Vectorization of ultrasound-responsive nanoparticles in placental mesenchymal stem cells for cancer therapy

A new platform constituted by engineered responsive nanoparticles transported by human mesenchymal stem cells is here presented as a proof of concept. Ultrasound-responsive mesoporous silica nanoparticles are coated with polyethylenimine to favor their effective uptake by decidua-derived mesenchymal stem cells. The responsive-release ability of the designed nanoparticles is confirmed, both in vial and in vivo. In addition, this capability is maintained inside the cells used as carriers. The migration capacity of the nanoparticle-cell platform towards mammary tumors is assessed in vitro. The efficacy of this platform for anticancer therapy is shown against mammary tumor cells by inducing the release of doxorubicin only when the cell vehicles are exposed to ultrasound

Transcranial static magnetic stimulation reduces seizures in a mouse model of Dravet syndrome

Dravet syndrome is a rare form of severe genetic epilepsy characterized by recurrent and long-lasting seizures. It appears around the first year of life, with a quick evolution toward an increase in the frequency of the seizures, accompanied by a delay in motor and cognitive development, and does not respond well to antiepileptic medication. Most patients carry a mutation in the gene SCN1A encoding the α subunit of the voltage-gated sodium channel Nav1.1, resulting in hyperexcitability of neural circuits and seizure onset. In this work, we applied transcranial static magnetic stimulation (tSMS), a non-invasive, safe, easy-to-use and affordable neuromodulatory tool that reduces neural excitability in a mouse model of Dravet syndrome. We demonstrate that tSMS dramatically reduced the number of crises. Furthermore, crises recorded in the presence of the tSMS were shorter and less intense than in the sham condition. Since tSMS has demonstrated its efficacy at reducing cortical excitability in humans without showing unwanted side effects, in an attempt to anticipate a possible use of tSMS for Dravet Syndrome patients, we performed a numerical simulation in which the magnetic field generated by the magnet was modeled to estimate the magnetic field intensity reached in the cerebral cortex, which could help to design stimulation strategies in these patients. Our results provide a proof of concept for nonpharmacological treatment of Dravet syndrome, which opens the door to the design of new protocols for treatmentXunta de Galicia | Ref. ED431C 2022/05 (CR)Instituto de Salud Carlos III | Ref. PI16/00425Agencia Estatal de Investigación | Ref. PID2019-108250RJ-100Agencia Estatal de Investigación | Ref. RYC2019–026380-

Optical Spectra of SNR Candidates in NGC 300

We present moderate-resolution (<5A) long-slit optical spectra of 51 nebular objects in the nearby Sculptor Group galaxy NGC 300 obtained with the 2.3 meter Advanced Technology Telescope at Siding Spring Observatory, Australia. Adopting the criterion of [SII]/Ha>=0.4 to confirm supernova remnants (SNRs) from optical spectra, we find that of 28 objects previously proposed as SNRs from optical observations, 22 meet this criterion with six showing [SII]/Ha of less than 0.4. Of 27 objects suggested as SNRs from radio data, four are associated with the 28 previously proposed SNRs. Of these four, three (included in the 22 above) meet the criterion. In all, 22 of the 51 nebular objects meet the [SII]/Ha criterion as SNRs while the nature of the remaining 29 objects remains undetermined by these observations.Comment: Accepted for publication in Astrophysics & Space Scienc

Indoor-outdoor NOX modelling in a single-side naturally ventilated room in a real building in Madrid

The specific objectives of this work are to assess a Computational Fluid Dynamics (CFD) modelling performance through data of one experimental campaign, to quantify the impact of outdoor NOX traffic emissions on indoor NOX concentration and to investigate the natural ventilation using the infiltrated NOX concentration decay and the Air Changes per Hour (ACHs). For this purpose, NOX transport phenomena in a single-side naturally ventilated room in a real building in Madrid is investigated through an Unsteady Reynolds-Averaged Navier-Stokes (URANS) approach and individual passive scalar transport equations for each source (parked vehicles with the engine idling, street traffic and urban background). The combination of this methodology with suitable boundary conditions properly reproduces the time evolution of Wind Speed (WS), Wind Direction (WD) and Turbulent Kinetic Energy (κ), both inside the streets and above the buildings, even for WS < 1 m s−1, and also outdoor and indoor NOX concentrations. In this case, urban background significantly contributes to the indoor concentration and idling vehicles just below the room can contribute between 10 % and 50 % to the total indoor concentration, even when their emissions are considerably smaller than those of traffic in nearby streets. The Indoor-Outdoor NOX concentration ratio (I/O) depends not only on the outdoor concentration (which, at the same time, depends on the atmospheric turbulence) but also on the ventilation (in this case, type Single-Sided Ventilation, SSV), showing a wide range of values. The impact of an indoor Heat Source (HS) below the open window on I/O is low, but under certain meteorological conditions, the stack pressure could be more important than the wind pressure. The time required to ventilate the room is 3.4 min. It has been obtained using the infiltrated NOX concentration decay and has been verified through the average ACH, ⟨ACH(t)⟩. These results provide a better understanding of the impact of the meteorological conditions in outdoor-indoor NOX exchange by natural ventilation, which is the main goal of this research

Spatio-temporal trends of the bottom trawling activity in a mud volcano field of the north-eastern Gulf of Cádiz (south-western Iberian Peninsula)

