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O presente documento constitui-se numa prática de reflexões e cruzamentos, através da qual resgato uma pluralidade de olhares que se dão no entorno da minha relação com a escola e com o ensino da Educação Visual - num determinado tempo e espaço -, os mesmos que condicionaram o meu olhar durante a prática do estágio. Ambas, práticas que pretendem colocar em causa os rituais nos quais se inscreve esta disciplina do 3º ciclo do ensino básico, e que a condicionam. Deste modo, tento traçar uma breve linha de análise sobre a forma como o sistema escolar, e o tipo particular de educação artística que dele resulta, têm vindo, às mãos das vontades políticas, a consolidar-se enquanto lugar de prescrição, de produção e de classificação, atendendo a uma missão normalizadora que não só governa a subjetividade individual - tanto dos alunos como dos professores - dentro do contexto da sala de aula, como fabrica uma percepção específica - e coletiva - da própria disciplina de EV. Um, então, conjunto de olhares, de quem se encontra na fronteira entre o aluno e o professor, que pretende questionar o papel prescindível que a educação visual tem vindo a preservar, progressivamente, não só no processo educativo dos alunos assim como no ensino artístico em geral.

To evaluate the association of genetic polymorphisms of vitamin D transporter protein (A total of 383 individuals were studied, considering the total group (TotalG) of patients with cirrhosis (TotalG

Background Cell-penetrating peptides (CPPs) have been extensively exploited in gene therapy approaches as vectors for intracellular delivery of bioactive molecules. The ability of CPPs to be internalized into cells and their capacity to complex nucleic acids depend on their molecular structure, both primary and secondary, namely regarding hydrophobicity/hydrophilicity. CPP acylation has been used as a strategy to improve this structural feature. Methods Acyl groups (from 6 to 18 carbon atoms) were attached to the S413-PV peptide and their effects on the peptide competence to complex siRNAs and to mediate gene silencing in glioblastoma (GBM) cells were studied. A systematic characterization of membrane interactions with S413-PV acyl-derivatives was also conducted, using different biophysical techniques (surface pressure-area isotherms in Langmuir monolayers, DSC and 31P NMR) to unravel a relationship between CPP biological activity and CPP effects on membrane stability and lipid organization. Results A remarkable concordance was noticed between acylated-S413-PV peptide competence to promote gene silencing in GBM cells and disturbance induced in membrane models, the lauroyl- and myristoyl-S413-PV peptides being the most effective. A cut-off effect was described for the first time regarding the influence of acyl-chain length on CPP bioactivity. Conclusions C12-S413-PV showed high capacity to destabilize lipid bilayers, to escape from lysosomal degradation and to mediate gene silencing without promoting cytotoxicity. General significance Besides unraveling a new CPP with high potential to be employed as a gene delivery vector, this work emphasizes the benefit from allying biophysical and biological studies towards a proper CPP structural refinement for successful pre-clinical/clinical application.

Conjugation of TP10, a cell-penetrating peptide with intrinsic antimalarial activity, to the well-known antimalarial drugs chloroquine and primaquine has been previously shown to enhance the peptide&rsquo, s action against, respectively, blood- and liver-stage malaria parasites. Yet, this was achieved at the cost of a significant increase in haemolytic activity, as fluorescence microscopy and flow cytometry studies showed the conjugates to be more haemolytic for non-infected than for Plasmodium-infected red blood cells. To gain further insight into how these conjugates distinctively bind, and likely disrupt, membranes of both Plasmodium-infected and non-infected erythrocytes, we used dynamic light scattering and surface plasmon resonance to study the interactions of two representative conjugates and their parent compounds with lipid model membranes. Results obtained are herein reported and confirm that a strong membrane-disruptive character underlies the haemolytic properties of these conjugates, thus hampering their ability to exert selective antimalarial action.

