No evidence so far on the protective effect of hydroxychloroquine to prevent COVID-19 : comment by Joob and Wiwanitkit

Copyright © Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ. This article is made freely available for use in accordance with BMJ’s website terms and conditions for the duration of the covid-19 pandemic or until otherwise determined by BMJ. You may use, download and print the article for any lawful, non-commercial purpose (including text and data mining) provided that all copyright notices and trade marks are retained. https://bmj.com/coronavirus/usageWe read with interest the comment by Joob and Wiwanitkit on the letter published by Monti et al in the Annals of the Rheumatic Diseases (ARD). In it, the authors state that there are no reported cases of patients with systemic lupus erythematosus (SLE) with COVID-19 and suggest that this may be due to a protective effect of hydroxychloroquine, a mainstay treatment taken by most patients with SLE. A similar suggestion had already been made earlier this month in the ARD by colleagues from Italy, the first hardly-hit western country, and was reinforced by yet another recently published letter.info:eu-repo/semantics/publishedVersio

Polysaccharides As Viscosupplementation Agents: Structural Molecular Characteristics but Not Rheology Appear Crucial to the Therapeutic Response

IntroductionMost clinical studies and basic research document viscosupplementation (VS) in terms of effectiveness and safety, but only a few highlight its molecular mechanisms of action. Besides, there is generally focus on hyaluronic acid (HA) as being the most relevant polysaccharide to reach the clinical endpoints, attributing its effect mainly to its unique viscoelastic properties, related to a high-molecular weight and gel formulation. Usually, studies do not approach the possible biological pathways where HA may interfere, and there is a lack of reports on other biocompatible polysaccharides that could be of use in VS.AimWe briefly review the main proposed mechanisms of action of intra-articular hyaluronic acid (IA-HA) treatment and discuss its effectiveness focusing on the role of rheological and intrinsic structural molecular properties of polysaccharides in providing a therapeutic effect.MethodsWe conducted a literature search using PubMed database to find articles dealing with the mechanisms of action of IA-HA treatment and/or emphasizing how the structural properties of the polysaccharide used influenced the clinical outcomes.Discussion/conclusionHA is involved in numerous biochemical interactions that may explain the clinical benefits of VS, most of them resulting from HA–cluster of differentiation 44 receptor interaction. There are other important aspects apart from the molecular size or the colloidal state of the IA-HA involved in VS efficiency that still need to be consolidated. Indeed, it seems that clinical response may be dependent on the intrinsic properties of the polysaccharide, regardless of being HA, rather than to rheology, posing some controversy to previous beliefs

An MCDM approach to the selection of novel technologies for innovative in-vehicle information systems

Driving a car is a complex skill that includes interacting with multiple systems inside the vehicle. Today’s challenge in the automotive industry is to produce innovative In-Vehicle Information Systems (IVIS) that are pleasant to use and satisfy the costumers’ needs while, simultaneously, maintaining the delicate balance of primary task vs. secondary tasks while driving. The authors report a MCDM approach for rank ordering a large heterogeneous set of human-machine interaction technologies; the final set consisted of hundred and one candidates. They measured candidate technologies on eight qualitative criteria that were defined by domain experts, using a group decision-making approach. The main objective was ordering alternatives by their decision score, not the selection of one or a small set of them. The authors’ approach assisted decision makers in exploring the characteristics of the most promising technologies and they focused on analyzing the technologies in the top quartile, as measured by their MCDM model. Further, a clustering analysis of the top quartile revealed the presence of important criteria trade-offs.Operational Competitiveness Program – COMPETE, QREN (Quadro de Referência Estratégico Nacional), European Regional Development Funds (European Union), R&D project in joint-promotion (HMIEXCEL-2013-2015 36265/2013) HMIEXCEL - I&D crítica em torno do ciclo de desenvolvimento e produção de soluções multimédia avançadas para automóvelStrategic program FCT-UID/EEA/00066/2013Fundação para a Ciência e a Tecnologia (IF/00217/2013)Fundação para a Ciência e a Tecnologia (PD/BD/105966/2014

Dietary Methionine Improves the European Seabass (Dicentrarchus labrax) Immune Status, Inflammatory Response, and Disease Resistance

