Adjuvants : an essential component of neisseria vaccines

Adjuvants may be classified into delivery systems and immune potentiator or modulator molecules based on their mechanism of action. Neisseria vaccines containing traditional adjuvants such as aluminium salts have existed for long time, but meningitis caused by Neisseria meningitidis serogroups, particularly serogroup B, continues to be a global health problem. Novel strategies have applied in silico and recombinant technologies to develop "universal" antigens (e.g. proteins, peptides and plasmid DNA) for vaccines, but these antigens have been shown to be poorly immunogenic even when alum adjuvanted, implying a need for better vaccine design. In this work we review the use of natural, detoxified, or synthetic molecules in combination with antigens to activate the innate immune system and to modulate the adaptive immune responses. In the main, antigenic and imune potentiator signals are delivered using nano-, micro-particles, alum, or emulsions. The importance of interaction between adjuvants and antigens to activate and target dendritic cells, the bridge between the innate and adaptive immune systems, will be discussed. In addition, nasal vaccine strategies based on the development of mucosal adjuvants and Neisseria derivatives to eliminate the pathogen at the site of infection provide promising adjuvants effective not only against respiratory pathogens, but also against pathogens responsible for enteric and sexually transmitted diseases

Recent Approaches for the Manufacturing of Polymeric Cranial Prostheses by Incremental Sheet Forming

This paper presents recent research experiences developed with the aim of manufacturing cranial prostheses in polymeric sheet using Incremental Sheet Forming (ISF) technologies. With this purpose, different approaches have been carried out in Single-Point Incremental Forming (SPIF) and Two-Point Incremental Forming (TPIF) in order to produce customized cranial implants using different polymeric materials. In this context, this research work provides a methodology to design and manufacture polymer customized cranial prostheses using the ISF technologies starting from a patient’s computerized tomography (CT). The results demonstrate the potential of manufacturing polymeric cranial prostheses by ISF in terms of the high formability achievable and show the appropriate geometrical accuracy at affordable manufacturing costs provided by these processes.Ministerio de Economía y Competitividad DPI2015-64047-

Parametric and machine learning-based analysis of the seismic vulnerability of adobe historical buildings damaged after the September 2017 Mexico earthquakes

In September 2017, two strong earthquakes hit the central region of Mexico, producing substantial damage to the historical buildings. A retroactive analysis for assessing the pre-event seismic vulnerability of these constructions allowed for testing the suitability of an existing parameter-based approach based on material and geometrical features. More than 160 adobe buildings in four municipalities of the State of Morelos were surveyed and included in a vulnerability-oriented GIS database. Data were collected on-site and managed by resorting to open-source GIS software combined with a Python-based database management tool and a cloud-based platform for onsite data collection using mobile devices. The parameter-based approach was used for assessing the analytical seismic vulnerability of the buildings and implementing a secondary, more conservative assessment that considers uncertainties associated with the data acquisition process. The capabilities of the database were further used to train a Machine Learning algorithm aimed at overcoming some representativeness limitations of the parameter-based analytical method. This third approach was found to be suitable for assessing the vulnerability of the building typologies addressed in this investigation. Although the implementation discussed in this paper is limited to a specific vernacular typology, it can be used to conduct customized local calibrations.- This work was partly financed by FCT/MCTES through national funds (PIDDAC) under the R & D Unit Institute for Sustainability and Innovation in Structural Engineering (ISISE), under reference UIDB/04029/2020. This research was funded by the Portuguese Foundation for Science and Technology (FCT) through grant number PD/BD/150385/2019. The field campaigns in the State of Morelos were financed by the Instituto de Ingenieria - Universidad Nacional Autonoma de Mexico (Institute of Engineering - National Autonomous University of Mexico) through the project R562

Toxicity and structure-activity relationship (SAR) of α, β-dehydroamino acids against human cancer cell lines

