Bifurcations from families of periodic solutions in piecewise differential systems

Consider a differential system of the form $$x'=F_0(t,x)+\sum_{i=1}^k \varepsilon^i F_i(t,x)+\varepsilon^{k+1} R(t,x,\varepsilon),$$ where $F_i:\mathbb{S}^1 \times D \to \mathbb{R}^m$ and $R:\mathbb{S}^1 \times D \times (-\varepsilon_0,\varepsilon_0) \to \mathbb{R}^m$ are piecewise $C^{k+1}$ functions and $T$-periodic in the variable $t$. Assuming that the unperturbed system $x'=F_0(t,x)$ has a $d$-dimensional submanifold of periodic solutions with $d<m$, we use the Lyapunov-Schmidt reduction and the averaging theory to study the existence of isolated $T$-periodic solutions of the above differential system

Quadratic systems with an invariant algebraic curve of degree 3 and a Darboux invariant

Let QS be the class of non-degenerate planar quadratic differential systems and QS3 its subclass formed by the systems possessing an invariant cubic f(x, y) = 0. In this article, using the action of the group of real affine transformations and time rescaling on QS, we obtain all the possible normalforms for the quadratic systems in QS3. Working with these normal forms we complete the characterization of the phase portraits in QS3 having a Darboux invariant of the form f(x, y)est, with s ∈ R

Leishmania amazonensis promastigotes in 3D Collagen I culture: an in vitro physiological environment for the study of extracellular matrix and host cell interactions

Leishmania amazonensis is the causative agent of American cutaneous leishmaniasis, an important neglected tropical disease. Once Leishmania amazonensis is inoculated into the human host, promastigotes are exposed to the extracellular matrix (ECM) of the dermis. However, little is known about the interaction between the ECM and Leishmania promastigotes. In this study we established L. amazonensis promastigote culture in a three-dimensional (3D) environment mainly composed of Collagen I (COL I). This 3D culture recreates in vitro some aspects of the human host infection site, enabling the study of the interaction mechanisms of L. amazonensis with the host ECM. Promastigotes exhibited “freeze and run” migration in the 3D COL I matrix, which is completely different from the conventional in vitro swimming mode of migration. Moreover, L. amazonensis promastigotes were able to invade, migrate inside, and remodel the 3D COL I matrix. Promastigote trans-matrix invasion and the freeze and run migration mode were also observed when macrophages were present in the matrix. At least two classes of proteases, metallo- and cysteine proteases, are involved in the 3D COL I matrix degradation caused by Leishmania. Treatment with a mixture of protease inhibitors significantly reduced promastigote invasion and migration through this matrix. Together our results demonstrate that L. amazonensis promastigotes release proteases and actively remodel their 3D environment, facilitating their migration. This raises the possibility that promastigotes actively interact with their 3D environment during the search for their cellular “home”—macrophages. Supporting this hypothesis, promastigotes migrated faster than macrophages in a novel 3D co-culture model

On the periodic solutions of the Milchelson continuous and discontinuous piecewise linear differential system

Applying new results from the averaging theory for continuous and discontinuous differential systems, we study the periodic solutions of two distinct versions of the Michel- son differential system: a Michelson continuous piecewise linear differential system and a Michelson discontinuous piecewise linear differential system. The tools here used can be applied to general nonsmooth differential systems

Development of the Child Brief Neuropsychological Assessment Battery NEUPSILIN-INF

The aim of this study is to present the development process and content validation of Child Brief Neuropsychological Assessment Battery NEUPSILIN-INF, which briefly assesses the components of eight neuropsychological functions in school-aged children: orientation, attention, visual perception, memory, arithmetic abilities, language, visuoconstructive abilities and executive functions. The process comprised: 1) the analysis of the original NEUPSILIN instrument and definition of the functions and tasks to be adapted for the child neuropsychological assessment; 2) the development of new tasks considered as fundamental for the assessment in children; 3) pilot study 1 with the preliminary version of the instrument; 4) analysis by specialist judges; 5) pilot studies 2 and 3, new reformulation of the instrument's tasks and preparation of its final version. The instrument presented appropriate face and content validity.O objetivo deste estudo é apresentar o processo de desenvolvimento e validação de conteúdo do Instrumento de Avaliação Neuropsicológica Breve Infantil NEUPSILIN-INF, que avalia, de modo breve, componentes de oito funções neuropsicológicas em crianças em idade escolar: orientação, atenção, percepção visual, memória, habilidades aritméticas, linguagem, habilidades visuoconstrutivas e funções executivas. O processo envolveu: 1) análise do instrumento original NEUPSILIN e definição das funções e tarefas a serem adaptadas para avaliação neuropsicológica infantil; 2) desenvolvimento de novas tarefas consideradas fundamentais para a avaliação na infância; 3) estudo piloto 1 com a versão preliminar do instrumento; 4) análise de juízes especialistas; 5) estudos piloto 2 e 3, nova reformulação de tarefas do instrumento e elaboração de sua versão final. O instrumento apresentou adequada validade aparente e de conteúdo.Universidade Federal do Rio Grande do SulPontifícia Universidade Católica do Rio Grande do SulUniversidade Presbiteriana MackenzieUniversidade Federal de São Paulo (UNIFESP)UNIFESPSciEL

