Immune thrombotic thrombocytopenic purpura in older patients: Results from the Spanish TTP Registry (REPTT).

Immune thrombotic thrombocytopenic purpura (iTTP) is an ultra-rare disease that seldom occurs in the elderly. Few reports have studied the clinical course of iTTP in older patients. In this study, we have analysed the clinical characteristics at presentation and response to therapy in a series of 44 patients with iTTP ≥60 years at diagnosis from the Spanish TTP Registry and compared them with 209 patients with <60 years at diagnosis from the same Registry. Similar symptoms and laboratory results were described in both groups, except for a higher incidence of renal dysfunction among older patients (23% vs. 43.1%; p = 0.008). Front-line treatment in patients ≥60 years was like that administered in younger patients. Also, no evidence of a difference in clinical response and overall survival was seen in both groups. Of note, 14 and 25 patients ≥60 years received treatment with caplacizumab and rituximab, respectively, showing a favourable safety and efficacy profile, like that observed in patients <60 years.

A strategic reflection for the management and implementation of CAR-T therapy in Spain: an expert consensus paper

CAR-T cell therapy represents a therapeutic revolution in the prognosis and treatment of patients with certain types of hematological cancer. However, they also pose new challenges in the healthcare, regulatory and financial fields. The aim of the RET-A project was to undertake a strategic reflection on the management of CAR-T therapies within the Spanish National Health System, to agree on recommendations that will help to better deal with the new context introduced by these cell therapies in the present and in the future. This think tank involved 40 key agents and opinion leaders. The experts identified three great challenges for implementing advanced therapies in Spain: therapeutic individualisation, with a multidisciplinary approach; acceleration of access times, by minimizing bureaucracy; and increase in the number of centers qualified to manage the CAR-T therapies in the NHS. The experts agreed on the ideal criteria for designating those qualified centers. They also agreed on a comprehensive CAR-T care pathway with the timings and roles which would ideally be involved in each part of the process.

A strategic reflection for the management and implementation of CAR-T therapy in Spain: an expert consensus paper.

CAR-T cell therapy represents a therapeutic revolution in the prognosis and treatment of patients with certain types of hematological cancer. However, they also pose new challenges in the healthcare, regulatory and financial fields. The aim of the RET-A project was to undertake a strategic reflection on the management of CAR-T therapies within the Spanish National Health System, to agree on recommendations that will help to better deal with the new context introduced by these cell therapies in the present and in the future. This think tank involved 40 key agents and opinion leaders. The experts identified three great challenges for implementing advanced therapies in Spain: therapeutic individualisation, with a multidisciplinary approach; acceleration of access times, by minimizing bureaucracy; and increase in the number of centers qualified to manage the CAR-T therapies in the NHS. The experts agreed on the ideal criteria for designating those qualified centers. They also agreed on a comprehensive CAR-T care pathway with the timings and roles which would ideally be involved in each part of the process.

Medidas de control de la transmisión de infecciones en el entorno quirúrgico: cambio de paradigma tras la COVID-19 / Measures for prevention of infection transmission in the operating room: Paradigm shift after COVID-19

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Fabrication of a multifunctional magnetic-fluorescent material for medical applications.

Multifunctional biocompatible materials have evoked considerable interest in the field of medical applications. Here we report the thermal decomposition preparation of homogeneous fluorescent-magnetic particles with a composite structure containing CoFe2O4 nanoparticles as nucleation seeds for fluorescent Gd2-xO3:Eux. The composite exhibited a wide range of fluorescence transitions in the whole visible spectrum, displaying 18 different emission peaks when excited at a 250 nm wavelength. Moreover, at low temperature the peaks of the composite were wider than the peaks of the fluorescent material, which may be attributed to a set of new energy levels due to a combination of Stark splitting with the magnetic field of CoFe2O4. Because this material is intended to be used for biomedical applications, the potential toxicity of the composite was tested using an invertebrate hemocyte cell model. The cells showed slight morphological and biochemical changes upon exposure to the composite; however, there was no increase in cell death at concentrations of up to 40 ppm. In addition, the material could be tracked by its fluorescence inside the cells, when excited at a more bio-friendly and less energetic wavelength of 405 nm. Furthermore, MRI showed T1 and T2 dual contrast with relaxivity values in the range of most reported materials.