A library of N-protected dehydroamino acids, namely dehydroalanine, dehydroaminobutyric acid and dehydrophenylalanine derivatives, was screened in three human cancer cell lines [(lung (A549), gastric (AGS) and neuroblastoma (SH-SY5Y)] in order to characterize their toxicological profile and identify new molecules with potential anticancer activity. Results showed N-protected dehydrophenylalanine and dehydroaminobutyric acid derivatives have no or low toxicity for all tested cell lines. The N-protected dehydroalanines exhibit significant toxic effects and the AGS and SH-SY5Y cells were significantly more vulnerable than A549 cells. Four α,β- dehydroalanine derivatives, with IC50 < 62.5 μM, were selected to investigate the pathways by which these compounds promote cell death. All compounds, at their IC50 concentrations, were able to induce apoptosis in both AGS and SH-SY5Y cell lines. In both cell lines, loss of mitochondrial membrane potential (ΔΨm) was found and caspase activity was increased, namely endoplasmic reticulum-resident caspase-4 in AGS cells and caspase-3/7 in SH-SY5Y cells. When evaluated in a non-cancer cell line, the molecules displayed no to low toxicity, thus suggesting some degree of selectivity for cancer cells. The results indicate that α,β-dehydroalanine derivatives can be considered a future resource of compounds able to work as anticancer drugs.This work received financial support from National Funds (FCT/MEC) through Project UID/QUI/50006/2013, co-financed by European Union (FEDER under the Partnership Agreement PT2020); and from Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF) (project NORTE-01-0145-FEDER 000024).info:eu-repo/semantics/publishedVersio

Hepatotoxin microcystin-LR extraction optimization

Several cyanobacterial genera produce toxic secondary metabolites, the most well-known of which are the hepatotoxic microcystins (MCYSTs). Microcystin analyses in drinking water are a requirement of the Health Ministry (Regulation 518/2004) in Brazil, but this regulation does not establish which extraction and analytical method should be used; toxin quantification is usually carried out by ELISA (enzyme-linked immunosorbent assay) or HPLC (high performance liquid chromatography), the efficiency of which depends on the extraction method used. In this work a simple, fast and cheap method of extraction was developed for the isolation and identification of MCYSTs. For this, the strain Microcystis aeruginosa NPLJ-4, reported to be a MCYST-LR producer, was selected. Eight different treatments were tested to determine the best MCYST extraction. Samples were applied in LC-MS (liquid chromatography-mass spectrometry), ELISA and Q-TOF (quadrupole time-of-flight). The most efficient extraction was achieved by sonicating samples diluted in water. The proposed method permits rapid sample processing, and establishes an extraction method for both the analysis and identification of MCYST-LR and other variants.Vários gêneros de cianobactérias produzem metabólitos secundários tóxicos, entre eles as hepatotoxinas microcistinas. A análise de microcistinas em águas para abastecimento humano é uma exigência do Ministério da Saúde (Portaria 518/2004), mas essa portaria ainda não estabelece o método de extração e análise a serem usados e a quantificação da toxina é comumente realizada por ELISA ("enzyme-linked immunosorbent assay") ou HPLC (cromatografia líquida de alta eficiência), cuja eficiência depende do método de extração utilizado. Neste trabalho foi desenvolvido um método simples, rápido e barato de extração para o isolamento e identificação de microcistinas. Para isso, selecionou-se a linhagem Microcystis aeruginosa NPLJ-4 descrita como produtora de microcistina-LR. Oito diferentes tratamentos foram testados para determinar a melhor extração da toxina. As amostras foram analisadas por LC-MS (cromatografia líquida acoplada a espectrometria de massas), ELISA e Q-TOF ("quadrupole time-of-flight"). Os resultados mostraram que a melhor extração foi a que usou sonicação das amostras diluídas em água. O método proposto permite o processamento rápido das amostras e estabelece um método de extração para análise e identificação de microcistina-LR e outras variantes.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP

Anti-Inflammatory Effects of 5α,8α-Epidioxycholest-6-en-3β-ol, a Steroidal Endoperoxide Isolated from Aplysia depilans, Based on Bioguided Fractionation and NMR Analysis

