chagas disease. As a rule, compounds 1−6 were more active and less toxic than benznidazole in the two stages of the disease, and the monosubstituted derivatives 2, 4, and 6 were more effective than their disubstituted analogs. Feasible mechanisms of action of compounds 1−6 against the parasite have been explored by considering their inhibitory effect on the Fe-SOD enzyme, the nature of the excreted metabolites and the ultrastructural alterations produced. A complementary histopathological analysis has confirmed that the monosubstituted derivatives are less toxic than the reference drug, with the behavior of the imidazole-based compound 4 being especially noteworthy.The authors thank the Santander-Universidad Complutense Research Program (Grant GR58/08-921371-891), the Spanish MEC Project (Grant CGL2008-03687-E/BOS), and the MCINN Projects (CTQ2009-14288-C04-01 and Consolider CSD2010-00065) for financial support

Brote de legionelosis en Murcia en julio de 2001. La óptica de sanidad ambiental

The measures of intervention adopted for the study and control of the outbreak are exposed. 126 systems with risk were found (45 of them high risk): 70 water cooling towers or similar, 35 decorative fountains, 1 building site with earth movement and 20 air-water closed systems, distributed by risk criteria.Immediately were stopped: decorative fountains, washing down of streets, spray irrigation in parks and the building site.486 inspections and 1040 sample taking were executed, the cleaning and disinfection of water cooling towers and similar systems were ordered and closing if necessary.Afterwards, fills were replaced in water cooling tower which tested Lp positive.After the investigation of 339 systems, 57 (16.9%) tested Lp positive culture, 23 (6.8 %) water cooling towers and 31 (9.1 %) drinking water taps.Distribution by serotypes: LpS1 (62’3%), serotypes 2-14 (36’68%).LpS1Olda Olda (21’74%) was the most abundant followed by LpS1 Pontiac Philadelphia Lugano (18’84%), in contrast to LpS1 Pontiac Philadelphia Glasgow (1’45%), found only in one case although isolated in the 18 samples of patients.Culture and PCR were available in 355 cases, resulting in 30,8% sensitivity (confidence interval 95%, 25,1) and specificity 99,4±0,8.There are a big percentage of samples positives to Lp Sg1 and between them prevail Lp Pontiac Philadelphia, basically Lugano kind.The first disinfection doesn ́t eradicate all the contamination. The finding of 14 Lp positive systems after cleaning and disinfection process, with previous negative cultures, suggests a high analytical results variability and/or an inefficient first cleaning and disinfections of the system.The previous conclusions and the low sensitivity of the PCR test must be considered in future cases.Se exponen las medidas de intervención adoptadas para el estudio y control del brote. Se encontraron 126 instalaciones con riesgo (45 de ellas de alto): 70 torres de refrigeración y similares, 35 fuentes ornamentales, 1 obra con movimiento de tierra y 20 sistemas con circuito cerrado aire-agua, que se distribuyeron por categorías de riesgo.De forma inmediata se clausuraron: las fuentes ornamentales, el baldeo de calles y riegos por aspersión de parques y la obra.Se realizaron un total de 486 inspecciones y 1040 toma de muestras, ordenando la limpieza y desinfección de torres de refrigeración y similares y su clausura en caso necesario. Posteriormente, se cambio de relleno en torres de refrigeración positivas a Lp.Del total de instalaciones investigadas (339), en 57 (16’9%) se encontró un cultivo positivo a Lp. Distribución por tipo de instalación con cultivo positivo a Lp: en torres de refrigeración 23 (6’8%), en fuentes ornamentales 3 (7,32%) y en agua sanitaria 31 (9’1%).Distribución por serogrupos: LpS1 (62’3%), serogrupos 2-14 (36’68%).LpS1Olda Olda (21’74%) fue la mas abundante seguida de LpS1 Pontiac Filadelfia Lugano (18’84%) frente a LpS1 Pontiac Filadelfia Glasgow (en 1 ocasión, 1’45%), esta ultima fue la aislada en las 18 muestras de enfermos.En 355 ocasiones se dispone de cultivo y PCR, encontrándose una sensibilidad de 30,8% (Intervalo de confianza al 95%, de 25,1) y una especificidad del 99,4±0,8. Hay que considerar la eventual influencia en los resultados aportada por la posible aparición de dos falsos negativos en el cultivo.Se encuentra un elevado porcentaje de muestras correspondientes a Legionella pneumophilla serogrupo 1, dentro de estas prevalecen las tipo Pontiac Philadelphia, y dentro de estas las tipo Lugano.La primera desinfección no erradicó la contaminación en su totalidad. Abundando en lo anterior, el hallazgo de un número considerable de torres de refrigeración positivas a Lp tras limpieza y desinfección, con cultivos previos negativos redunda en la variabilidad de los resultados analíticos y/o en la ineficacia de las primeras limpiezas y desinfecciones realizadas por empresas.Lo expuesto anteriormente unido a la baja sensibilidad de la PCR deben de ser tenidos en cuenta en futuros incidentes

