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International audience; Background:Pacemakers (PMs) and implantable cardioverter defibrillators (ICDs) increasingly automatically record and remotely transmit non-sustained ventricular tachycardia (NSVT) episodes which may reveal ventricular oversensing.Objectives:We aimed to develop and validate a machine learning algorithm which accurately classifies NSVT episodes transmitted by PMs and ICDs in order to lighten healthcare workload burden and improve patient safety.Methods:PMs or ICDs (Boston Scientific) from four French hospitals with ≥1 transmitted NSVT episode were split into three subgroups: training set, validation set, and test set. Each NSVT episode was labelled as either physiological or non-physiological. Four machine learning algorithms (2DTF-CNN, 2D-DenseNet, 2DTF-VGG, and 1D-AgResNet) were developed using a training and validation dataset. Accuracies of the classifiers were compared with an analysis of the remote monitoring team of the Bordeaux University Hospital using F2 scores (favoring sensitivity over predictive positive value) using an independent test set.Results:807 devices transmitted 10.471 NSVT recordings (82% ICD, 18% PM), of which 87 devices (10.8%) transmitted 544 NSVT recordings with non-physiological signals. The classification by the remote monitoring team resulted in an F2 score of 0,932 (sensitivity of 95%, specificity of 99%) The four machine learning algorithms showed high and comparable F2 scores (2DTF-CNN: 0,914, 2D-DenseNet: 0,906, 2DTF-VGG: 0,863, 1D-AgResNet: 0,791) and only 1D-AgResNet had significantly different labeling as compared with the remote monitoring team.Conclusion:Machine learning algorithms were accurate in detecting non-physiological signals within EGMs transmitted by pacemaker and ICDs. An artificial intelligence approach may render remote monitoring less resourceful and improve patient safety.

In the few last years, a new family of drugs, anti-calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs), has been developed for migraine therapy. Anti-CGRP mAbs are highly effective, but the current limited experience with their use and their high-cost warrant establishing certain rules of use.The present review provides an overview of the management of migraine patients, especially those who are undergoing treatment with anti-CGRP mAbs.Thanks to new research focused on the pathophysiology of migraine, and the discovery that CGRP plays a key role in its etiopathogenesis, new drugs targeting CGRP have been developed. These drugs have led to a paradigm shift, anticipating new and stimulating possibilities in migraine treatment. While physicians and patients are full of expectation about the advantages of this new family of drugs, there are still obstacles to overcome in order to make the best use of them. It is essential to form multidisciplinary teams that can identify patients who will benefit from these therapies, conducting cost-effective treatments. The follow-up of these therapies in the coming years is paramount due to the lack of experience in the management of these drugs and the peculiarity of disease evolution in migraine patients.

Stilbenes are phenolic compounds naturally synthesized as secondary metabolites by the shikimate pathway in plants. Research on them has increased in recent years due to their therapeutic potential as antioxidant, antimicrobial, anti-inflammatory, anticancer, cardioprotective and anti-obesity agents. Amongst them, resveratrol has attracted the most attention, although there are other natural and synthesized stilbenes with enhanced properties. However, stilbenes have some physicochemical and pharmacokinetic problems that need to be overcome before considering their applications. Human clinical evidence of their bioactivity is still controversial due to this fact and hence, exhaustive basis science on stilbenes is needed before applied science. This review gathers the main physicochemical and biological properties of natural stilbenes, establishes structure-activity relationships among them, emphasizing the current problems that limit their applications and presenting some promising approaches to overcome these issues: the encapsulation in different agents and the structural modification to obtain novel stilbenes with better features. The bioactivity of stilbenes should move from promising to evident.

Gnetol is a stilbene whose characterization and bioactivity have been poorly studied. It shares some bioactivities with its analogue resveratrol, such as anti-inflammatory, anti-thrombotic, cardioprotective and anti-cancer activities. However, the low solubility of stilbenes may limit their potential applications in functional foods. Encapsulation in cyclodextrins could be a solution.The antioxidant activity of gnetol was evaluated by 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radical cation and ferric reducing antioxidant power methods (Trolox equivalents 13.48 μmol LThese results could increase interest of gnetol as an alternative to the most studied stilbene, resveratrol, as well as aid in the development of more stable inclusion complexes that improve its aqueous solubility and stability so that it can be incorporated into functional foods. © 2022 The Authors. Journal of The Science of Food and Agriculture published by John WileySons Ltd on behalf of Society of Chemical Industry.

The food industry is constantly attempting to develop better products that will have a positive effect on health. Feiraco® and Clesa®, expressed their intention to create novel products using UNICLA® milk as a matrix to develop functional foods. In this respect, β-cyclodextrin (β-CD) at 1% was able to reduce the cholesterol concentration in Feiraco-UNICLA® milk products by around 87-85%. Products were fortified with omega-3 from fish oil with α- and β-CD acting as carriers. It was possible to add around 50% of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) Recommended Dietary Allowances (RDA), with a high diet proportion of fibre and similar organoleptic properties to commercial omega-3 products. 80% of a sensory panel found our formulations satisfactory. The final product was stable, and the bioaccessibilty of the fatty acids added to the milk was around 74%. These results as a whole satisfy the aid of Feiraco® and Clesa® to develop improved products.