PurposeThis study aimed to endow the cell-penetrating peptide (CPP) S4(13)-PV with adequate features towards a safe and effective application in cancer gene therapy.MethodsPeptide/siRNA complexes were prepared with two new derivatives of the CPP S4(13)-PV, which combine a lauroyl group attached to the N- or C-terminus with a histidine-enrichment in the N-terminus of the S4(13)-PV peptide, being named C12-H-5-S4(13)-PV and H-5-S4(13)-PV-C12, respectively. Physicochemical characterization of siRNA complexes was performed and their cytotoxicity and efficiency to mediate siRNA delivery and gene silencing in cancer cells were assessed in the absence and presence of serum.ResultsPeptide/siRNA complexes prepared with the C12-H-5-S4(13)-PV derivative showed a nanoscale (ca. 100 nm) particle size, as revealed by TEM, and efficiently mediated gene silencing (37%) in human U87 glioblastoma cells in the presence of 30% serum. In addition, the new C12-H-5-S4(13)-PV-based siRNA delivery system efficiently downregulated stearoyl-CoA desaturase-1, a key-enzyme of lipid metabolism overexpressed in cancer, which resulted in a significant decrease in the viability of U87 cells. Importantly, these complexes were able to spare healthy human astrocytes.ConclusionsThese encouraging results pave the way for a potential application of the C12-H-5-S4(13)-PV peptide as a promising tool in cancer gene therapy. European Regional Development Fund (ERDF), through the Centro 2020 Regional Operational Programme [CENTRO-010145-FEDER-000008] European Regional Development Fund (ERDF), through the COMPETE 2020 -Operational Programme for Competitiveness and Internationalisation Portuguese national funds via FCT - Fundacao para a Ciencia e a Tecnologia [POCI-01-0145-FEDER-016390: CANCEL STEM, POCI-01-0145-FEDER-007440, UIDB/04539/2020] Fundacao para a Ciencia e Tecnologia (FCT, Portugal)Portuguese Foundation for Science and Technology [UID/QUI/50006/2013, UID/MULTI/04378/2013, IF/00092/2014, SFRH/BD/79077/2011, PD/BD/106035/2015] info:eu-repo/semantics/publishedVersion

This study aimed to endow the cell-penetrating peptide (CPP) S4Peptide/siRNA complexes were prepared with two new derivatives of the CPP S4Peptide/siRNA complexes prepared with the C12-HThese encouraging results pave the way for a potential application of the C12-H

Introduction Chronic subdural hematoma (CSH) is one of the most frequent forms of intracranial hemorrhage. It is a collection of encapsulated, well-delimited fluid and/or coagulated blood in several clotting stages located between the dura mater and the arachnoid mater. Objective To describe the epidemiological aspects of CSH described in the database of the Brazilian Unified Health System (SUS, in the Portuguese acronym) regarding admission numbers, hospitalization expenses, health care professional expenses, mortality rate, and death numbers by region from 2008 to the first half of 2016. Methods The present work was performed between August and September 2016 with a review about the epidemiological aspects of CSH in Brazil according to the Informatics Department of the Unified Health System (DATASUS) database, encompassing the period from January 2008 to June 2016, and to scientific papers from the past 10 years which were electronically published at the PubMed, Scielo, and LILACS databases. Results From 2008 to the first half of 2016, the total values were the following: hospital admission authorizations (HAAs). 33,878; hospital expenses, BRL 65,909,429.22; health care professional expenses, BRL 25,158,683.21; deaths, 2,758; and mortality rates ranging from 6.47 to 12.63%. Conclusion In spite of the high clinical relevance of CSH, epidemiological studies about this condition are limited. As such, the present paper is an updated approach on CSH, focusing on its epidemiological aspects according to the DATASUS database.

Recently, we disclosed primaquine cell penetrating peptide conjugates that were more potent than parent primaquine against liver stage Plasmodium parasites and non-toxic to hepatocytes. The same strategy was now applied to the blood-stage antimalarial chloroquine, using a wide set of peptides, including TP10, a cell penetrating peptide with intrinsic antiplasmodial activity. Chloroquine-TP10 conjugates displaying higher antiplasmodial activity than the parent TP10 peptide were identified, at the cost of an increased hemolytic activity, which was further confirmed for their primaquine analogues. Fluorescence microscopy and flow cytometry suggest that these drug-peptide conjugates strongly bind, and likely destroy, erythrocyte membranes. Taken together, the results herein reported put forward that coupling antimalarial aminoquinolines to cell penetrating peptides delivers hemolytic conjugates. Hence, despite their widely reported advantages as carriers for many different types of cargo, from small drugs to biomacromolecules, cell penetrating peptides seem unsuitable for safe intracellular delivery of antimalarial aminoquinolines due to hemolysis issues. This highlights the relevance of paying attention to hemolytic effects of cell penetrating peptide-drug conjugates. This research was funded by Fundação para a Ciência e Tecnologia (FCT), Portugal, grants UID/QUI/50006/2019, IF/00092/2014/CP1255/CT0004, and PD/BD/106035/2015 and Ministerio de Ciencia, Innovación y Universidades, Spain, grant RTI2018-094579-B-I00 (which included FEDER funds).