Caracterización de materiales (pigmentos y cerámicas) para la conservación del patrimonio cultural y social en ciudad de La Habana / Characterization of materials (pigments and ceramics) for the conservation of cultural and social heritage in the city of Havana

RESUMEN Una de las direcciones de aplicación de la Ciencia de Materiales que realiza el Centro de Aplicaciones Tecnológicas y Desarrollo Nuclear CEADEN es el apoyo mediante un grupo de técnicas físicas a la restauración y el mantenimiento de estructuras y objetos de la ciudad de La Habana, entre otras localidades de Cuba, que poseen interés artístico y social . En el presente trabajo se abordan varias aplicaciones en la caracterización de materiales para contribuir a las actividades de conservación del patrimonio cultural e histórico cubano que se encuentra en La Habana. Se presentan dos ejemplos de análisis por las técnicas de Fluorescencia de Rayos X y Difracción de rayos X de los pigmentos de obras en lienzos y de la paleta de una reconocida artista de la plástica cubana; así como el de tejas cerámicas que fueron utilizadas en la restauración de los techos de la residencia conocida como Casa Verde de 5ta Avenida en el Municipio Playa.

ABSTRACT One of the applications in Materials Science carried out at the Center for Technological Applications and Nuclear Development (CEADEN) is the technical support through several methods used, based on applied Physics for the restoration and maintenance of structures and objects holding artistic and social relevance in Havana city. The aim of this paper is to present two examples of X -ray Fluorescence and Diffraction materials characterization, intended to support conservation and restoration activities of the Cuban cultural and historic heritage: analyzed objects were pottery roof tiles for the restoration of the mansion known as The Green House at 5th Avenue, Miramar, as well as pigments from a Cuban fine artist's canvas and palette.

Multifractal analysis to study break points in temperature data sets.

Since the last century, the air surface temperature has increased at a global scale, showing trends and inhomogeneities that vary from place to place. Many statistical methods can be used to analyze whether or not an inhomogeneity or break point exists in a meteorological data series, and even to detect the time of the break. Sometimes, there is no agreement in the year at which the inhomogeneity occurs detected by different tests. The scale invariance of a process can be studied through its multifractal properties that can be related to the existence of break points in it. In this work, the multifractal properties of monthly temperature data series are used to test what is the right break point year in those situations at which different dates are found by two different tests: the Pettitt and the Standard Normal Homogeneity tests. The comparison of the fractal dimension function Dq and the multifractal spectrum obtained by the box counting method for both the original data sets and for those obtained by splitting the original into two considering the break point years was made. When different multifractal functions and parameters were obtained, a break point was confirmed. Whereas, if equal values appeared, the break point year was discarded. These results let to select the most suitable test to be applied to detect inhomogeneities in a certain data set that will be very useful for climate change studies.

Multifractal analysis of diurnal temperature range over Southern Spain using validated datasets.

Multifractal properties of diurnal temperature range (DTR) have been analyzed in this work, using validated data of maximum and minimum temperature from 197 weather stations in Southern Spain (Andalusia region). DTR is a crucial factor to characterize the regional climate, providing more information than the average daily temperature. Apart from climate change studies, one of the most important applications of DTR in Agrometeorology is as an input variable in the solar radiation or reference evapotranspiration estimation models based on the temperature. With the aim of obtaining a detailed information for different time scales, different multifractal approaches have been applied. Different quality control methods such as range/limits or persistence tests were previously applied in order to detect incorrect and anomalous values, being discarded in the subsequent analysis. The DTR scaling of moments has been analyzed and the moment scaling exponent function K(q) has been obtained, finding some differences between weather stations. In addition, multifractal dimension (D1) and multifractal degree (MD) were also estimated, revealing differences at coastal and inland locations that show heterogeneity across the region, including its multifractal nature and its invariance for a range of scales. The nonlinear characterization carried out in this work improves the understanding of DTR as an indicator of climate changes, and it can have a very positive impact on the calibration of regional models for estimating solar radiation or reference evapotranspiration based on the temperature. This multifractal characterization can be used to group stations with similar nonlinear dynamics, regardless of their geographical features, in such a way that more accurate coefficients than conventional ones are used.