Vitamin D plays an important role in numerous cellular functions due to the ability to bind the Vitamin D receptor (VDR), which is present in different tissues. Several human diseases depend on low vitamin D3 (human isoform) serum level, and supplementation is necessary. However, vitamin D3 has poor bioavailability, and several strategies are tested to increase its absorption. In this work, the complexation of vitamin D3 in Cyclodextrin-based nanosponge (CD-NS, in particular, βNS-CDI 1:4) was carried out to study the possible enhancement of bioactivity. The βNS-CDI 1:4 was synthesized by mechanochemistry, and the complex was confirmed using FTIR-ATR and TGA. TGA demonstrated higher thermostability of the complexed form. Subsequently, in vitro experiments were performed to evaluate the biological activity of Vitamin D3 complexed in the nanosponges on intestinal cells and assess its bioavailability without cytotoxic effect. The Vitamin D3 complexes enhance cellular activity at the intestinal level and improve its bioavailability. In conclusion, this study demonstrates for the first time the ability of CD-NS complexes to improve the chemical and biological function of Vitamin D3.

Entre 2011 y 2014 se desarrolló la gestión municipal del economista Luis Flores García, protagonista de la intervención del Centro Histórico del Cusco. Se destacó por su enfoque social y cultural; no obstante, acciones de revalorización de lo cusqueño, dieron inicio a polémicas en los medios de comunicación; sin embargo, un gran sector de la población lo recuerda con gran cariño porque apoyó el desarrollo de planes urbanos muy demandados. Algunos de sus proyectos, resultaron casi imperceptibles a los vecinos, pero los técnicos advierten que estos mejoraron notablemente la calidad de vida de la ciudadanía, a mediano y largo plazo. El presente artículo analiza dicha gestión y cómo influyó en el barrio tradicional de Santa Ana.

Tesis Doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Medicina, Departamento de Medicina. Fecha de Lectura: 03-11-2022, Natalizumab es un anticuerpo monoclonal (AcMo) muy eficaz en el tratamiento de la esclerosis múltiple remitente recurrente (EMRR), sin embargo, se ha relacionado con el desarrollo de leucoencefalopatía multifocal progresiva (LMP). Está aprobado a una dosis fija en base a los resultados de los estudios pivotales, en los que la concentración media del fármaco en el estado estacionario osciló entre 23 μg/ml y 29 μg/ml, aunque una concentración de entre 1-2 μg/ml es suficiente para lograr la saturación de la integrina α4β1 (su diana de acción). A este hecho hay que añadir que la mayoría de AcMo son dosificados de forma individualizada. Con estos antecedentes, nos propusimos analizar el impacto de diferentes parámetros que incluyen peso, altura, superficie corporal (SC), índice de masa corporal (IMC), edad, género, duración del tratamiento e intervalo de dosis sobre la farmacología de natalizumab, con la hipotesis de que la optimización de las dosis de natalizumab en función de las características individuales de los pacientes, puede garantizar la máxima efectividad del fármaco y reducir al mínimo la posibilidad de aparición de LMP. Para ello, realizamos un estudio prospectivo en el que reclutamos 32 pacientes con EMRR en tratamiento con natalizumab en nuestro hospital desde hacía al menos 7 meses. La farmacocinética se caracterizó midiendo las concentraciones de natalizumab en el suero de los pacientes mediante ensayo inmunoenzimático y la farmacodinamia se estudió midiendo la ocupación del receptor de integrina α4β1 (OR) por citometría de flujo. Las concentraciones detectadas en las muestras fueron muy dispares entre los pacientes (con un rango de entre 0.72 y 67 μg/ml). La mayoría de los pacientes tenían concentraciones de más de 5 μg/ml. El análisis de la OR también reveló gran variabilidad (con un rango de entre 44% a 100%). El peso y el IMC influenciaron de forma significativa tanto la OR como las concentraciones (estas últimas también dependían del esquema de dosis). Por último, se calculó la concentración de natalizumab a la cual la correlación con la OR era máxima, resultando ser de 9 μg/ml. En conclusión, el peso, el IMC y el esquema de tratamiento tienen un impacto significativo sobre la farmacología de natalizumab en cada paciente. Como consecuencia de ello, la mayoría de nuestros pacientes estaban sobretratados, y alguno podría estar infratratado debido a la tendencia clínica actual a utilizar el esquema de dosis extendida. Además, la OR depende en gran medida de la concentración hasta alcanzar 9 μg/ml, a partir de la cual se produce una saturación de los receptores en la mayoría de los pacientes. Nuestros hallazgos sientan las bases para recomendar vivamente la medida de la concentración de natalizumab en suero y de la OR, con el fin de personalizar su esquema de tratamiento y evitar así un uso ineficiente del mismo

Many nutraceuticals present problems due to their poor water solubility or stability, which prevents the final bioactivity achievement. For that reason, the oral administration of KYNA complexed with HPβ-CD and βNS-CDI nanosponges was evaluated in mice. The solvent-free technology was used to prepare the complexes in a complete comparison between kneading in ball milling and classical inclusion complex preparation. The solvent-free ones showed higher strength and efficiency with ball milling, considerably reducing time. A 50 mg KYNA/kg/day dosage was orally administered in formulations showing a higher bioavailability when the nutraceutical was complexed with βNS-CDI compared to HPβ-CD and free KYNA, respectively. Several antioxidant statuses demonstrated a higher global antioxidant level perfectly related to bioavailability. Finally, the formulation of KYNA reduced the temporal oxidative stress damage in the kidney and liver, making βNS-CDI the best formulation. These results suggest an important future application of cyclodextrin-based nanosponges for the oral delivery of nutraceuticals and their stabilization.

