The use of cannabinoids in children with epilepsy: A systematic review.

INTRODUCTION: Epileptic syndromes affecting children can sometimes be refractory to pharmacological treatments. Cannabinoids, especially cannabidiol, began to be studied to contribute to the treatment of these syndromes, configuring an expanding research area. The aim of this paper was to evaluate the scientific evidence available in the literature regarding the use of cannabinoids in the therapy of children with epilepsy. METHOD: This is a systematic literature review, carried out according to the structure of the Preferred Reporting Items for Systematic Reviews and meta-analyses (PRISMA), in the SCIELO, Cochrane Library, and MEDLINE databases. Observational studies or clinical trials were included, conducted in humans, addressing the use of cannabinoids in pediatric patients with epilepsy, published in the last 10 years. RESULTS AND DISCUSSION: In all, 626 studies were found and analyzed, of which 29 were considered eligible for the research; studies indicated good efficacy, safety, and tolerability of cannabidiol in several syndromes, with emphasis on Lennox-Gastaut and Dravet syndromes, in addition to practical issues were perceived regarding the applicability and expectations of patients and physicians. CONCLUSION: The use of cannabidiol was considered effective and safe, yet the studies were mostly carried out in the same countries.

Association between sleep pattern and pharmacological treatment in children with attention deficit disorder with hyperactivity: a systematic review.

OBJECTIVE: The aim of this study was to analyze the effect of the pharmacological treatment on the sleep patterns of children with attention deficit hyperactivity disorder (ADHD). DATA SOURCE: A high-sensitivity electronic search was performed in the following databases: Cochrane Library, MEDLINE via PubMed, LILACS via the Regional Health Portal (BVS), Embase, Scopus, CINAHL, and Web of Science, as recommended by the Cochrane Handbook, and which has undergone peer review according to the PRESS Guide. DATA SYNTHESIS: The studies contemplated the use of the drugs atomoxetine, guanfacine, methylphenidate, dasotraline, L-theanine, and lisdexamfetamine. They showed efficiency in reducing the symptoms of ADHD, although all, except atomoxetine, affected sleep quality, such as by reducing total rapid eye movement (REM), non-REM phase, slow-wave sleep time, and longer sleep-onset latency. CONCLUSIONS: The drugs used in the treatment of ADHD seem to have negative repercussions on the sleep quality of children, with the drug atomoxetine showing lesser effects on this variable.

Association between sleep pattern and pharmacological treatment in children with attention deficit disorder with hyperactivity: a systematic review / Associação entre padrão de sono e tratamento farmacológico em crianças com transtorno do déficit de atenção com hiperatividade: uma revisão sistemática

Abstract Objective: The aim of this study was to analyze the effect of the pharmacological treatment on the sleep patterns of children with attention deficit hyperactivity disorder (ADHD). Data source: A high-sensitivity electronic search was performed in the following databases: Cochrane Library, MEDLINE via PubMed, LILACS via the Regional Health Portal (BVS), Embase, Scopus, CINAHL, and Web of Science, as recommended by the Cochrane Handbook, and which has undergone peer review according to the PRESS Guide. Data synthesis: The studies contemplated the use of the drugs atomoxetine, guanfacine, methylphenidate, dasotraline, L-theanine, and lisdexamfetamine. They showed efficiency in reducing the symptoms of ADHD, although all, except atomoxetine, affected sleep quality, such as by reducing total rapid eye movement (REM), non-REM phase, slow-wave sleep time, and longer sleep-onset latency. Conclusions: The drugs used in the treatment of ADHD seem to have negative repercussions on the sleep quality of children, with the drug atomoxetine showing lesser effects on this variable.

RESUMO Objetivo: Analisar a interferência do tratamento farmacológico no padrão de sono das crianças com transtorno do déficit de atenção com hiperatividade (TDAH). Fontes de dados: Busca eletrônica de alta sensibilidade nas bases de dados Cochrane Library, Medical Literature Analysis and Retrieval System Online (MEDLINE) via United States National Library of Medicine (PubMed), Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS) via Biblioteca Virtual em Saúde (BVS), Embase, Scopus, Cumulative Index to Nursing and Allied Health Literature (CINAHL) e Web of Science, de acordo com o preconizado pelo Cochrane Handbook, de artigos que passaram pela revisão por pares segundo o Guia PRESS. Síntese dos dados: Os estudos que contemplaram o uso das drogas atomoxetina (ATX), guanfacina, metilfenidato (MPH), dasotralina, L-teanina e lisdexanfetamina mostraram eficiência na redução dos sintomas do TDAH, embora todos os medicamentos, exceto a atomoxetina, tenham afetado a qualidade do sono — reduzindo REM total, fase não REM, tempo de sono de ondas lentas e maior latência de início do sono. Conclusões: Os fármacos utilizados no tratamento do TDAH costumam cursar com repercussões negativas sobre a qualidade do sono de crianças, e o fármaco atomoxetina demonstrou menores efeitos sobre essa variável.

DNA Methylation-Based Prediction of Post-operative Atrial Fibrillation.