Globotriaosylceramide is correlated with oxidative stress and inflammation in Fabry patients treated with enzyme replacement therapy

AbstractFabry disease is an X-linked inborn error of glycosphingolipid catabolism due to deficient activity of α-galactosidase A that leads to accumulation of the enzyme substrates, mainly globotriaosylceramide (Gb3), in body fluids and lysosomes of many cell types. Some pathophysiology hypotheses are intimately linked to reactive species production and inflammation, but until this moment there is no in vivo study about it. Hence, the aim of this study was to investigate oxidative stress parameters, pro-inflammatory cytokines and Gb3 levels in Fabry patients under treatment with enzyme replacement therapy (ERT) and finally to establish a possible relation between them. We analyzed urine and blood samples of patients under ERT (n=14) and healthy age-matched controls (n=14). Patients presented decreased levels of antioxidant defenses, assessed by reduced glutathione (GSH), glutathione peroxidase (GPx) activity and increased superoxide dismutase/catalase (SOD/CAT) ratio in erythrocytes. Concerning to the damage to biomolecules (lipids and proteins), we found that plasma levels of malondialdehyde (MDA) and protein carbonyl groups and di-tyrosine (di-Tyr) in urine were increased in patients. The pro-inflammatory cytokines IL-6 and TNF-α were also increased in patients. Urinary Gb3 levels were positively correlated with the plasma levels of IL-6, carbonyl groups and MDA. IL-6 levels were directly correlated with di-Tyr and inversely correlated with GPx activity. This data suggest that pro-inflammatory and pro-oxidant states occur, are correlated and seem to be induced by Gb3 in Fabry patients

Use of epidermic and granulocyte-colony stimulating growth factors in the prevention and treatment of necrotizing enterocolitis of the newborn

OBJETIVO: Revisar os conhecimentos existentes em relação ao uso de fatores de crescimento epidérmico e estimulador de colônias de granulócitos na prevenção e/ou no tratamento da enterocolite necrosante (ECN) durante o período neonatal. FONTES DE DADOS: Revisão da literatura, nas bases de dados Medline, Lilacs, SciELO e PubMed, utilizando os unitermos "recém-nascidos", "enterocolite" e "fatores de crescimento", no período de 2003 a 2007. Nesta busca, 49 artigos foram encontrados, sendo 17 pertinentes ao tema. Também foram utilizados outros artigos, independente do ano de publicação, relacionados a aspectos definidores da ECN no recém-nascido. SÍNTESE DOS DADOS: A ECN continua sendo responsável por uma elevada morbimortalidade neonatal. Os mecanismos fisiopatológicos vêm sendo elucidados e, a partir deles, são discutidas novas terapias, como o uso de fatores de crescimento, destacando-se o fator de crescimento epidérmico e o fator estimulador de colônias de granulócitos. CONCLUSÕES: O uso de fatores de crescimento no tratamento e prevenção da ECN neonatal parece promissor. É necessário maior número de ensaios clínicos para comprovar sua eficácia e segurança. Enquanto isso, a melhor prática médica continua sendo a prevenção da doença.OBJECTIVE: To review the literature regarding the use of hematopoietic and epidermic growth factors for prevention or treatment of neonatal necrotizing enterocolitis (NEC). DATA SOURCES: Literature review of Medline, Lilacs, SciELO and Pubmed databases, using the key-words "newborn", "enterocolitis" and "growth factors", from 2003 to 2007. Fourty-nine papers were retrieved, but only 17 related to the subject. Other studies that described some clinical aspects of enterocolitis were also included, regardless of the year of publication. DATA SYNTHESIS: Necrotizing and enterocolitis has been an important cause of morbidity and mortality in the neonatal period. As the knowledge about the pathophysiology of this disease improves, new therapies, such as the administration of epidermal growth factor and granulocyte colony-stimulating factor, are being discussed. CONCLUSIONS: The use of growth factors for treatment and prevention of NEC seems promising. However, further clinics assays are needed to evaluate the effectiveness and the safety of these growth factors. At this moment, the best clinical practice is the prevention of the disease

Trypsin-like serine peptidase profiles in the egg, larval, and pupal stages of Aedes albopictus