Neochlorogenic acid, a less-studied isomer of chlorogenic acid, has been seen to posses antioxidant, antifungal, anti-inflammatory and anticarcinogenic effects, which makes it an interesting candidate for incorporation in functional foods. However, its poor solubility in water and susceptibility to oxidation make such a task difficult. To overcome that, its encapsulation in cyclodextrins (CDs) is proposed. The fluorescence of neochlorogenic acid in different pH conditions was analyzed, and caffeic acid was proved to be the fluorescent moiety in the molecule. An encapsulation model whereby the ligand poses two potential complexation sites (caffeic and D-(-)-quinic moieties), showed that α-CD and HP-β-CD formed the best inclusion complexes with neochlorogenic acid, followed by M-β-CD, β-CD and γ-CD. Molecular docking with the two best CDs gave better scores for α-CD, despite HP-β-CD providing stabilization through H-bonds. The encapsulation of chlorogenic acid led to a similar CD order and scores, although constants were higher for α-CD, β-CD and M-β-CD, lower for HP-β-CD, and negligible for γ-CD. The protonation state affected these results leading to a different order of CD preference. The solubility and the susceptibility to oxidation of neochlorogenic acid improved after complexation with α-CD and HP-β-CD, while the antioxidant activity of both isomers was maintained.

The Fifth Generation (5G) mobile networking coupled with Internet of Things (IoT) can provide innovative solutions for a wide range of uses cases. The flexibility of virtualized, softwarized and multi-tenant infrastructures and the high performance promised by 5G technology are key to cope with the deployment of the IoT use cases demanded by various vertical businesses. Such 5G IoT use cases incur challenging Quality of Service (QoS) requirements especially connectivity for millions of IoT devices to achieve massive Machine-Type Communication (mMTC). In addition, network slicing is a key enabling technology in 5G multi-tenant networks to create logical virtualized networks for delivering customised solutions to meet diverse QoS requirements. This work presents a 5G IoT framework with network slicing capabilities able to manage a vast number of heterogeneous IoT network slices dynamically on demand. The proposed solution has been empirically tested and validated in five realistic vertical-oriented IoT use cases. The achieved results demonstrate a excellent stability, isolation and scalability while being able to meet extreme QoS requirements even in the most congested and stressful scenarios.

In this work, two catalysts, lanthanum manganite strontium-doped perovskite without (LSM) and with (LSMMO) mixed molybdenum oxides, were synthesized by the sol-gel route and deposited by immersion in carbon cloth substrates. Their performance as cathodes in the hydrogen peroxide reduction reaction (HPRR) and oxygen reduction reaction (ORR) was investigated through cyclic voltammetry and electrochemical impedance spectroscopy, the electrocatalytic efficiency of these electrodes in the HPRR was analyzed in KOH and H2O2 medium at 298 K. The performance of the cathodes, in a single compartment, using a nickel plate as an anode was also investigated. The results showed that for the reduction reactions, electrodes developed with LSMMO have more significant catalytic activity than LSM after polarization, resulting in 32% higher current densities, lower electrical resistance after polarization, and a 21% increase in power density.

Network slicing is a primary Fifth-Generation (5G) mobile networking technology to create virtualised and softwarised logical networks for various vertical businesses with diverging Quality of Service (QoS) requirements. Meanwhile, there is a clear gap in providing network slicing capabilities in 5G multi-tenant networks to enable guaranteed QoS in terms of well-defined network metrics for the multiple tenants sharing the same physical infrastructure. This article designs and implements novel software data path architecture that enables such network slicing with assured QoS in 5G multi-tenant networks. Highly flexible and customisable definition of network slicing is also allowed to be aligned with different existing definitions on demand and at run time. The proposed architecture has been prototyped based on the popular Open Virtual Switch (OVS), and empirically validated to demonstrate the deployment and management of network slices with the above capabilities. Intensive scalability results are provided where more than 8,192 network slices are achieved simultaneously with warranted QoS through performance isolation in terms of bandwidth and delay in a real softwarised 5G multi-tenant infrastructure at speeds of up to 10 Gbps.

The current need for handheld electronic devices with high energy autonomy has amplified research into clean and mobile energy source developments. Among suitable and promising technologies for this application, fuel cells, FCs are highlighted because of their minimal emission of pollutants and high efficiency. One type of FCs that has yet to be studied is the hydrogen peroxide/direct hydrogen peroxide fuel cell (DPPFCs). The present work is dedicated to the development of DPPFCs of one compartment using copper hexacyanoferrates (CuHCFs) as cathodic material and a Ni grid as anodic material. CuHCFs containing FeII and/or FeIII were synthesized, characterized and their electrocatalyst performances were compared in 0.1 mol L−1 HCl and 0.5 mol L−1 H2O2. The maximum power densities reached for the CuFeII was 8.3 mW cm−2 and for the CuFeIIFeIII was 2.9 mW cm−2. The CuHCFs cathode materials show promising results, standing out as innovative materials for such an application.

Made available in DSpace on 2020-12-12T02:42:02Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-07-01 An easy and effective method for the preparation of a new impedimetric sensor used in the detection of dimethyl sulfide (DMS) at a nanomolar level is presented. The sensor was prepared in two steps from a commercially available screen-printed carbon electrode (SPCE): a simple activation of the SCPE using cyclic voltammetry followed by electroless plating of the working electrode surface with gold clusters. Scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDX) techniques confirmed the successful functionalization of the SPCE, revealing the presence of gold particles dispersed on the carbon matrix. Electrochemical impedance spectroscopy (EIS) was used to study the sensitivity of the sensor towards DMS dissolved in aqueous solution and simulated ocean water. Analyses were performed in less than 3 min, and the sensor showed linearity in a concentration range from 1.0 × 10−10 to 1.0 × 10−8 M with a limit of detection of 1.50 × 10−9 M and a limit of quantification of 2.27 × 10−9 M. To simulate the marine environment in which DMS is naturally present in nature, the impedance of the sensor was monitored by online EIS. Moreover, results indicated that, despite not linearly, the sensor is a promising tool to detect the analyte even at 1.0 × 10−11 M, presenting an increase of resistance of 13.5% in relation to its bare condition. Center for Optics Photonics and Lasers (COPL) Université Laval CDN Isotopes Department of Chemical Engineering Universidade Federal de Minas Gerais (UFMG) Laboratory of Applied Immunology Fundação Ezequiel Dias (FUNED) Department of Chemistry Universidade Federal de Minas Gerais (UFMG) Institute of Chemistry UNESP Institute of Chemistry UNESP