Methionine presents a pivotal role in the regulation of many cellular events with crucial impact on the immune system, such as in processes involved in the control of inflammation and polyamines synthesis. Accordingly, the present study aimed to assess the modulatory effects of dietary methionine on the European seabass (Dicentrarchus labrax) immune status, inflammatory response and disease resistance to Photobacterium damselae subsp. piscicida (Phdp). For this purpose, fish were randomly distributed in three independent groups (three replicates per group) and each was fed the corresponding diet: a control diet (CTRL) formulated to meet the established amino acid requirements for the species; a diet supplemented with methionine at 0.5% of feed weight relative to the CTRL diet (8.2% of methionine concentration above CTRL); and one supplemented with methionine at 1% of feed weight to the CTRL diet (11.8% of methionine concentration above CTRL). To evaluate the immune status of fish fed with each of the diets before being submitted to bacterial infection fish were sampled from each group at 2 and 4 weeks after the beginning of feeding. Non-sampled fish were injected intraperitoneally with Phdp (5 × 103 cfu/fish) at 4 weeks after initiation of feeding and the inflammatory response (at 4, 24, and 48 h post-infection) and survival (lasting 21 days post-infection) evaluated. Fish hematological profile, peripheral cell dynamics, plasma humoral immune parameters, leucocyte migration to the inflammatory focus and head-kidney gene expression were evaluated. Results show that methionine dietary supplementation improves seabass cellular immune status without evidence of activation of pro-inflammatory mechanisms. Additionally, the observed enhanced immune status provided by methionine supplementation translated into an improved immune response to infection, as higher cellular differentiation/proliferation and recruitment to the inflammatory focus, improved plasma humoral immune parameters and modulation of key immune-related genes was observed. Lastly, after a bacterial challenge, higher survival was observed in fish fed supplemented diets, ultimately corroborating the positive effect of methionine administration for 4 weeks in the cellular immune status

Chocolate funcional contendo o probiótico Bifidobacterium animalis subespécie lactis BB-12

O chocolate é um dos produtos alimentares mais atrativos para a população e tem sido proposto como um bom vetor para a libertação de probióticos, conhecidos como microrganismos vivos que, quando administrados em quantidades adequadas, conferem benefícios à saúde humana 1,2. Especificamente, a bactéria probiótica Bifidobacterium animalis subespécie lactis BB-12®, originária de uma coleção de culturas lácteas (Chr. Hansen), tem sido associada a efeitos benéficos a nível gastrointestinal e da função imunológica [3]. No presente trabalho, a estirpe probiótica B. animalis subespécie lactis BB-12® foi incorporada em chocolates com três diferentes teores de cacau (33.6%; 54.5% e 70.5%), sendo avaliada a viabilidade ao longo do armazenamento aeróbio a temperatura ambiente (25ºC) por 28 dias. Além disso, cada chocolate incorporando o probiótico foi caracterizado em termos de pH, conteúdo de compostos fenólicos e atividade antioxidante, usando chocolates controlo (sem bactéria) para fins comparativos. Os nossos resultados mostraram que B. animalis subespécie lactis BB-12® incorporada no chocolate com teor de cacau 70.5% apresentou maior viabilidade ao longo do armazenamento. De facto, a viabilidade do probiótico foi mantida em torno de 108 UFC/g, sendo este valor superior ao limite estabelecido de 106 – 107 UFC/g para que um produto probiótico exerça efeitos benéficos. Através da medição de pH, verificou-se que a adição do probiótico não altera os valores em comparação com os chocolates controlo (sem bactéria) e que durante o armazenamento também não existiram oscilações consideráveis, sugerindo que as bactérias se encontram metabolicamente inativas, o que poderá estar relacionado com a manutenção da sua viabilidade ao longo do tempo. Relativamente às análises do conteúdo de compostos fenólicos, verificou-se um aumento de compostos totais com o aumento do teor de cacau na matriz alimentar, embora a adição da bactéria probiótica não interfira com o conteúdo total. Além disso, através da medição da atividade antioxidante observou-se uma tendência crescente com o aumento de teor de cacau. Em conclusão, o nosso estudo mostrou que o chocolate negro, mais especificamente com teor de cacau de 70.5%, pode ser considerado uma potencial e valiosa matriz alimentar veiculando o probiótico B. animalis subespécie lactis BB-12®. Além disso, esta matriz é uma importante fonte de compostos bioativos, nomeadamente compostos fenólicos, que possuem atividade antioxidante comprovada.info:eu-repo/semantics/publishedVersio

