State-of-the-art polymeric nanoparticles as promising therapeutic tools against human bacterial infections

Infectious diseases kill over 17 million people a year, among which bacterial infections stand out. From all the bacterial infections, tuberculosis, diarrhoea, meningitis, pneumonia, sexual transmission diseases and nosocomial infections are the most severe bacterial infections, which affect millions of people worldwide. Moreover, the indiscriminate use of antibiotic drugs in the last decades has triggered an increasing multiple resistance towards these drugs, which represent a serious global socioeconomic and public health risk. It is estimated that 33,000 and 35,000 people die yearly in Europe and the United States, respectively, as a direct result of antimicrobial resistance. For all these reasons, there is an emerging need to find novel alternatives to overcome these issues and reduced the morbidity and mortality associated to bacterial infectious diseases. In that sense, nanotechnological approaches, especially smart polymeric nanoparticles, has wrought a revolution in this field, providing an innovative therapeutic alternative able to improve the limitations encountered in available treatments and capable to be effective by theirselves. In this review, we examine the current status of most dangerous human infections, together with an in-depth discussion of the role of nanomedicine to overcome the current disadvantages, and specifically the most recent and innovative studies involving polymeric nanoparticles against most common bacterial infections of the human body.Authors acknowledge the support of the Spanish Ministry of Economy and Competitiveness (SAF2017-84283-R and RTI2018-098641-B-I00), Biomedical Research Networking Centre in Neurodegenerative Diseases (CIBERNED, CB06/05/0024), Scientifc Project Marató TV3 (ref 201829-10) and European Regional Development Founds. Authors also acknowledge the Portuguese Science and Technology Foundation (FCT) for the strategic fund (UIDB/04469/2020).info:eu-repo/semantics/publishedVersio

Development of lactoferrin-loaded liposomes for the management of dry eye disease and ocular inflammation

Dry eye disease (DED) is a high prevalent multifactorial disease characterized by a lack of homeostasis of the tear film which causes ocular surface inflammation, soreness, and visual disturbance. Conventional ophthalmic treatments present limitations such as low bioavailability and side effects. Lactoferrin (LF) constitutes a promising therapeutic tool, but its poor aqueous stability and high nasolacrimal duct drainage hinder its potential efficacy. In this study, we incorporate lactoferrin into hyaluronic acid coated liposomes by the lipid film method, followed by high pressure homogenization. Pharmacokinetic and pharmacodynamic profiles were evaluated in vitro and ex vivo. Cytotoxicity and ocular tolerance were assayed both in vitro and in vivo using New Zealand rabbits, as well as dry eye and anti-inflammatory treatments. LF loaded liposomes showed an average size of 90 nm, monomodal population, positive surface charge and a high molecular weight protein encapsulation of 53%. Biopharmaceutical behaviour was enhanced by the nanocarrier, and any cytotoxic effect was studied in human corneal epithelial cells. Developed liposomes revealed the ability to reverse dry eye symptoms and possess anti-inflammatory efficacy, without inducing ocular irritation. Hence, lactoferrin loaded liposomes could offer an innovative nanotechnological tool as suitable approach in the treatment of DED.FCT -Fundação para a Ciência e a Tecnologia(2017SGR1477)info:eu-repo/semantics/publishedVersio

Metal-based nanoparticles as antimicrobial agents: an overview

Metal-based nanoparticles have been extensively investigated for a set of biomedical applications. According to the World Health Organization, in addition to their reduced size and selectivity for bacteria, metal-based nanoparticles have also proved to be effective against pathogens listed as a priority. Metal-based nanoparticles are known to have non-specific bacterial toxicity mechanisms (they do not bind to a specific receptor in the bacterial cell) which not only makes the development of resistance by bacteria difficult, but also broadens the spectrum of antibacterial activity. As a result, a large majority of metal-based nanoparticles efficacy studies performed so far have shown promising results in both Gram-positive and Gram-negative bacteria. The aim of this review has been a comprehensive discussion of the state of the art on the use of the most relevant types of metal nanoparticles employed as antimicrobial agents. A special emphasis to silver nanoparticles is given, while others (e.g., gold, zinc oxide, copper, and copper oxide nanoparticles) commonly used in antibiotherapy are also reviewed. The novelty of this review relies on the comparative discussion of the different types of metal nanoparticles, their production methods, physicochemical characterization, and pharmacokinetics together with the toxicological risk encountered with the use of different types of nanoparticles as antimicrobial agents. Their added-value in the development of alternative, more effective antibiotics against multi-resistant Gram-negative bacteria has been highlighted.M.L.G., M.E. (Miren Ettcheto), A.C., and E.S.L. belong to 2017SGR-1477. E.S.-L., A.C., M.E. (Marta Espina), and M.L.G. acknowledge the support of Institute of Nanoscience and Nanotechnology (ART2018 project). E.B.S. wants to acknowledge the Portuguese Science and Technology Foundation (FCT/MCT) and European Funds (PRODER/COMPETE) for the projects M-ERA-NET-0004/2015-PAIRED and UIDB/04469/2020, co-funded by FEDER, under the partnership Agreement PT2020.info:eu-repo/semantics/publishedVersio