Made available in DSpace on 2020-12-11T17:02:17Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-06-01 Natural Sciences and Engineering Research Council of Canada (CRSNG) Canadian Funding for Infrastructure (CFI) Canada Excellence Research Chair in Photonics Innovations (CERCP) Screen-printed carbon electrode (SPCE) was examined as a transducer substrate for application in electrochemical sensors. Aqueous solutions of 0.1 M KCl and 0.1 M KCl + 5 mM K-3[Fe(CN)(6)]/K-4[Fe(CN)(6)] (redox solution) were prepared to simulate the environment of faradaic and non-faradaic sensing, respectively. The SPCE presented an irregular surface composed by two main carbon phases. Raman spectroscopy results revealed the presence of peaks around 1,580 cm(-1) and 1,334 cm(-1) related to the G and D bands corresponding to sp(2) carbon atoms (graphite flakes) and a multitude of broad bands associable to amorphous sp(3) carbon in the ink matrix. Conductive atomic force microscopy indicated that the irregular structure of the SPCE led to the heterogeneous distribution of the current over the surface and the electroactivity of this material was mainly attributed to the presence of graphite. Polarization curves and electrochemical impedance spectroscopy (EIS) revealed that the redox solution was more aggressive to the SPCE, despite this electrode was achieved a quasi-steady state for 1 h under the effect of a polarization potential in both electrolytes, which justifies its use as an electrochemical transducer in faradaic and non-faradaic devices. Univ Fed Minas Gerais UFMG, Dept Chem Engn, BR-30270901 Belo Horizonte, MG, Brazil Univ Laval, Ctr Opt Photon & Lasers COPL, Quebec City, PQ G1V 0A6, Canada Fundacao Ezequiel Dias FUNED, Dept Appl Immunol, BR-30510010 Belo Horizonte, MG, Brazil Univ Fed Minas Gerais UFMG, Dept Chem, BR-30270901 Belo Horizonte, MG, Brazil UNESP, Inst Chem, BR-14800060 Araraquara, SP, Brazil UNESP, Inst Chem, BR-14800060 Araraquara, SP, Brazil

This study aimed to design and fabricate novel hydroxypropyl-β-cyclodextrin-based hypercrosslinked polymers, called nanosponges, as carriers for anticancer hydrophobic agents and compare them with host–guest complexes of hydroxypropyl-β-cyclodextrin, a remarkable solubilizer, to investigate their application in improving the pharmaceutical properties of the flavonoid naringenin, a model hydrophobic nutraceutical with versatile anticancer effects. For this purpose, three new nanosponges, crosslinked with pyromellitic dianhydride, citric acid, and carbonyldiimidazole, were fabricated. The carbonate nanosponge synthesized by carbonyldiimidazole presented the highest naringenin loading capacity (≈19.42%) and exerted significantly higher antiproliferative effects against MCF-7 cancer cells compared to free naringenin. Additionally, this carbonate nanosponge formed a stable nanosuspension, providing several advantages over the naringenin/hydroxypropyl-β-cyclodextrin host–guest complex, including an increase of about 3.62-fold in the loading capacity percentage, sustained released pattern (versus the burst pattern of host–guest complex), and up to an 8.3-fold increase in antiproliferative effects against MCF-7 cancer cells. Both naringenin-loaded carriers were less toxic to L929 murine fibroblast normal cells than MCF-7 cancer cells. These findings suggest that hydroxypropyl-β-cyclodextrin-based carbonate nanosponges could be a good candidate as a drug delivery system with potential applications in cancer treatment.

The great variability of cancer types demands novel drugs with broad spectrum, this is the case of Nisin, a polycyclic antibacterial peptide that recently has been considered for prevention of cancer cells growth. As an accepted food additive, this drug would be very useful for intestinal cancers, but the peptide nature would make easier its degradation by digestion procedures. For that reason, the aim of present study to investigate the protective effect of two different β-cyclodextrin-based nanosponges (carbonyl diimidazole and pyromellitic dianhydride) and their anti-cancer enhancement effect of Nisin-Z encapsulated with against colon cancer cells (HT-29). To extend its possible use, a comparison with breast (MCF-7) cancer cell was carried out. The physicochemical properties, loading efficiency, and release kinetics of Nisin complex with nanosponges were studied. Then, tricin-SDS-PAGE electrophoresis was used to understand the effect of NSs on stability of Nisin-Z in the presence of gastric peptidase pepsin. In addition, the cytotoxicity and cell membrane damage of Nisin Z were evaluated by using the MTT and LDH assay, which was complemented via Annexin-V/ Propidium Iodide (PI) by using flowcytometry. CD-NS are able to complex Nisin-Z with an encapsulation efficiency around 90%. A protective effect of Nisin-Z complexed with CD-NSs was observed in presence of pepsin. An increase in the percentage of apoptotic cells was observed when the cancer cells were exposed to Nisin Z complexed with nanosponges. Interestingly, Nisin Z free and loaded on PMDA/CDI-NSs is more selectively toxic towards HT-29 cells than MCF-7 cancer cells. These results indicated that nanosponges might be good candidates to protect peptides and deliver drugs against intestinal cancers.