Loss to follow-up in registries of rheumatic patients treated with biologics : a potential information bias in assessing pharmacovigilance and efficacy outcomes

© 2001-2021 Sociedade Portuguesa de Reumatologia.Background: The information associated with loss to follow-up (LFU) patients may affect real-world data evaluation of the use of biologics that is not being adequately captured in registries. Methods: We identified all patients(Pts) treated with biologics in our center who had no visits registered for more than 6 months, in the Rheumatic Diseases Portuguese Register, Reuma.pt. We retrieved baseline information from Reuma.pt and from the hospital electronic clinical record. We then performed a telephonic interview to characterize the reasons for LFU at our day care unit. For Pts unable to be contacted by telephone a letter of invitation to an appointment at the hospital was sent. Results: From a total of 794 Ptsregistered in Reuma.pt at our center with active biologic therapy 227 did not have any information registered in the last 6 months. Of this, 36 Pts were on biologic therapy prescribed by other departments and maintained follow-up in these departments. 102 Pts had suspended biologic administration by medical indication and this information was registered in the hospital electronic clinical records but not updated in Reuma.pt. For 89 Pts no information could be retrieved from either the hospital electronic clinical record or Reuma.pt and we classified these Pts as true LFU. 26 of these LFU Pts were being followed up in another Rheumatology center. 26 of the LFU Pts died. 11 Pts had an adverse effect. 4 Pts of the LFU were considering to be in remission. We were not able to contact 15 of the LFU pts. Conclusion: Identifying LFU Pts and clarifying the reason for the loss of data in a register contributes to a better knowledge on strategies to discontinue biologics in stable pts, to a better pharmacovigilance of adverse effects and to more efficiency in data capture by registries. Due to data protection reasons it was impossible to have access to the Pts's death certificates.info:eu-repo/semantics/publishedVersio

Enzyme-assisted release of antioxidant peptides from porphyra dioica conchocelis

peer-reviewedThe conchocelis life cycle stage of P. dioica represents an unexplored source of bioactive compounds. The aim of this study was to generate and characterise, for the first time, hydrolysates of conchocelis using a specific combination of proteases (Prolyve® and Flavourzyme®). Hydrolysate molecular mass distribution and free amino acid contents were assessed, and the antioxidant activity was determined using a range of in vitro assays. The protein content and the total amino acid profiles of conchocelis were also studied. Conchocelis contained ~25% of protein (dry weight basis) and had a complete profile of essential amino acids. Direct sequential enzymatic treatment modified the profile of the generated compounds, increasing the amount of low molecular weight peptides (<1 kDa). There was a significant improvement in the antioxidant activity of the hydrolysates compared with the control (up to 2.5-fold), indicating their potential as a novel source of antioxidant ingredients

Valorizing coffee silverskin based on its phytochemicals and antidiabetic potential: from lab to a pilot scale

