Monoclonal Antibodies for Asthma Management

Asthma is a multifactorial and complex disease, with different degrees of risks and severity, as well as the response to treatment. Medications currently available are most effective in severe asthma; nonetheless, there is a percentage of patients that have no response to the treatment that guidelines suggest in their recommendations. In the last years, there have been new insights in inflammatory molecules that contribute to asthma physiopathology and a lot of them have been considered to be possible targets in the management of severe asthma. As a consequence of this, a few monoclonal antibodies have been developed evidencing their effectiveness in the treatment of the disease. The study of these new therapies has allowed the identification of specific inflammatory pathways. This chapter intends to offer a critical perspective of the current guidelines for the management of severe asthma, as well as to discuss current treatments and the future on new molecules. Through an adequate characterization, different phenotypes will be recognized and associated with a determinate biomarker and should be used to select the treatment that can offer the highest efficiency in these patients. In this way, the treatment will be directed to a personalized medicine

Implications of iron nanoparticles in spontaneous coal combustion and the effects on climatic variables

Atmosphere, water, and soil contamination with toxic compounds is a recurrent issue due to environmental disasters, coal burning, urbanization, and industrialization, allf of which have contributed to soil contamination over the decades. Consequently, understanding of the nanomineralogy and potential hazardous elements (PHEs) in coal area soil are always a vital topic since contaminated soil can affect the environment, agricultural safety, and human health. Colombian coal mining in the La Guajira zone has been usually been related with important health and ecological effects. Coalmine rejects from active and/or abandoned operations are causes of high intensities of potential hazardous elements (PHEs) and nanoparticles (NPs, minerals and/or amorphous compounds). Although these pollutants can be reduced by sorption to NPs, in this study was recognized an analytical procedure for understand distribution of PHEs and their relationship to iron NPs(Fe-NPs) was recognized. Non and poorrly crystalline Fe-NPs performances as the major PHEs association. This complex interaction is constant and efficient in resolving PHEs in proportions above monitoring quantities. The indefinite basis of PHEs in Colombian (La Guajira area) coalmine rejects sources results in years-long leaching of PHEs into rivers and drainages. The iron-clays and their great geomobility interfere the mitigating character that Fe hydr/oxides alone show through adsorption of PHEs and their control in spontaneous coal combustion (SCC) zones. This can have significant consequences to the probable availability of several pollutants (e.g. drinking water). The new results presented in this study add novel viewpoints into the description of Fe-NPs and its incidence in SCC areas. The methodology utilized in this work can be applied as a supplementary technique to evaluate the influence of coalmining actions on ecological and human health

Testing of a resistive sensor with fabric medium for monitoring frost formation in refrigeration systems

Refrigeration is one of the key elements for food preservation. With global temperatures increasing due to global warming, the efficiency in refrigerated storage systems must be improved. One of the problems that is yet to be solved in these systems is the efficient and accurate removal of the frost formed on the heat exchanger surface. In previous works, a low-cost resistive sensor has been developed to detect frost formation for accurate removal. This paper shows the results of an experimental study carried out to increase the accuracy, by placing different configurations of a fabric medium in between the sensor electrodes.This study is within the activities of project “Pack2Life – High performance packaging”, project IDT in consortium No.33792, call No.03/SI/2017, Ref. POCI-01-0247-FEDER-033792, promoted by COMPETE 2020 and co-funded by FEDER within Portugal 2020. This work has been supported by the project Centro-01-0145-FEDER000017 - EMaDeS - Energy, Materials and Sustainable Development, co-funded by the Portugal 2020 Program (PT 2020), within the Regional Operational Program of the Center (CENTRO 2020) and the European Union through the European Regional Development Fund (ERDF). The authors thank the opportunity and financial support to carry on this project to Fundação para a Ciência e Tecnologia (FCT) and R&D Unit "Centre for Mechanical and Aerospace Science and Technologies" (C-MAST), under project UIDB/00151/2020.info:eu-repo/semantics/publishedVersio

Experimental Study of Thermal Performance of Different Fruit Packaging Box Designs