[Abstract:] Sea hares of "Aplysia" genus are recognized as a source of a diverse range of metabolites. 5α,8α-Endoperoxides belong to a group of oxidized sterols commonly found in marine organisms and display several bioactivities, including antimicrobial, anti-tumor, and immunomodulatory properties. Herein we report the isolation of 5α,8α-epidioxycholest-6-en-3β-ol (EnP(5,8)) from "Aplysia depilans" Gmelin, based on bioguided fractionation and nuclear magnetic resonance (NMR) analysis, as well as the first disclosure of its anti-inflammatory properties. EnP(5,8) revealed capacity to decrease cellular nitric oxide (NO) levels in RAW 264.7 macrophages treated with lipopolysaccharide (LPS) by downregulation of the Nos2 (inducible nitric oxide synthase, iNOS) gene. Moreover, EnP(5,8) also inhibited the LPS-induced expression of cyclooxygenase-2 (COX-2), interleukin 6 (IL-6), and tumor necrosis factor alpha (TNF-α) at the mRNA and protein levels. Mild selective inhibition of COX-2 enzyme activity was also evidenced. Our findings provide evidence of EnP(5,8) as a potential lead drug molecule for the development of new anti-inflammatory agents.Portugal.Fundação para a Ciência e Tecnologia; UID/QUI/50006/2019Portugal. Fundação para a Ciência e Tecnologia; PD/BD/113565/201

Parametric and machine learning-based analysis of the seismic vulnerability of adobe historical buildings damaged after the September 2017 Mexico earthquakes

In September 2017, two strong earthquakes hit the central region of Mexico, producing substantial damage to the historical buildings. A retroactive analysis for assessing the pre-event seismic vulnerability of these constructions allowed for testing the suitability of an existing parameter-based approach based on material and geometrical features. More than 160 adobe buildings in four municipalities of the State of Morelos were surveyed and included in a vulnerability-oriented GIS database. Data were collected on-site and managed by resorting to open-source GIS software combined with a Python-based database management tool and a cloud-based platform for onsite data collection using mobile devices. The parameter-based approach was used for assessing the analytical seismic vulnerability of the buildings and implementing a secondary, more conservative assessment that considers uncertainties associated with the data acquisition process. The capabilities of the database were further used to train a Machine Learning algorithm aimed at overcoming some representativeness limitations of the parameter-based analytical method. This third approach was found to be suitable for assessing the vulnerability of the building typologies addressed in this investigation. Although the implementation discussed in this paper is limited to a specific vernacular typology, it can be used to conduct customized local calibrations

Relationship between professional motivations and the expectation of staying at the same workplace: a cross-sectional descriptive study with physicians in Portugal

There is a global trend related to the migration of health professionals, particularly physicians, to the most densely populated areas. In Portugal, the unequal distribution of medical professionals is justified by the fact that in the most favoured areas, there are more career opportunities, better infrastructures and equipment, better working conditions and supervision, more and better social facilities and better salary. The aim of this work was to identify professional reasons associated with the expectation of staying at the same workplace. It was selected a simple random sample of 594 physicians out of a total of 18,711 registered physicians in Northern Regional Section of the Order of Physicians (NRSOP), Portugal Most physicians would like to stay at the same workplace due to: the prospect of training and working at the current location, the organizational level of the unit, the level of differentiation of the hospital/health centre, the availability to use the state-of-the-art medical and surgical technology, better rewards, the level of work differentiation in the unit/service, the possibility of reconciling public and private practice, good references of the current unit/working group, avoid unit/workgroup with bad references and the prospect of career progression. This study revealed that, for physicians, professional motivations/purposes have an influence on the expectations of staying or not at the same workplace. Therefore, the study recommends that policy makers should prioritize professional reasons when formulating and implementing measures to promote the fixing of medical professionals in order to achieve greater equity in access to health care.This work is supported by: the European Structural and Investment Funds in the FEDER component, through the Operational Competitiveness and Internationalization Programme (COMPETE 2020) [Project No. 006971 (UID/SOC/04011)]; and national funds, through the FCT – Portuguese Foundation for Science and Technology under the project UID/SOC/04011/2013.info:eu-repo/semantics/publishedVersio