The ability of cyclodextrins to enhance the water solubility of lipophilic compounds is used to modify the water-based Oxygen Radical Absorbance Capacity (ORAC) method to measure antioxidant activity in vitro. However, the use of these solubility enhancers may alter fluorescent readings, which has led to contradictory results being described in the literature. The low specificity of these oligosaccharides and their controlled release effect can result in cyclodextrins forming inclusion complexes with other reagents in the assay, changing the kinetics. In this study, the cause of cyclodextrins' interference in the ORAC method is evaluated through a physicochemical and computational approach. Cyclodextrins showed a clear increase in the fluorescent signal both in the presence and absence of the antioxidant oxyresveratrol, the precise effect being dependent on the type and concentration of cyclodextrin. Although the glucidic nature of cyclodextrins could play a minimal role in this effect, it seems that the main cause was the encapsulation of other substrates in the reaction, fluorescein and AAPH.

In this work, two catalysts, lanthanum manganite strontium-doped perovskite without (LSM) and with (LSMMO) mixed molybdenum oxides, were synthesized by the sol-gel route and deposited by immersion in carbon cloth substrates. Their performance as cathodes in the hydrogen peroxide reduction reaction (HPRR) and oxygen reduction reaction (ORR) was investigated through cyclic voltammetry and electrochemical impedance spectroscopy, the electrocatalytic efficiency of these electrodes in the HPRR was analyzed in KOH and H2O2 medium at 298 K. The performance of the cathodes, in a single compartment, using a nickel plate as an anode was also investigated. The results showed that for the reduction reactions, electrodes developed with LSMMO have more significant catalytic activity than LSM after polarization, resulting in 32% higher current densities, lower electrical resistance after polarization, and a 21% increase in power density.

In this article, we used monolayer two dimensional (2D) and 3D multicellular spheroid models to improve our understanding of the gene delivery process of a new modified cationic hyper-branched cyclodextrin-based polymer (Ppoly)-loaded plasmid encoding Enhanced Green Fluorescent Protein (EGFP). A comparison between the cytotoxicity effect and transfection efficiency of the plasmid DNA (pDNA)-loaded Ppoly system in 2D and 3D spheroid cells determined that the transfection efficiency and cytotoxicity of Ppoly–pDNA nanocomplexes were lower in 3D spheroids than in 2D monolayer cells. Furthermore, histopathology visualization of Ppoly–pDNA complex cellular uptake in 3D spheroids demonstrated that Ppoly penetrated into the inner layers. This study indicated that the Ppoly, as a non-viral gene delivery system in complex with pDNA, is hemocompatible, non-toxic, high in encapsulation efficiency, and has good transfection efficiency in both 2D and 3D cell cultures compared to free pDNA and lipofectamine (as the control).

This document reports the up-to-date progress towards achieving smart E2E network slicing. It focuses on the prototyping of enabling technologies for E2E network slicing across network segments, their intent-based Management and Orchestration, and AI-based RAN resource allocation enabled with the Cognitive Plane’s Multi-Agent Deep Reinforcement Learning platform. Moreover, it covers preliminary integration work between different network slicing enablers over the E2E data path, with the MANO plane, and with the MA-DRL platform. Together, these technological enablers, algorithmic advances and initial integration work lay down the foundation for implementing the targeting E2E slicing system.

Macrolides are widely used antibiotics with a broad spectrum of activity. The development of drug carriers to deliver this type of antibiotics has attracted much research. The present study aims at developing new swellable dextrin-based nanohydrogels for the topical delivery of rokitamycin, as model macrolide. Rokitamycin is a synthetic analogous of macrolides with advantageous characteristics as far as bacterial uptake and post-antibiotic effect are concerned. It is also indicated for the treatment of severe infections caused by Acanthamoeba and for topical infections. The nanohydrogels have been prepared from two types of cross-linked polymers obtained by using β-cyclodextrin or Linecaps® was provided by the Roquette Italia SPA (Cassano Spinola, Al, Italy) as building blocks. The cross-linked polymers have been then formulated into aqueous nanosuspensions refined and tuned to achieve the incorporation of the drug. Cross-linked β-cyclodextrin (β-CD) and Linecaps® (LC) polymers formed dextrin-based nanohydrogels with high swelling degree and mucoadhesion capability. Rokitamycin was loaded into the nanohydrogels displaying an average size around 200 nm with negative surface charge. In vitro kinetic profiles of free and loaded drug in nanohydrogels were compared at two pH levels. Interestingly, a sustained and controlled release was obtained at skin pH level due to the high degree of swelling and a pH responsiveness possibly. The results collected suggest that these nanohydrogels are promising for the delivery of rokitamycin and may pave the way for the topical delivery of other macrolide antibiotics.