This study investigates the possibility of valorizing coffee silverskin through the recovery of its bioactive compounds using a sustainable extraction method that could be industrially applied. For that, aqueous extracts were prepared using ultrasonic-assisted extraction (laboratorial scale) and, for comparison, a scale-up of the process was developed using the Multi-frequency Multimode Modulated technology. A concentration procedure at the pilot scale was also tested. The three types of extracts obtained were characterized regarding caffeine and chlorogenic acids contents, and the effects on intestinal glucose and fructose uptake (including sugar transporters expression) in human intestinal epithelial (Caco-2) cells were ascertained. The phytochemical contents of the extracts prepared at the laboratory and pilot scale were comparable (caffeine: 27.7 vs. 29.6 mg/g freeze-dried extract; 3-, 4-, and 5-caffeoylquinic acids: 0.19 vs. 0.31, 0.15 vs. 0.42, and 1.04 vs. 1.98 mg/g, respectively; 4- and 5- feruloylquinic acids: 0.39 vs. 0.43 and 1.05 vs. 1.32 mg/g, respectively). Slight differences were noticed according to the extracts preparation steps, but in general, all the extracts promoted significant inhibitions of [1,2-3H(N)]-deoxy-D-glucose and 14C-D-fructose uptake, which resulted mainly from a decrease on the facilitative glucose transporter 2 (GLUT2) and sodium-glucose linked transporter 1 (SGLT1) genes expression but not on the expression of the facilitative glucose transporter 5 (GLUT5) gene. Moreover, a synergistic effect of caffeine and 5-caffeoylquinic acid on sugars uptake was found. The results clearly show that the Multi-frequency Multimode Modulated technology is a viable option to be applied at an industrial level to recover bioactive components from silverskin and obtain extracts with antidiabetic potential that could be used to develop functional food products or dietary supplements.The open access publication fee of this paper was funded by the AgriFood XXI I&D&I project (NORTE-01-0145-FEDER-000041) cofinanced by European Regional Development Fund (ERDF) through the NORTE 2020 (Programa Operacional Regional do Norte 2014/2020)

Vírus influenza e bactéria proteolítica co-infectantes em trato respiratório de indivíduos com manifestações respiratórias

A role for proteolytic bacteria in the exacerbation of influenza virus has been shown in natural hosts such as pigs and humans. Four hundred seven samples were collected from the respiratory tract of individuals presenting clinical manifestations, during influenza season (2003-2005) in São Paulo City. The aim of this study was to evaluate the incidence of determined bacteria co-infecting virus in human respiratory tract. Tests, such as bacteriological, immunofluorescence (IF), RT/PCR and hemagglutination (HA) were used for bacterial and viral investigation. Thirty seven (9.09%) positive for influenza virus were screened by IF. The RT/PCR confirmed the presence of influenza virus in these samples. Bacterial and agar casein tests demonstrated that 18 (48.64%) individuals were infected with proteolytic bacteria such as Staphylococcus spp., Streptococcus spp. and Pseudomonas spp. Among these samples, 13 (35.13%) were co-infected with influenza A virus. Influenza type B, co-infecting bacteria were found in five (13.51%) samples. In vitro the S. aureus protease increased the influenza HA titer after contact for 30 min at 25 ºC. Results revealed the occurrence of co-infection with proteolytic bacteria and influenza in the evaluated individuals. This finding corroborates that virus versus bacteria synergism could be able to potentiate respiratory infection, increasing damage to hosts.O papel da bactéria proteolítica na exacerbação do vírus influenza tem sido demonstrado em hospedeiros naturais como porcos e humanos. Foram coletadas 407 amostras do trato respiratório de indivíduos apresentando manifestações clínicas, durante a estação da influenza (2003-2005) na cidade de São Paulo. Este trabalho teve como objetivo avaliar a incidência de determinadas bactérias que junto com vírus co-infectarem o trato respiratório humano. Testes bacteriológicos, e virológicos como imunofluorescência (IF), RT/PCR e hemaglutinação (HA) foram usados nas investigações viral e bacteriana. Pelo teste de IF foram selecionadas trinta e sete (9,09%) amostras positivas para o vírus influenza. A presença do vírus influenza foi confirmada pela técnica de RT/PCR. Pelos testes bacteriológicos e do agar caseina, verificou-se que 18 (48,64%) dos indivíduos foram infectados com bactérias proteolíticas tais como Staphylococcus spp., Streptococcus spp. e Pseudomonas spp. Destas amostras, 13 (35,13%) foram co-infectadas com vírus influenza tipo A, e 5 (13,51%) com influenza tipo B. No experimento in vitro com influenza e S. aureus, detectou-se aumento do título hemaglutinante deste vírus, após contacto de 30 min a 25 ºC. Os resultados obtidos revelaram a ocorrência de co-infecção com bactéria proteolítica e vírus influenza nos indivíduos avaliados. Estes achados corroboram com a investigação do sinergismo, entre bactéria e vírus, que poderia ser capaz de potencializar infecção respiratória, aumentando os riscos aos hospedeiros