Multi-species bottom trawl fisheries are one of the human activities with a great impact on the benthic habitats and their associated biota. This study provides estimates of the bottom trawling activity (effort), catches and landings of the main commercial species as well as an estimation of the total revenue (TR) generated inside a mud volcano field located in the Spanish margin of the Gulf of Cádiz, during a time series from 2007 to 2012. To date, no studies have been carried out to analyse the temporal evolution of bottom trawling activity and TR in a mud volcano fied, or the economic consequences of possible potential bottom trawling regulation of certain sectors harbouring vulnerable and/or threatened habitats. In this study, Vessel Monitoring System data, logbooks and sales slips were used. The spatial distribution of the bottom trawling activity, catches and TR were related to the seafloor morphology and specific bottom types of the mud volcano field. During the time series, a high bottom trawling activity and associated catches was detected in flat sandy and muddy bottoms, including the Anastasya sector and between the Guadalquivir and Cádiz Diapiric Ridges. Low bottom trawling activity and catches were detected in the deepest areas but also in areas with hard and detritic bottoms such as Gazul and Chica sectors as well as in the Diapiric Ridges. A similar spatial pattern was detected for the TR asociated with these bottom trawling fisheries. An increase in bottom trawling activity was detected during the time series, mainly at the end, probably for increasing the TR and mantaining the economic profit due to the instability and increases in fuel prices and offset the increased costs. Based on the obtained information, bottom trawling regulations should be implemented in certain sectors harboring singular and/or threatened habitats and species. In some of these sectors, a low TR from bottom trawling was detected and, bottom trawling regulation may potentially have a low socioeconomic impact. This specific bottom trawling regulation could provide a sustainable balance between bottom trawling activities and habitat conservation in this mud volcano field according to the aims of the Habitats Directive (92/43/EEC) and the European Marine Strategy Framework Directive (2008/56/EEC).En prens

Native vs photoinduced chemiluminescence in dimethoate determination

The determination of dimethoate using either its native chemiluminescent (CL) properties or its photoinduced chemiluminescence obtained by irradiation with a 15W low-pressure mercury lamp was studied. Thereby, two flow injection systems (FIA) with and without irradiation were exhaustively optimized and their analytical characteristics studied. Better sensitivity and selectivity was found in absence of irradiation, due to the enhancing effect of hexadecylpyridinium chloride (HPC), which acted as a sensitizer. In the developed FIA-CL system, the alkaline hydrolysis of dimethoate with NaOH was performed on-line in presence of HPC. The oxidation of the product of hydrolysis with Ce(IV) in hydrochloric medium induced chemiluminescence. The method provided a limit of detection of only 0.05ngmL -1 without any pre-treatment. However, the combination with solid phase extraction allowed the removal of some potential interferents as well as the preconcentration of the pesticide. Finally, the developed method was successfully applied to natural waters with recoveries between 95 and 108%. © 2011 Elsevier B.V.This work was supported by the Ministry of Education and Science of Spain (Project CTM2006-11991) and FEDER funds.Catalá Icardo, M.; López Paz, JL.; Choves Barón, C.; Pena Badena, A. (2012). Native vs photoinduced chemiluminescence in dimethoate determination. ANALYTICA CHIMICA ACTA. 710:81-87. https://doi.org/10.1016/j.aca.2011.10.043S818771

High prognostic value of measurable residual disease detection by flow cytometry in chronic lymphocytic leukemia patients treated with front-line fludarabine, cyclophosphamide, and rituximab, followed by three years of rituximab maintenance

It has been postulated that monitoring measurable residual disease (MRD) could be used as a surrogate marker of progression-free survival (PFS) in chronic lymphocytic leukemia (CLL) patients after treatment with immunochemotherapy regimens. In this study, we analyzed the outcome of 84 patients at 3 years of follow-up after first-line treatment with fludarabine, cyclophosphamide and rituximab (FCR) induction followed by 36 months of rituximab maintenance thearpy. MRD was assessed by a quantitative four-color flow cytometry panel with a sensitivity level of 10-4. Eighty out of 84 evaluable patients (95.2%) achieved at least a partial response or better at the end of induction. After clinical evaluation, 74 patients went into rituximab maintenance and the primary endpoint was assessed in the final analysis at 3 years of follow-up. Bone marrow (BM) MRD analysis was performed after the last planned induction course and every 6 months in cases with detectable residual disease during the 36 months of maintenance therapy. Thirty-seven patients (44%) did not have detectable residual disease in the BM prior to maintenance therapy. Interestingly, 29 patients with detectable residual disease in the BM after induction no longer had detectable disease in the BM following maintenance therapy. After a median followup of 6.30 years, the median overall survival (OS) and PFS had not been reached in patients with either undetectable or detectable residual disease in the BM, who had achieved a complete response at the time of starting maintenance therapy. Interestingly, univariate analysis showed that after rituximab maintenance OS was not affected by IGHV status (mutated vs. unmutated OS: 85.7% alive at 7.2 years vs. 79.6% alive at 7.3 years, respectively). As per protocol, 15 patients (17.8%), who achieved a complete response and undetectable peripheral blood and BM residual disease after four courses of induction, were allowed to stop fludarabine and cyclophosphamide and complete two additional courses of rituximab and continue with maintenance therapy for 18 cycles. Surprisingly, the outcome in this population was similar to that observed in patients who received the full six cycles of the induction regimen. These data show that, compared to historic controls, patients treated with FCR followed by rituximab maintenance have high-quality responses with fewer relapses and improved OS. The tolerability of this regime is favorable. Furthermore, attaining an early undetectable residual disease status could shorten the duration of chemoimmunotherapy, reducing toxicities and preventing long-term side effects. The analysis of BM MRD after fludarabine-based induction could be a powerful predictor of post-maintenance outcomes in patients with CLL undergoing rituximab maintenance and could be a valuable tool to identify patients at high risk of relapse, influencing further treatment strategies

San José: Desde Las Negras a Cabo de Gata (Almería). Serie B: Gestión.

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