Background 2-Phenylethanol (PEA) is a higher aromatic alcohol with a rose-like odor, which is used in several industries. Although PEA can be synthesized, consumers are increasingly concerned about the toxicity of chemically synthesized products, and prefer natural aroma compound. PEA occurs naturally in the environment but concentrations are too low to justify extraction. Results The present study offers a novel biological source of PEA: the filamentous fungi Monochaetinula geoffroeana. We report the highest recorded yield of PEA of fungal origin to date: 6.52 g L-1 . The volatility and low water solubility of PEA can affect its use in many industries, for which reason complexation studies of PEA and cyclodextrins were carried out using the phase solubility technique. PEA formed 1:1 stoichiometric inclusion complexes with natural and modified CDs, the highest encapsulation constant being obtained with MβCD (K1:1 = 299.88 L mol-1 ). The complexation process significantly increased the water solubility of PEA. A computational study showed a high degree of correlation between computed scores and experimental values. Furthermore, this study reports the role of salicylic acid as an effective elicitor for improved PEA production by the studied fungi. Supplementation with 10 μmol L-1 salicylic acid increased PEA production from 6.52 to 10.54 g L-1 . Conclusion The best treatment to enhance PEA production by M. geoffroeana under laboratory conditions was to use salicylic acid 10 μmol L-1 . Due to the commercial importance of PEA, further investigation is needed to improve PEA production by M. geoffroeana and to optimize culture conditions in order to standardize yields. © 2021 Society of Chemical Industry.

Cyclodextrin-based nanosponges (CD-NSs) have gained importance in drug delivery in the last years due to their easy synthesis and versatility. However, their use as carriers for the delivery of macromolecules such as proteins is less known and sometimes difficult to consider. In this entry, the authors summarize and highlight the multiple possibilities of CD-NSs to deliver active proteins, improving their activity or stability. Starting with a brief description of CD-NSs and their characteristics, the entry will be focused on several proteins, such as (1) Lipase, (2) Insulin and (3) Nisin, for chemical or pharmaceutical applications. The revised results demonstrated that CD-NSs can generate different and interesting applications with proteins. These results could be added to their uses with small drugs, being an interesting alternative for protein delivery and applicability.

This document reports the up-to-date progress towards achieving smart E2E network slicing. It focuses on the preliminary design and prototyping of enabling technologies for E2E network slicing across network segments. Moreover, it provides initial investigations into the algorithm design of AI-based radio link control and RAN slice scheduler, as well as integration aspects of Management-Orchestration and Cognitive Plane development kit. Together, these enablers form basic building blocks for deeper integrations, technologically and algorithmically, between partners in future implementation of the targeting E2E slicing system.

Cyclodextrins (CDs) are a good alternative to reduce or enhance different biomolecule characteristics and have demonstrated great results in food science. However, CDs present intrinsic limitations that can be solved by derivative synthesis. This review represents a survey of the state of the art of CD-based materials and their uses in food science. A deep review of the structure is carried out and different groups for ordination are suggested. After that, different applications such as cholesterol complexation or its use as sensors are reviewed. The derivatives show novel and promising activities for the industry. A critical perspective of the materials suggests that they might not present toxicity, although more studies are required. These points suggest that the research in this field will be increased in the following years.

Background: Plasma concentration of natalizumab falls above the therapeutic threshold in many patients who, therefore, receive more natalizumab than necessary and have higher risk of progressive multifocal leukoencephalopathy.Objective: To assess in a single study the individual and treatment characteristics that influence the pharmacokinetics and pharmacodynamics of natalizumab in multiple sclerosis (MS) patients in the real-world practice.Methods: Prospective observational study to analyse the impact of body weight, height, body surface area, body mass index, gender, age, treatment duration, and dosage scheme on natalizumab concentrations and the occupancy of α4-integrin receptor (RO) by natalizumab.Results: Natalizumab concentrations ranged from 0.72 to 67 μg/ml, and RO from 26 to 100%. Body mass index inversely associated with natalizumab concentration (beta = −1.78; p ≤ 0.001), as it did body weight (beta = −0.34; p = 0.001), but not height, body surface area, age or gender Extended vs. standard dose scheme, but not treatment duration, was inversely associated with natalizumab concentration (beta = −7.92; p = 0.016). Similar to natalizumab concentration, body mass index (beta = −1.39; p = 0.001) and weight (beta = −0.31; p = 0.001) inversely impacted RO. Finally, there was a strong direct linear correlation between serum concentrations and RO until 9 μg/ml (rho = 0.71; p = 0.003). Nevertheless, most patients had higher concentrations of natalizumab resulting in the saturation of the integrin.Conclusions: Body mass index and dosing interval are the main variables found to influence the pharmacology of natalizumab. Plasma concentration of natalizumab and/or RO are wide variable among patients and should be routinely measured to personalize treatment and, therefore, avoid either over and underdosing.

This study tested the anticoagulant effect of cyclodextrin (CD) hyper-branched-based polymers (HBCD-Pols). These polymers were synthesized and tested for their coagulant characteristics in vitro and in vivo. Due to their polymeric structure and anionic nature, the polymers can chelate Ca2+, reducing the free quantity in blood. HBCD-Pol increased the blood clotting time, PT, and aPTT 3.5 times over the control, showing a better effect than even ethylenediaminetetraacetic acid (EDTA), as occured with recalcification time as well. A titration of HBCD-Pol and EDTA showed exciting differences in the ability to complex Ca2+ between both materials. Before executing in vivo studies, a hemocompatibility study was carried out with less than 5% red blood cell hemolysis. The fibrinogen consumption and bleeding time were analyzed in vivo. The fibrinogen was considerably decreased in the presence of HBCD-Pol in a higher grade than EDTA, while the bleeding time was longer with HBCD-Pols. The results demonstrate that the anticoagulant effect of this HBCD-Pol opens novel therapy possibilities due to the possible transport of drugs in this carrier. This would give combinatorial effects and a potential novel anticoagulant therapy with HBCD-Pol per se.