BACKGROUND: Aedes albopictus, a ubiquitous mosquito, is one of the main vectors of dengue and yellow fever, representing an important threat to public health worldwide. Peptidases play key roles in processes such as digestion, oogenesis, and metamorphosis of insects. However, most of the information on the proteolytic enzymes of mosquitoes is derived from insects in the adult stages and is often directed towards the understanding of blood digestion. The aim of this study was to investigate the expression of active peptidases from the preimaginal stages of Ae. albopictus. METHODS: Ae. albopictus eggs, larvae, and pupae were analyzed using zymography with susbtrate-SDS-PAGE. The pH, temperature and peptidase inhibitor sensitivity was evaluated. In addition, the proteolytic activities of larval instars were assayed using the fluorogenic substrate Z-Phe-Arg-AMC. RESULTS: The proteolytic profile of the larval stage was composed of 8 bands ranging from 17 to 130 kDa. These enzymes displayed activity in a broad range of pH values, from 5.5 to 10.0. The enzymatic profile of the eggs was similar to that of the larvae, although the proteolytic bands of the eggs showed lower intensities. The pupal stage showed a complex proteolytic pattern, with at least 6 bands with apparent molecular masses ranging from 30 to 150 kDa and optimal activity at pH 7.5. Peptidases from larval instars were active from 10°C to 60°C, with optimal activity at temperatures between 37°C and 50°C. The proteolytic profile of both the larval and pupal stages was inhibited by phenyl-methyl sulfonyl-fluoride (PMSF) and Nα-Tosyl L-lysine chloromethyl ketone hydrochloride (TLCK), indicating that the main peptidases expressed during these developmental stages are trypsin-like serine peptidases. CONCLUSION: The preimaginal stages of Ae. albopictus exhibited a complex profile of trypsin-like serine peptidase activities. A comparative analysis of the active peptidase profiles revealed differential expression of trypsin-like isoforms among the preimaginal stages, suggesting that some of these enzymes are stage specific. Additionally, a comparison of the peptidase expression between larvae from eggs collected in the natural environment and larvae obtained from the eggs of female mosquitoes maintained in colonies for a long period of time demonstrated that the proteolytic profile is invariable under such conditions

Nanopharmaceuticals for eye administration: sterilization, depyrogenation and clinical applications

As an immune-privileged target organ, the eyes have important superficial and internal barriers, protecting them from physical and chemical damage from exogenous and/or endogenous origins that would cause injury to visual acuity or even vision loss. These anatomic, physiological and histologic barriers are thus a challenge for drug access and entry into the eye. Novel therapeutic concepts are highly desirable for eye treatment. The design of an efficient ocular drug delivery system still remains a challenge. Although nanotechnology may offer the ability to detect and treat eye diseases, successful treatment approaches are still in demand. The growing interest in nanopharmaceuticals offers the opportunity to improve ophthalmic treatments. Besides their size, which needs to be critically monitored, nanopharmaceuticals for ophthalmic applications have to be produced under sterilized conditions. In this work, we have revised the different sterilization and depyrogenation methods for ophthalmic nanopharmaceuticals with their merits and drawbacks. The paper also describes clinical sterilization of drugs and the outcomes of inappropriate practices, while recent applications of nanopharmaceuticals for ocular drug delivery are also addressed.The authors acknowledge the sponsorship received from the Portuguese Science and Technology Foundation, Ministry of Science and Education (FCT/MEC) through national funds, co-financed by FEDER, under the Partnership Agreement PT2020 for the project UIDB/04469/2020 (strategic fund) granted to EBS, the National Council for Scientific and Technological Development (CNPq), Brazil, for the project 425271/2016-1 granted to M.V.C., and the Coordenação Aperfeiçoamento de Pessoal de Nivel Superior (CAPES) and Fundação de Ámparo à Pesquisa do Estado de Sergipe (FAPITEC) (88887.159533/2017-00), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq301964/2019-0 Chamada 06/2019, and Chamada CNPq nº 01/2019), granted to P.S.info:eu-repo/semantics/publishedVersio

Jogos digitais na estimulação cognitiva em idosos: resultados preliminares sobre a função mnemônica

O envelhecimento populacional é uma realidade na sociedade brasileira. Diante desse cenário, faz-se necessário investir em atividades de estimulação cognitiva para esse segmento populacional, uma vez que a idade é um fator de risco para o aparecimento de déficits em tais habilidades. Neste sentido, o presente artigo tem como objetivo apresentar uma pesquisa realizada com 14 idosos frequentadores de uma Universidade da Terceira Idade que participaram de uma intervenção mediada por jogos digitais. Foi analisado o desempenho qualitativo e quantitativo dos participantes em relação aos jogos, bem como o desempenho cognitivo, por meio de testes e tarefas que avaliam a função de memória. Os resultados apontam que os participantes ficaram abaixo das médias nas atividades de fluência verbal e na atividade de memória das Figuras Complexas de Reys e dentro da média em relação ao desempenho no Teste de Aprendizagem Auditivo-visual de Rey e do Mini Exame do Estado Mental, indicando que essa é uma função que necessita de investigação acerca das atividades de estimulação. As atividades com jogos, por sua vez, apontam que os participantes apresentaram melhora no desempenho ao longo das interações, indicados pela diminuição no tempo e pelo aumento das pontuações, o que pode indicar incremento no desempenho da função mnemônica