Packaging was recently identified as an essential element in addressing the key challenge of sustainable food supply and is gaining interest among researchers. It is a central element in food quality preservation due to its role in heat and mass exchange with the external atmosphere, contributing to the preservation of food quality during storage and extending food shelf life. This work proposes three new packaging configurations with the same size but different geometry and ventilation hole sizes and geometry, that change the conditions in which the heat and mass exchange occurs, during either the cooling period of fruits, inside the cooling chamber, or during the period when the packaging is exposed to ambient conditions, outside the cooling chamber. For this purpose, packages with fruit models that replicate the properties of real fruit were subjected to a cooling process inside a cooling chamber for 8 h. Subsequently, during the heating phase, the packages were exposed to ambient conditions for 10 h. Thermal conditions were also monitored, both inside and outside the chamber. Additionally, for comparative purposes, the thermal behavior of commercial packaging was also evaluated for the same operating conditions in the cooling and heating phases. The results show that the new packages do not substantially promote the preservation of fruits in the cooling phase, but in the heating phase, they ensure an extension of the period with proper thermal conditions of up to 50% in relation to the conventional packaging. This result is particularly important since the heating phase, in which fruits are outside the storage chamber, is the period with the greatest impact on the fruits’ useful life.This study was conducted within the activities of project “Pack2Life—High performance packaging”, project IDT in consortium n. 33792, call n. 03/SI/2017, Ref. POCI-01-0247-FEDER- 033792, promoted by COMPETE 2020 and co-funded by FEDER within Portugal 2020. The authors are grateful for the opportunity and financial support to continue this project to Fundação para a Ciência e a Tecnologia (FCT) and R&D Unit “Centre for Mechanical and Aerospace Science and Technologies” (C-MAST), under project UIDB/00151/2020.info:eu-repo/semantics/publishedVersio

Multiple hazardous elements in nanoparticulate matter from a Caribbean industrialized atmosphere

Modern microscopy studies are capable of revealing ultra-fine particles (UFPs) and nanoparticles (NPs) that are produced in the processes related to traffic vehicular, industrial, metropolitan, and marine aerosol dry deposition in the coastal zones. Especially, secondary aerosol passages complexes categories of NPs and UFPs, which can be accumulated on construction compounds and by dry deposition, encourages multiples monuments deterioration routes. The advanced electron microscopies method is one of the most utilized in environmental studies. Between the different industrial areas in the world, the Caribbean area is the most relevant symbols of air quality due to climatic conditions with strong winds, but this study shows that regionally the most industrialized region does not have an adequate air quality. In the present work, electron microscopy analyses are used to describe of the extent of ultra-fine particle and nanoparticles in walls in contact to weathering. Numerous phases were recognized by advanced mineralogy methods. Thanks to the new analytical procedure it was feasible to understand NPs and UFPs; the occurrence of potential hazardous elements (PHEs), most of them as minerals but also combined in multiple accumulations with Al–Cr–Fe–K–Mg–Pb–Si–Ti–Zn amorphous; and carbonaceous phases

Dynamics and Development of Extensively Drug-resistant Tuberculosis, Portugal

Abstrat publicado em: http://www.pasteur.fr/infosci/conf/sb/tuberculosis2012/images/TB2012-Program-Abstract-book-LD.pdfThe development of multidrug-resistant (MDR) and extensive drug-resistant (XDR) tuberculosis(TB) combined with subsequent transmission constitutes a serious threat to the effective control of tuberculosis in several countries. Lisbon Health Region, despite great progresses in TB management still presents a high number of MDR/XDR-TB cases. The development of this type of resistance is the result of adaptative selection of Mycobacterium tuberculosis strains that acquire and accumulate specific mutations at specific genes. The presently known mechanisms of drug resistance include the modification or overexpression of drug targets, inactivation of drug- activator enzymes and overexpression of drug-modifying enzymes. Although the molecular basis of resistance of MDR/XDR-TB strains circulating in Lisbon has already been addressed in different studies, the dynamics or mode of resistance acquisition that have lead to the different circulating strains is still partially unclear. In the present study we have genotyped and screened a set of 44 MDR/XDR-TB isolates for mutations in tlyA, gyrA, rrs and eis genes. We have determined the most prevalent mutations found in each gene to be Ins755GT in tlyA, A1401G in rrs, G-10A in eis and S91P in gyrA. Two genetic clusters previously known to be associated with XDR-TB were detected, Lisboa3 and Q1, containing 27 and 17 isolates, respectively. Lisboa3 strains isolated in the 90’s with the same mutational profile of recent XDR-TB Lisboa3 strains were found, emphasizing the ancient XDR-TB problem in the region. Also investigated was the resistance level conferred by eis G-10A mutations, revealing that eis G-10A mutations may result in an undetectable AMK resistance. We concluded by analyzing the mutational distribution found by genetic cluster that in Q1 cluster two mutations, gyrA D94A and rrs A1401G, were enough to ensure development of XDR-TB from a multidrug resistant strain. Moreover, in Lisboa3 cluster it was possible to determine that the development of kanamycin low-level resistance mediated by eis promoter mutations was at the origin of independent emergence of several XDRTB strains that can be discriminated within Lisboa3 genetic cluster by tlyA mutations

Photodegradation of sulfamethoxazole in environmental samples: the role of pH, organic matter and salinity