[Microscopic peritoneal metastases of epithelial ovarian cancers. Clinical relevance, diagnostic and therapeutic tools]. / Métastases péritonéales microscopiques des cancers épithéliaux de l'ovaire. Pertinence clinique, outils diagnostiques et thérapeutiques.

Understanding the biology and progression mechanisms of peritoneal metastases in ovarian epithelial cancers (EOC) is important because peritoneal carcinomatosis is present or will occur during surveillance of a majority of patients. Despite the clinical remission achieved after complete macroscopic cytoreductive surgery and platinum-based chemotherapy, 60% of patients will develop peritoneal recurrence. This suggests that microscopic lesions, which are not eradicated by surgery may be present and may participate in the mechanisms leading to peritoneal recurrence. This paper discusses current available data on microscopic peritoneal metastases, their diagnosis and their treatment. We reviewed all publications dealing with microscopic peritoneal metastases of EOC between 1980 and 2017. The most recent and most relevant publications dealing with the treatment modalities of these metastases were selected. Peritoneal and epiploic microscopic localizations would occur in 1.2 to 15.1% of cases at early-stage and are not treated during conventional surgery. They could represent a potential therapeutic target. Local treatments (intraperitoneal chemotherapy, photodynamic therapy, fluorescence-guided surgery) seem to be necessary in addition to surgery and chemotherapy and may help reduce the risk of peritoneal recurrence. The place of these treatments in the management of EOC remains to be defined by subsequent researches.

Anaerobic digestion of cheese whey: Energetic and nutritional potential for the dairy sector in developing countries.

Cheese whey (CW) is the main waste generated in the cheesemaking process and has high organic matter content and acidity. Therefore, CW disposal is a challenge for small to medium enterprises (SMEs) in the dairy industry that do not have any type of treatment plant. Anaerobic digestion (AD) is an attractive process for solving this problem. The aim of this research was to determine the biomethane and struvite precipitation potentials of CW from four dairy SMEs. First, changes in CW properties (organic matter and pH) were evaluated. Second, biomethane and struvite potentials were assessed using cattle slurry as inoculum. The organic matter in CW varied from 40 to 65gVS/kg, 65 to 140g COD/L, and 2 to 10g/L for VFAs depending on the sampling time and type of sample. The pH of the CW samples ranged from 3 to 6.5. In the anaerobic biodegradability analysis, methane yields reached 0.51 to 0.60L CH4/g VSadded, which represented electrical and caloric potentials of 54 and 108kWh/m3 for CW, respectively. Organic matter removal in all experiments was above 83%. Moreover, anaerobic digestates presented NH4+/PO43- molar ratios between 2.6 and 4.0, which are adequate for struvite precipitation with potential production of 8.5-10.4g struvite/L CW. Finally, the use of biogas as energetic supplement and struvite as soil fertilizer, represents economics saves of US$ 6.91/m3 CW and US$ 5.75/m3 CW in therms of electricity and fertilizer use, respectively. The energetic, agricultural and economic potentials, evidence that AD process is a feasible alternative for cheese whey treatment.

Differential effects of exposure to parasites and bacteria on stress response in turbot Scophthalmus maximus simultaneously stressed by low water depth.

The stress response of turbot Scophthalmus maximus was evaluated in fish maintained 8 days under different water depths, normal (NWD, 30 cm depth, total water volume 40 l) or low (LWD, 5 cm depth, total water volume 10 l), in the additional presence of infection-infestation of two pathogens of this species. This was caused by intraperitoneal injection of sublethal doses of the bacterium Aeromonas salmonicida subsp. salmonicida or the parasite Philasterides dicentrarchi (Ciliophora:Scuticociliatida). The LWD conditions were stressful for fish, causing increased levels of cortisol in plasma, decreased levels of glycogen in liver and nicotinamide adenine dinucleotide phosphate (NADP) and increased activities of G6Pase and GSase. The presence of bacteria or parasites in fish under NWD resulted in increased cortisol levels in plasma whereas in liver, changes were of minor importance including decreased levels of lactate and GSase activity. The simultaneous presence of bacteria and parasites in fish under NWD resulted a sharp increase in the levels of cortisol in plasma and decreased levels of glucose. Decreased levels of glycogen and lactate and activities of GSase and glutathione reductase (GR), as well as increased activities of glucose-6-phosphate dehydrogenase (G6PDH), 6-phosphogluconate dehydrogenase (6PGDH) and levels of nicotinamide adenine dinucleotide phosphate (NADPH) occurred in the same fish in liver. Finally, the presence of pathogens in S. maximus under stressful conditions elicited by LWD resulted in synergistic actions of both type of stressors in cortisol levels. In liver, the presence of bacteria or parasites induced a synergistic action on several variables such as decreased activities of G6Pase and GSase as well as increased levels of NADP and NADPH and increased activities of GPase, G6PDH and 6PGDH.