APLICAÇÃO DE TESTES DE NORMALIDADE EM PUBLICAÇÕES NACIONAIS: LEVANTAMENTO BIBLIOGRÁFICO

O objetivo do presente estudo foi investigar e identificar os artigos publicados em periódicos nacionais que aplicaram testes de normalidade, quais os mais utilizados, se há relação com o Qualis e se no decorrer dos anos há um aumento na utilização desses testes. Para elaboração da pesquisa foram escolhidos três periódicos nacionais indexados no SciELO. Foram analisadas publicações entre 2008 e 2012. A análise descritiva foi realizada no Excel 2007 e o teste de normalidade (Shapiro Wilk) pelo SPSS, assim como a comparação entre grupos (ANOVA one way), com nível de significância de 5%. Dentre a totalidade dos Artigos Originais (n=871), foi observado que 358 citaram a utilização de teste de normalidade. Em suma, pode-se afirmar que a Revista Brasileira de Fisioterapia é responsável por 46% dessas publicações. A Revista Fisioterapia e Pesquisa e Revista Fisioterapia em Movimento são responsáveis por 30,2% e 23,7% das publicações, respectivamente. Os testes estatísticos mais utilizados foram Shapiro-Wilk (n=163) e Komolgorov-Smirnov (n=137). Estes foram responsáveis por 83,8% das publicações que citaram testar a normalidade de seus dados. Ainda, 2,8% executaram outros testes e 13,4% não especificaram qual teste utilizado, porém, afirmaram testar a normalidade. Conclui-se então que o periódico nacional de maior Qualis, a Revista Brasileira de Fisioterapia, possui maior rigor criterioso em relação à análise estatística e que não há diferença estatisticamente significante no número de artigos publicados que aplicaram o teste de normalidade no decorrer dos anos. Observa-se também que o teste de Shapiro-Wilk foi o mais utilizado nas publicações

A INFLUÊNCIA DO INTERVALO DE DESCANSO ENTRE A REPETIÇÃO DE UM TESTE DE RESISTÊNCIA MUSCULAR LOCALIZADA EM DUAS DIFERENTES FERRAMENTAS

O objetivo deste estudo foi verificar a porcentagem de indivíduos recuperados passados cinco minutos após a realização de teste de resistência a fadiga em duas diferentes ferramentas. Amostra foi composta por 13 participantes, submetidos a um teste de resistência muscular localizada em dois dias, com intervalo de sete dias entre eles. O teste foi realizado no tubo elástico e no dinamômetro isocinético, caracterizando um estudo cross over. No tubo elástico 84,6% dos participantes se recuperaram no intervalo de cinco minutos em ambos os dias de teste. No dinamômetro isocinético o primeiro dia de teste teve 69,2% dos participantes recuperados. Enquanto que no segunda dia de teste, o percentual de participantes recuperados atingiu valor de 76,9%. Como conclusão, verificou-se que maior percentual de indivíduos se recuperam após realizarem o teste de resistência muscular localizada a fadiga no tubo elástico, porém tais diferenças não foram significantes, que pode ser justificada pelo tamanho da amostra. Por fim, pode-se concluir que cinco minutos seja suficiente para recuperar indivíduos fisicamente ativos

Methodological validation of a vertical ladder with low intensity shock stimulus for resistance training in C57BL/6 mice: Effects on muscle mass and strength, body composition, and lactate plasma levels