A novel Carcinoembryonic Antigen (CEA)-Targeted Trimeric Immunotoxin shows signifcantly enhanced Antitumor Activity in Human Colorectal Cancer Xenografts

Immunotoxins are chimeric molecules, which combine antibody specifcity to recognize and bind with high-afnity tumor-associated antigens (TAA) with the potency of the enzymatic activity of a toxin, in order to induce the death of target cells. Current immunotoxins present some limitations for cancer therapy, driving the need to develop new prototypes with optimized properties. Herein we describe the production, purifcation and characterization of two new immunotoxins based on the gene fusion of the anti-carcinoembryonic antigen (CEA) single-chain variable fragment (scFv) antibody MFE23 to α-sarcin, a potent fungal ribotoxin. One construct corresponds to a conventional monomeric single-chain immunotoxin design (IMTXCEAαS), while the other one takes advantage of the trimerbody technology and exhibits a novel trimeric format (IMTXTRICEAαS) with enhanced properties compared with their monomeric counterparts, including size, functional afnity and biodistribution, which endow them with an improved tumor targeting capacity. Our results show the highly specifc cytotoxic activity of both immunotoxins in vitro, which was enhanced in the trimeric format compared to the monomeric version. Moreover, the trimeric immunotoxin also exhibited superior antitumor activity in vivo in mice bearing human colorectal cancer xenografts. Therefore, trimeric immunotoxins represent a further step in the development of next-generation therapeutic immunotoxins

Genetic Effects on Transcriptome Profiles in Colon Epithelium Provide Functional Insights for Genetic Risk Loci

Background & aims: The association of genetic variation with tissue-specific gene expression and alternative splicing guides functional characterization of complex trait-associated loci and may suggest novel genes implicated in disease. Here, our aims were as follows: (1) to generate reference profiles of colon mucosa gene expression and alternative splicing and compare them across colon subsites (ascending, transverse, and descending), (2) to identify expression and splicing quantitative trait loci (QTLs), (3) to find traits for which identified QTLs contribute to single-nucleotide polymorphism (SNP)-based heritability, (4) to propose candidate effector genes, and (5) to provide a web-based visualization resource. Methods: We collected colonic mucosal biopsy specimens from 485 healthy adults and performed bulk RNA sequencing. We performed genome-wide SNP genotyping from blood leukocytes. Statistical approaches and bioinformatics software were used for QTL identification and downstream analyses. Results: We provided a complete quantification of gene expression and alternative splicing across colon subsites and described their differences. We identified thousands of expression and splicing QTLs and defined their enrichment at genome-wide regulatory regions. We found that part of the SNP-based heritability of diseases affecting colon tissue, such as colorectal cancer and inflammatory bowel disease, but also of diseases affecting other tissues, such as psychiatric conditions, can be explained by the identified QTLs. We provided candidate effector genes for multiple phenotypes. Finally, we provided the Colon Transcriptome Explorer web application. Conclusions: We provide a large characterization of gene expression and splicing across colon subsites. Our findings provide greater etiologic insight into complex traits and diseases influenced by transcriptomic changes in colon tissue

Booster effect after SARS-CoV-2 vaccination in immunocompromised hematology patients with prior COVID-19

Patients with hematological malignancies have been excluded from the new zoonotic coronavirus (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) vaccine trials despite being at higher risk for SARS-CoV-2 disease (COVID-19)-related mortality. However, most health authorities worldwide have designated these patients as a priority for COVID-19 vaccination, even in the absence of efficacy data in these highly immunosuppressed patients. In addition, on 12 August 2021, the US Food and Drug Administration amended the emergency use authorizations for the Pfizer-BioNTech and Moderna COVID-19 vaccines to allow for the use of an additional dose in immunocompromised individuals, such as solid organ transplant recipients or equivalently immunosuppressed patients