Magnetically driven nanosponges with potential application as targeted drug delivery systems were prepared via the addition of magnetite nanoparticles to the synthesis of cyclodextrin and maltodextrin polymers crosslinked with 1,1′-carbonyldiimidazole. The magnetic nanoparticles were obtained separately via a coprecipitation mechanism involving inorganic iron salts in an alkaline environment. Four composite nanosponges were prepared by varying the content of magnetic nanoparticles (5 wt% and 10 wt%) in the cyclodextrin- and maltodextrin-based polymer matrix. The magnetic nanosponges were then characterised by FTIR, TGA, XRD, FESEM, and HRTEM analysis. The magnetic properties of the nanosponges were investigated via magnetisation curves collected at RT. Finally, the magnetic nanosponges were loaded with doxorubicin and tested as a drug delivery system. The nanosponges exhibited a loading capacity of approximately 3 wt%. Doxorubicin was released by the loaded nanosponges with sustained kinetics over a prolonged period of time.

Introduction In the last few years, a new T cell therapy, chimeric antigen receptor-T (CAR-T) cells, has been developed. CAR-T cells are highly effective at inhibiting antitumor activity, but they can cause a wide spectrum of unusual side effects. Areas covered The present review provides an overview of the adverse events of CAR-T cell therapy, focusing on cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, increased risk of infections, and other long-term complications. Representative studies addressing the safety and efficacy of CAR-T cell therapy are summarized. Expert opinion In the coming years, we predict a great expansion in the use of CAR-T cell therapy with it applied to a higher number of patients with both malignant neoplasms and immune-mediated diseases. Despite physicians and patient expectations about the potential of this therapy, there are still several barriers that may limit providers' ability to supply quality care. This exciting and powerful new therapy requires the formation of new multidisciplinary teams to carry out a safe treatment administration and to successfully manage the resultant complications. The follow-up of these therapies is important for two aspects: effectiveness in different populations and real-life safety in short and in long-term follow-up.

Different physical parameters of boxes containing batches of RFID-tagged items can be estimated by making smart use of standard information available during interrogation, such as the number of tags identified, the number of collisions, the average power measured in the slots, and so forth. This process can be used for many purposes, such as adding a measuring capacity to a gate without extra-hardware, checking whether the boxes fit their manifest, detecting unusually distributed boxes that require different processing, etc. In this paper, these features are used as input information in a supervised learning model based on Artificial Neural Networks (ANNs), which outputs the box size estimation among a set of possible box size candidates. This model has been trained using standard sizes of boxes, which are fed into a UHF RFID gate simulator that introduces random perturbations in the orientation, the position, and the number of tags in the boxes. The accuracy of the model is about 90% for an 8 candidate boxes setup. Thus, the model can be considered suitable to be further investigated.

Inflammation is a biological response of the immune system to harmful stimuli. Importantly, inflammation is also a hallmark of several human diseases such as cancer or diabetes. Novel drugs to treat this response are constantly researched, but the formulation is usually forgotten. Cyclodextrins (CDs) are a well-known excipient for complexing and drug delivery. Anti-inflammatory drugs and bioactive compounds with similar activities have been favored from these CD processes. CDs also illustrate anti-inflammatory activity per se. This review tried to describe the capacities of CDs in this field, and is divided into two parts: Firstly, a short description of the inflammation disease (causes, symptoms, treatment) is explained; secondly, the effects of different CDs alone or forming inclusion complexes with drugs or bioactive compounds are discussed.

This document reports all the activities and outcomes related to the definition of the network requirements, key function blocks and system architecture for the 6G BRAINS project. Based on a methodology informed by use case requirements etc., the deliverable presents an overall logical architecture with key function blocks defined and organised into operational planes. Based on the logical architecture, detailed functional architectures are defined to address the major technical challenges in the project.

This is an abstrat submitted and accepted in the CinC conference 2021

The discovery of antifibrotic agents have resulted in advances in the therapeutic management of idiopathic pulmonary fibrosis (IPF). Currently, nintedanib and pirfenidone have become the basis of IPF therapy based on the results of large randomized clinical trials showing their safety and efficacy in reducing disease advancement. However, the goal of completely halting disease progress has not been reached yet. Administering nintedanib with add-on pirfenidone is supposed to enhance the therapeutic benefit by simultaneously acting on two different pathogenic pathways. All this becomes more important in the context of the ongoing global pandemic of coronavirus disease 2019 (COVID-19) because of the fibrotic consequences following SARS-CoV-2 infection in some patients. However, little information is available about their drug–drug interaction, which is important mainly in polymedicated patients. The aim of this review is to describe the current management of progressive fibrosing interstitial lung diseases (PF-ILDs) in general and of IPF in particular, focusing on the pharmacokinetic drug-drug interactions between these two drugs and their relationship with other medications in patients with IPF.

Resumen La ruta de senalizacion de las proteinas de la familia Janus cinasa (JAK) esta implicada en la patogenia de muchas enfermedades inflamatorias y autoinmunitarias, como la artritis reumatoide (AR), la psoriasis y la enfermedad inflamatoria intestinal. Una gran cantidad de citocinas implicadas en el desarrollo de estas enfermedades utilizan esta via de senalizacion para transducir senales intracelulares. En los ultimos anos, la aparicion de los inhibidores de las proteinas JAK (jakinibs) ha demostrado que los farmacos relacionados con esta ruta patogenica pueden tener gran aplicabilidad clinica. Tofacitinib y baricitinib, primeros jakinibs aprobados para el tratamiento de la AR, estan en estudio para el tratamiento de otras enfermedades autoinmunitarias. Asimismo, otros jakinibs se encuentran en diferentes fases de desarrollo. En este trabajo se revisan los principales aspectos en cuanto a eficacia, interacciones farmacologicas y seguridad tanto de los jakinibs clasicos como de los de nueva generacion.