Low cost digester monitoring under realistic conditions: Rural use of biogas and digestate quality.

The purpose of this work was to assess the behaviour of anaerobic digestion of cattle manure in a rural digester under realistic conditions, and estimate the quality and properties of the digestate. The data obtained during monitoring indicated that the digester operation was stable without risk of inhibition. It produced an average of 0.85Nm3biogas/d at 65.6% methane, providing an energy savings of 76%. In addition, the digestate contained high nutrient concentrations, which is an important feature of fertilizers. However, this method requires post-treatment due to the presence of pathogens.

Room Temperature Crystallization of Hydroxyapatite in Porous Silicon Structures.

Porous silicon (PS) substrates, with different pore sizes and morphology, have been used to crystallize hydroxyapatite (HA) nano-fibers by an easy and economical procedure using a co-precipitation method at room temperature. In situ formation of HA nanoparticles, within the meso- and macroporous silicon structure, resulted in the formation of nanometer-sized hydroxyapatite crystals on/within the porous structure. The X-ray diffraction technique was used to determine the tetragonal structure of the crystals. Analysis/characterization demonstrates that under certain synthesis conditions, growth and crystallization of hydroxyapatite layer on/inside PS can be achieved at room temperature. Such composite structures expand the possibility of designing a new bio-composite material based on the hydroxyapatite and silicon synthesized at room temperature.

[Current controversies regarding power morcellation and future directions]. / Morcellement utérin : controverses actuelles et futurs développements.

Modern surgery tends to the improvement of minimally invasive strategies. Laparoscopy, rooted in practices for years, supplanted laparotomy in many directions. Regarding the extraction of large uterus, morcellation is currently the only way to externalize surgical specimens (myomas, uterine), without increasing the skin opening while allowing to reduce postoperative complications compared to laparotomy. However, in 2014, the Food and Drug Administration (FDA) discourages the use of uterine morcellation because of oncological risk. This recommendation has been challenged by a part of the profession. Our review has sought to identify the evidence for and against the use of morcellation. We also tried to quantify surgical risk and the current means of prevention. The incidence of uterine sarcomas is still poorly identified and preoperative diagnostic facilities remain inadequate. The small number of retrospective studies currently available could not enable any recommendation. The evaluation of morcellation devices and the improvement of preoperative diagnosis modalities (imaging, preoperative biopsy) are to continue to minimize the oncological risk.

Pharmacokinetics and preliminary efficacy of two vaginal gel formulations of ultra-low-dose estriol in postmenopausal women.

OBJECTIVES: To investigate the pharmacokinetics, safety and preliminary effectiveness of ultra-low-dose estriol vaginal gel formulations (20 µg/g (T1) and 50 µg/g (T2)) compared to Ovestinon® (estriol 500 µg/0.5 g (R)) and placebo in postmenopausal women. METHODS: Forty-three volunteers were randomly assigned to received T1, T2, R or placebo once daily for 21 days. Absorption of estriol after single and multiple administration was analyzed. Cytological changes in the vagina, tolerability and safety were also investigated. RESULTS: Thirty-six women were included in the pharmacokinetic analysis. Systemic absorption was lower with test formulations (AUC0-t: 171.65 ± 80.18 (T1) and 406.75 ± 199.53 (T2) pg/ml × h) than with Ovestinon® (1221.97 ± 549.06 pg/ml × h). Estriol exposure of the test formulations after multiple administration (AUCss: 36.33 ± 30.52 (T1) and 73.71 ± 46.86 (T2) pg/ml × h) was significantly lower than after single-dose administration and not significantly different between them. In contrast, the exposure after repeated administration of Ovestinon® was considerable and not statistically different from levels after single administration. All estriol formulations produced similar improvement in the vaginal maturation value, while placebo showed a small and not significant change. Overall safety and acceptability were good. CONCLUSIONS: Estriol 20 and 50 µg/g formulations, while showing a comparable capacity for reversing vaginal atrophy, present a highly favorable safety profile, producing a very low systemic absorption of estriol and significantly lower than that of Ovestinon®.