This journal is © The Royal Society of Chemistry 2018, Novel primaquine-cell penetrating peptide conjugates were synthesised and tested in vitro against liver stage Plasmodium berghei parasites. Generally, the conjugates were more active than the parent peptides and, in some cases, than the parent drug. These are unprecedented findings that may open a new route towards antimalarial drug rescuing., The authors are indebted to Fundação para a Ciência e Tecnologia (FCT, Portugal) for funding LAQV-REQUIMTE re- search unit through project UID/QUI/50006/2013. NV thanks FCT and FEDER (European Union) for funding project IF/00092/2014/CP1255/CT0004 and IF position. LA thanks FCT and the Medicinal Biochemistry and Biochemistry International Doctoral Programme (M2B-PhD) for PhD grant PD/BD/106035/2015.

Cell-penetrating peptides (CPPs) have been extensively exploited in gene therapy approaches as vectors for intracellular delivery of bioactive molecules. The ability of CPPs to be internalized into cells and their capacity to complex nucleic acids depend on their molecular structure, both primary and secondary, namely regarding hydrophobicity/hydrophilicity. CPP acylation has been used as a strategy to improve this structural feature.Acyl groups (from 6 to 18 carbon atoms) were attached to the S4A remarkable concordance was noticed between acylated-S4C12-S4Besides unraveling a new CPP with high potential to be employed as a gene delivery vector, this work emphasizes the benefit from allying biophysical and biological studies towards a proper CPP structural refinement for successful pre-clinical/clinical application.

INTRODUÇÃO: Embora os efeitos benéficos do tratamento com análogos de GnRH (GnRHa) na puberdade precoce central (PPC) estejam estabelecidos, aspectos clínicos podem variar em função do grupo racial. OBJETIVO E MÉTODOS: Descrever o perfil de 175 meninas com PPC idiopática tratadas com GnRHa na Bahia, Brasil. RESULTADOS: Houve predomínio do grupo racial mulato (73,6%). A puberdade iniciou-se aos 6,3 ± 0,1 anos. Ao diagnóstico, as crianças apresentavam estatura de 2,2 ± 0,1 DP e índice de massa corpórea (IMC) de 1,5 ± 0,1 DP (> 2 DP em 32%), estando este, inversamente associado (R= -0,20, p= 0,008) à idade no início da puberdade. As idades cronológica e óssea foram de 8,4 ± 0,1 anos e 10,3 ± 0,1 anos, respectivamente, ao início do tratamento. No seu término (n= 52), idade, IMC e estatura (n= 52) foram 10,6 ± 0,1 anos, 1,6 ± 0,2 DP e 1,9 ± 0,2 DP, respectivamente. CONCLUSÃO: Apresentação clínica e evolução puberal foram similares a outros estudos, independente do grupo racial. O tratamento com GnRHa não resultou em ganho de peso significativo na amostra estudada.

UNLABELLED Data concerning the effects of GnRHa on weight gain are scarce. OBJECTIVE To assess the variation of the body mass index (BMI) in girls during GnRHa treatment for idiopathic central precocious puberty (CPP). PATIENTS AND METHODS Semestral anthropometric data from 176 girls treated with goserelin or leuprorelin were analyzed. RESULTS BMI z-score increased from 1.5 +/- 0.1 SD before treatment (n = 176) to 1.7 +/- 0.2 SD after 24 months (n = 61, p = 0.008). In girls with normal weight before treatment, this variation was greater (n = 112, 0.2 +/- 0.1 SD, p = 0.01) than in those who were overweight (n = 63, -0.9 +/- 0.2 SD, p = 0.7). In the goserelin group the weight change adjusted for bone age was greater (n = 28, 0.4 +/- 0.1 SD) than in the leuprorelin group (n = 5, 0.04 +/- 0.1 SD, p = 0.05). CONCLUSIONS A slight increase in BMI was noted, mainly in girls with normal weight before treatment. The influence of different GnRHa on weight must be further investigated.

Although the therapeutic effects of GnRH analogues (GnRHa) in central precocious puberty (CPP) have been established, clinical aspects may vary according to racial groups.To describe the profile of 175 girls from Bahia, Brazil, treated with GnRHa for idiopathic CPP.The mulatto racial group predominated in the sample. The chronological age at puberty was 6.3 +/- 0.1 years. At diagnosis, height was 2.2 +/- 0.1 SD and body mass index (BMI) was 1.5 +/- 0.1 SD (2 SD in 32%), this one, inversely associated with age at onset of puberty (R = -0.20, p = 0.008). At treatment, chronological and bone ages were 8.4 +/- 0.1 years and 10.3 +/- 0.1 years, respectively. At the end of treatment (n = 52) age, BMI and height were 10.6 +/- 0.1 years, 1.6 +/- 0.2 SD and 1.9 +/- 0.2 SD, respectively.Clinical presentation and evolution were similar to other studies, independently of racial characteristics. In this sample, treatment with GnRHa was not associated to significant weight gain.