Queued Radio Frequency Identification (RFID) networks arise naturally in many applications, where tags are grouped into batches, and each batch must be processed before the next reading job starts. In these cases, the system must be able to handle all incoming jobs, keeping the queue backlogs bounded. This property is called stability. Besides, in RFID networks, it is common that some readers cannot operate at the same time, due to mutual interferences. This fact reduces the maximum traffic that readers can process since they have to share the channel. Synchronous networks share the channel using a TDMA approach. The goal of this work is to analytically determine whether a synchronous queued RFID network attains stable operation under a given incoming traffic. Stability depends on the service rate, which is characterized in this paper using an exact numerical method based on a recursive analytical approach, overcoming the limitations of previous works, which were based on simplifications. We also address different flow optimization problems, such as computing the maximum joint traffic that a network can process stably, selecting the minimal number of readers to process a given total load, or determining the optimal timeslot duration, which are novel in the RFID literature. Ministerio de Economía, Industria y Competitividad | Ref. TEC2016-76465-C2-1-R

As the most common cancer in women, efforts have been made to develop novel nanomedicine-based therapeutics for breast cancer. In the present study, the in silico curcumin (Cur) properties were investigated, and we found some important drawbacks of Cur. To enhance cancer therapeutics of Cur, three different nonionic surfactants (span 20, 60, and 80) were used to prepare various Cur-loaded niosomes (Nio-Cur). Then, fabricated Nio-Cur were decorated with folic acid (FA) and polyethylene glycol (PEG) for breast cancer suppression. For PEG-FA@Nio-Cur, the gene expression levels of Bax and p53 were higher compared to free drug and Nio-Cur. With PEG-FA-decorated Nio-Cur, levels of Bcl2 were lower than the free drug and Nio-Cur. When MCF7 and 4T1 cell uptake tests of PEG-FA@Nio-Cur and Nio-Cur were investigated, the results showed that the PEG-FA-modified niosomes exhibited the most preponderant endocytosis. In vitro experiments demonstrate that PEG-FA@Nio-Cur is a promising strategy for the delivery of Cur in breast cancer therapy. Breast cancer cells absorbed the prepared nanoformulations and exhibited sustained drug release characteristics.

This paper sketches an interpretive framework for examining the general outlines of current literacy theories and their approaches in teachers training programs. It contains four sections. The first section reviews the bases of new studies of literacy. The second section presents a discussion about some tensions between conceptions of literacy and essential concepts to understand the functioning of language in social practices. A discussion about literacy practices in teachers training programs is presented in the third section. Finally, I consider essential for mother-tongue classes to be centered on the dynamics of social interactions, at the various levels of teaching, as a way to trigger the learning processes aimed at. Under this perspective, the text discusses the relevance of approaching discourse genres in order to assure the development of essential abilities for the subject to act in the various language practices he/ she may come across. Key words: literacy, genres studies, teachers training. Este artigo discute e reflete sobre princípios gerais de trabalhos recentes acerca do letramento e suas abordagens em cursos de formação de professores. O texto divide-se em quatro seções. Na primeira, retomo as bases dos chamados “novos estudos do letramento”. A segunda seção discute algumas tensões entre concepções de letramento e conceitos a elas relacionados. A terceira seção é dedicada à discussão das práticas de letramento na formação de professores. Na última seção, defendo a importância de as aulas de língua materna, em seus diferentes níveis, serem centradas na dinâmica das interações sociais, como forma de desencadear os processos de aprendizagem visados. Nessa perspectiva, o texto discute a relevância dos gêneros do discurso para o desenvolvimento, pelo sujeito, de habilidades essenciais para agir em diferentes práticas de linguagem das quais participa. Palavras-chave: letramento, gêneros do discurso, formação de professores.

This chapter presents the most relevant advances achieved during the MIDES project in relation to material development of key elements for microbial desalination cells. The first section is devoted to electrodes. Providing a general overview of the requirements of carbon-based materials to serve either as anodes or cathodes for microbial desalination cells. Advances achieved during MIDES in the development of materials for anode and cathode application are listed. The second section is focussed on ion-exchange membranes for microbial desalination cells. General considerations for the use of these membranes are reported as well as key parameters. Finally, advances in ion-exchange membrane development, in terms of antifouling and their performance in desalination trials, achieved during the MIDES project, are reported.

This chapter presents the most relevant advances achieved during the MIDES project in relation to material development of key elements for microbial desalination cells. The first section is devoted to electrodes. Providing a general overview of the requirements of carbon-based materials to serve either as anodes or cathodes for microbial desalination cells. Advances achieved during MIDES in the development of materials for anode and cathode application are listed. The second section is focussed on ion-exchange membranes for microbial desalination cells. General considerations for the use of these membranes are reported as well as key parameters. Finally, advances in ion-exchange membrane development, in terms of antifouling and their performance in desalination trials, achieved during the MIDES project, are reported.

Cyclodextrins (CDs) and cyclodextrin (CD)-based polymers are well-known complexing agents. One of their distinctive features is to increase the quantity of a drug in a solution or improve its delivery. However, in certain instances, the activity of the solutions is increased not only due to the increase of the drug dose but also due to the drug complexation. Based on numerous studies reviewed, the drug appeared more active in a complex form. This review aims to summarize the performance of CDs and CD-based polymers as activity enhancers. Accordingly, the review is divided into two parts, i.e., the effect of CDs as active drugs and as enhancers in antimicrobials, antivirals, cardiovascular diseases, cancer, neuroprotective agents, and antioxidants.