Encystment/excystment response and serotypic variation in the gastropod parasite Tetrahymena rostrata (Ciliophora, Tetrahymenidae).

Tetrahymena rostrata, which is characterized by a particular encystment-excystment cycle involving autogamy, has been recently found infecting the kidney of edible Helix aspersa snails under farming conditions. In this work, the effects of several factors on its encystment/excystment behaviour and the occurrence of different serotypes were investigated. The encystment/excystment response under starvation conditions was seriously affected by temperature. While a peak of encystment at 48 h followed by a progressive spontaneous excystment was observed at 18 and 25 °C, the encystment response was practically inhibited at 5 °C and clearly slowed down at 10 °C. At 30 °C, most of surviving ciliates remained encysted throughout the experiment, with spontaneous excystment being detected only after switching the temperature to 18 °C. Soil components also affected the encystment/excystment behaviour at 18 °C, with spontaneous excystment occurring in the presence of a sterile-filtered soil extract or mineral water but being strongly minimized with a non-filtered soil extract. Resting cysts formed in the latter extract exhibited a 3­4 times thicker and ultrastructurally more complex wall than that formed in mineral water and retained the excystment ability for about 4 weeks. Incomplete desiccation did not affect significantly the encystment response, while the mucus and kidney extracts from snails as well as a ciliate extract strongly stimulated a rapid excystment. Finally, two different serotypes infecting H. aspersa in heliciculture farms of Galicia (NW Spain) were identified, but no differences were observed between the encystment/excystment responses exhibited by two isolates belonging to each serotype.

Resolving pathways of interaction of mipafox and a sarin analog with human acetylcholinesterase by kinetics, mass spectrometry and molecular modeling approaches.

The hydroxyl oxygen of the catalytic triad serine in the active center of serine hydrolase acetylcholinesterase (AChE) attacks organophosphorus compounds (OPs) at the phosphorus atom to displace the primary leaving group and to form a covalent bond. Inhibited AChE can be reactivated by cleavage of the Ser-phosphorus bond either spontaneously or through a reaction with nucleophilic agents, such as oximes. At the same time, the inhibited AChE adduct can lose part of the molecule by progressive dealkylation over time in a process called aging. Reactivation of the aged enzyme has not yet been demonstrated. Here, our goal was to study oxime reactivation and aging reactions of human AChE inhibited by mipafox or a sarin analog (Flu-MPs, fluorescent methylphosphonate). Progressive reactivation was observed after Flu-MPs inhibition using oxime 2-PAM. However, no reactivation was observed after mipafox inhibition with 2-PAM or the more potent oximes used. A peptide fingerprinted mass spectrometry (MS) method, which clearly distinguished the peptide with the active serine (active center peptide, ACP) of the human AChE adducted with OPs, was developed by MALDI-TOF and MALDI-TOF/TOF. The ACP was detected with a diethyl-phosphorylated adduct after paraoxon inhibition, and with an isopropylmethyl-phosphonylated and a methyl-phosphonylated adduct after Flu-MPs inhibition and subsequent aging. Nevertheless, nonaged nonreactivated complexes were seen after mipafox inhibition and incubation with oximes, where MS data showed an ACP with an NN diisopropyl phosphoryl adduct. The kinetic experiments showed no reactivation of activity. The computational molecular model analysis of the mipafox-inhibited hAChE plots of energy versus distance between the atoms separated by dealkylation showed a high energy demand, thus little aging probability. However, with Flu-MPs and DFP, where aging was observed in our MS data and in previously published crystal structures, the energy demand calculated in modeling was lower and, consequently, aging appeared as a more likely reaction. We document here direct evidence for a phosphorylated hAChE refractory to oxime reactivation, although we observed no aging.