Sulfamethoxazole (SMX) is the most representative antibiotic of the sulfonamides group used in both human and veterinary medicine, and thus frequently detected in water resources. This has caused special concern due to the pronounced toxicity and potential to foster bacterial resistance of this drug. Therefore, and to further understand the fate of SMX in the aquatic environment, its photodegradation under simulated solar radiation was here studied in ultrapure water and in different environmental samples, namely estuarine water, freshwater and wastewater. SMX underwent very fast photodegradation in ultrapure water, presenting a half-life time (t1/2) of 0.86 h. However, in environmental samples, the SMX photodegradation rate was much slower, with 5.4 h < t1/2 < 7.8 h. The main novelty of this work was to prove that pH, salinity and dissolved organic matter are determinant factors in the decrease of the SMX photodegradation rate observed in environmental samples and, thus, they will influence the SMX fate and persistence, potentially increasing the risks associated to the presence of this pollutant in the environment.publishe

Discovery of thiazolo [5,4-c] isoquinoline based compounds as acetylcholinesterase inhibitors through computational target prediction, molecular docking and bioassay

We thank Nathalie Reichmann and Leendert Hamoen (University of Amsterdam) for critical reading of the manuscript, Ana Velic (Proteome Center Tübingen) for help with proteome analysis and Mike VanNieuwenhze (Indiana University) for the generous gift of HADA. This study was funded by the European Research Council through grant ERC‐2017‐CoG‐771709 (to MGP), by national funds through FCT– Fundação para a Ciência e a Tecnologia, PTDC/BIA‐MIC/6982/2020 (to HV); PTDC/BIA‐PLA/3432/2012 (to SRF); FCT through MOSTMICRO‐ITQB R&D Unit (UIDB/04612/2020, UIDP/04612/2020) and LS4FUTURE Associated Laboratory (LA/P/0087/2020) and FCT fellowship SFRH/BD/147052/2019 (to BMS); by the Swiss National National Foundation through P300P3_155346 (to AJ); by the European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska‐Curie grant agreement No 839596 (to SS) and by the European Molecular Biology Organization through award ALTF 673‐2018 (to SS). Figure 6D and Appendix Fig S7 were created with Biorender.com .A computer-aided drug design (CADD) approach was developed for a focused chemical library comprising a series of sixteen thiazolo[5,4-c]isoquinoline derivatives. Little is known about this group of heteroaromatic compounds, both from the point of view of their synthesis and their biological properties. First, our CADD approach included target prediction by Mondrian conformal prediction with the ChEMBL database. The acetylcholinesterase (AChE) was identified as having a high probability of thiazolo[5,4-c]isoquinolines being active against it. Secondly, the molecular docking predictions revealed four promising thiazoloisoquinolines (2, 7, 13 and 14) according to their prominent ligand-protein energy scores and relevant binding affinities with the AChE pocket residues. The subsequent in vitro evaluation of promising hits and related ones revealed a set of novel AChE inhibitors. Therefore, the findings reported herein may provide a new strategy for discovering novel AChE inhibitors.publishersversionpublishe

Overview of phlorotannins’ constituents in Fucales

Fucales are an order within the Phaeophyceae that include most of the common littoral seaweeds in temperate and subtropical coastal regions. Many species of this order have long been a part of human culture with applications as food, feedand remedies in folk medicine. Apart from their high nutritional value, these seaweeds are also a well-known reservoir of multiple bioactive compounds with great industrial interest. Among them, phlorotannins, a unique and diverse class of brown algae-exclusive phenolics, have gathered much attention during the last few years due to their numerous potential health benefits. However, due to their complex structural features, combined with the scarcity of standards, it poses a great challenge to the identification and characterization of these compounds, at least with the technology currently available. Nevertheless, much effort has been taken towards the elucidation of the structural features of phlorotannins, which have resulted in relevant insights into the chemistry of these compounds. In this context, this review addresses the major contributions and technological advances in the field of phlorotannins extraction and characterization, with a particular focus on Fucales.This work received financial support from PT national funds (FCT/MCTES, Fundação para a Ciência e Tecnologia and Ministério da Ciência, Tecnologia e Ensino Superior) through the projects UIDB/50006/2020 and UIDP/50006/2020. Thanks to PTDC/BAA-AGR/31015/2017, “Algaphlor—Brown algae phlorotannins: From bioavailability to the development of new functional foods”, co-financed by the Operational Programme for Competitiveness and Internationalization— POCI, within the European Regional Development Fund (FEDER), and the Science and Technology Foundation (FCT), through national funds. Silva S. thanks FCT for funding through program DL 57/2016–Norma transitória (Ref. SFRH/BPD/74299/2010)