The objective of this study was to evaluate the effects of a vertical ladder device for resistance exercises with or without electrical shock stimulus on muscle strength, body composition, limb volume, muscle fibres and plasma lactate and glycemia of female mice. This device is represented by a vertical ladder with electrostimulation. It was analysed in groups of C57BL/6 mice practicing spontaneous physical activity in enriched environment, practicing resisted climbing exercises, practicing resistance exercises with the utility model in question and controls. The acute effects of blood lactate and dark light-box behaviour, and the short-term chronic effects of muscle strength, limb volume, body composition, muscle fibre area, and central and light-dark quantification were verified. According to the findings, the vertical electrostimulation ladder model presented acute effects on lactate levels, similar to other experimental models of resistance exercise and physical activity. The behaviour in the light-dark box test showed no difference between the groups. Regarding the short-term chronic response, the best results were obtained in the impact-stimulated resistive exercise in the limb traction muscle variables, greater brown adipose tissue weight, greater quadriceps femoral muscle structure, limb and greater weight number of nuclei in the skeletal striated muscle fibres. The use of the prototype showed similarities in the acute and chronic adaptations expected in resistance training. However, new study proposals should be encouraged, as the data presented here are the first notes on the use of this utility model.We would like to thank the Foundation for Research Support of the Minas Gerais State (FAPEMIG; grant numbers: PPM-00029-17 and DEG-00010-16); National Council for Scientific and Technological Development (CNPq, grant number: 150038/2017-8 and 430759/2016-9); and the Coordination of Improvement of Higher Education Personnel (CAPES) for the support to carry out this study. AMB De-Paula is research productivity fellow of the CNPq

Coinfection with Different Trypanosoma cruzi Strains Interferes with the Host Immune Response to Infection

A century after the discovery of Trypanosoma cruzi in a child living in Lassance, Minas Gerais, Brazil in 1909, many uncertainties remain with respect to factors determining the pathogenesis of Chagas disease (CD). Herein, we simultaneously investigate the contribution of both host and parasite factors during acute phase of infection in BALB/c mice infected with the JG and/or CL Brener T. cruzi strains. JG single infected mice presented reduced parasitemia and heart parasitism, no mortality, levels of pro-inflammatory mediators (TNF-α, CCL2, IL-6 and IFN-γ) similar to those found among naïve animals and no clinical manifestations of disease. On the other hand, CL Brener single infected mice presented higher parasitemia and heart parasitism, as well as an increased systemic release of pro-inflammatory mediators and higher mortality probably due to a toxic shock-like systemic inflammatory response. Interestingly, coinfection with JG and CL Brener strains resulted in intermediate parasitemia, heart parasitism and mortality. This was accompanied by an increase in the systemic release of IL-10 with a parallel increase in the number of MAC-3+ and CD4+ T spleen cells expressing IL-10. Therefore, the endogenous production of IL-10 elicited by coinfection seems to be crucial to counterregulate the potentially lethal effects triggered by systemic release of pro-inflammatory mediators induced by CL Brener single infection. In conclusion, our results suggest that the composition of the infecting parasite population plays a role in the host response to T. cruzi in determining the severity of the disease in experimentally infected BALB/c mice. The combination of JG and CL Brener was able to trigger both protective inflammatory immunity and regulatory immune mechanisms that attenuate damage caused by inflammation and disease severity in BALB/c mice

A importância do consumo de probióticos e prebióticos para a saúde: uma revisão / The importance of consuming probiotics and prebiotics for health: a review

A sociedade cada vez mais tem buscado adquirir hábitos alimentares mais adequados. Nesta perspectiva, os alimentos funcionais tem um papel relevante por promoverem benefícios adicionais à saúde além de suas atribuições nutricionais básicas, dentre estes alimentos estão os probióticos e os prebióticos. Sendo assim, o objetivo do estudo foi identificar evidências disponíveis na literatura acerca da importância do consumo de probióticos e prebióticos para a saúde. Para tanto, foi realizada uma revisão integrativa de literatura, utilizando artigos científicos completos, no idioma português, com dimensão temporal entre 2015 e 2019. Após o refinamento das publicações científicas conforme os critérios de inclusão obtiveram-se dois artigos, os quais evidenciaram que os probióticos apresentam benefícios na formação e função da microbiota intestinal humana e os prebióticos são capazes de inibir a proliferação de microrganismos patogênicos, além disso, o consumo de probióticos e prebióticos modula o perfil inflamatório e atua frente a várias situações clínicas como: doenças gastrointestinais, diabetes mellitus tipo1, doenças cardiovasculares e obesidade. No entanto, faz-se necessário o desenvolvimento de um maior número de estudos a nível nacional que possam versar sobre as vantagens da utilização destes componentes alimentares

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear un derstanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5–7 vast areas of the tropics remain understudied.8–11 In the American tropics, Amazonia stands out as the world’s most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepre sented in biodiversity databases.13–15 To worsen this situation, human-induced modifications16,17 may elim inate pieces of the Amazon’s biodiversity puzzle before we can use them to understand how ecological com munities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple or ganism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region’s vulnerability to environmental change. 15%–18% of the most ne glected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lostinfo:eu-repo/semantics/publishedVersio