Background: Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and post-operative atrial fibrillation (POAF) is a major healthcare burden, contributing to an increased risk of stroke, kidney failure, heart attack and death. Genetic studies have identified associations with AF, but no molecular diagnostic exists to predict POAF based on pre-operative measurements. Such a tool would be of great value for perioperative planning to improve patient care and reduce healthcare costs. In this pilot study of epigenetic precision medicine in the perioperative period, we carried out bisulfite sequencing to measure DNA methylation status in blood collected from patients prior to cardiac surgery to identify biosignatures of POAF. Methods: We enrolled 221 patients undergoing cardiac surgery in this prospective observational study. DNA methylation measurements were obtained from blood samples drawn from awake patients prior to surgery. After controlling for clinical and methylation covariates, we analyzed DNA methylation loci in the discovery cohort of 110 patients for association with POAF. We also constructed predictive models for POAF using clinical and DNA methylation data. We subsequently performed targeted analyses of a separate cohort of 101 cardiac surgical patients to measure the methylation status solely of significant methylation loci in the discovery cohort. Results: A total of 47 patients in the discovery cohort (42.7%) and 43 patients in the validation cohort (42.6%) developed POAF. We identified 12 CpGs that were statistically significant in the discovery cohort after correcting for multiple hypothesis testing. Of these sites, 6 were amenable to targeted bisulfite sequencing and chr16:24640902 was statistically significant in the validation cohort. In addition, the methylation POAF prediction model had an AUC of 0.79 in the validation cohort. Conclusions: We have identified DNA methylation biomarkers that can predict future occurrence of POAF associated with cardiac surgery. This research demonstrates the use of precision medicine to develop models combining epigenomic and clinical data to predict disease.

"Climate change might have caused our small harvest": indigenous vulnerability, livelihoods, and environmental changes in lowland and high jungle indigenous communities in Peru.

The purpose of this article is to analyze how indigenous livelihoods are challenged by the global phenomenon of climate change while paying particular attention to how historically shaped, non-climatic factors influence how climate change is experienced in the Peruvian Amazon. In this sense, we will address indigenous people's lived experiences of climate variations using a theoretical framework based on concepts of vulnerability. Methodologically, we draw on both a recent literature review and fieldwork conducted during 2015 and 2016 with two Kukama Kukamiria communities in Loreto (low jungle) and three Ashaninka communities in Junín (high jungle). After describing our theoretical framework and qualitative methods, we discuss the economic history of the addressed areas and show how non-climatic factors, such as colonialism, influence these communities' experiences. This context allows us to better understand indigenous people's experience of seasonal variations, precipitations and climatic events, its effect on their livelihoods, and their adaptive strategies in response to challenges imposed by climate unpredictability and broader transformations in their territories. Our conclusions are twofold: (a) addressing climate change must incorporate multiple temporal and spatial scales and (b) non-climatic factors are integral to understanding the role of climate change vulnerability of indigenous population.

Analysis of agreement between peak expiratory flow meters and comparison of reference values / Análise da concordância entre aparelhos de pico de fluxo expiratório e comparação dos valores de referência

Abstract Introduction: The peak expiratory flow (PEF) is a practical method that evaluates the caliber of the proximal airways. The ease in handling and the low cost of portable PEF meters made their use frequent. However, few studies have examined the correlation between the different equipment and compared their reference values. Objective: Analyze the correlation of three portable meters of PEF and check if the reference values are applicable in the studied population. Methods: 168 healthy individuals, of both genders, ranging in age from 20 to 80 years, had their PEF measured in Mini-Wright®, Assess® and AirZone® and the values obtained were compared to those predicted by Leiner et al. (1963) and Nunn and Gregg (1989). Statistical analysis was performed by the Kolmogorov-Smirnov tests, ANOVA, Wilcoxon test, Spearman correlation and analysis of agreement of Bland-Altman (p< 0.05). Results: There was significant difference in the values of PEF obtained between the Mini-Wright® and Assess® meters in both genders, between the AirZone® and Assess® only in men and between the Mini-Wright® and AirZone® only in women. The predicted values in the three meters have overestimated the obtained in both genders; there was no correlation between the values obtained from three meters due to the great variation of agreement limits and large interindividual variation. Conclusion: The values obtained in the three meters are not interchangeable and the predicted values were unsuitable for the sample.

Resumo Introdução: O pico de fluxo expiratório (PFE) é um método acessível que avalia o calibre das vias aéreas proximais. A facilidade no manuseio e o baixo custo dos medidores portáteis de PFE tornaram seu uso frequente, entretanto, poucos estudos analisaram a concordância entre os diferentes equipamentos e compararam seus valores de referência. Objetivo: Analisar a concordância de três medidores portáteis de PFE e verificar se os valores de referência são aplicáveis na população estudada. Métodos: 168 indivíduos saudáveis, de ambos os gêneros, na faixa etária de 20 a 80 anos, realizaram medidas de PFE nos aparelhos Mini-Wright®, Assess® e AirZone® e comparou-se os valores obtidos aos previstos por Leiner et al. (1963) e Nunn e Gregg (1989). A análise estatística foi realizada pelos testes Kolmogorov-Smirnov, ANOVA, teste de Wilcoxon, correlação de Spearman e análise de concordância de Bland-Altman (p<0,05). Resultados: Constatou-se diferença significativa nos valores de PFE obt idos entre os medidores Mini-Wright® e Assess® em ambos os gêneros, entre o AirZone® e o Assess® apenas nos homens e entre o Mini-Wright® e o AirZone® somente nas mulheres, sendo que os valores previstos nos três aparelhos superestimaram os obtidos em ambos os gêneros; não se verificou concordância entre os valores obtidos dos três medidores devido à grande variação dos limites de concordância e grande variação interindividual. Conclusão: Os valores obtidos nos três medidores não são intercambiáveis e os valores previstos se mostraram inadequados para a amostra estudada.

Dinâmica microbiana em contrafilés bovinos embalados a vácuo: sistemas de terminação e tempo de estocagem / Microbial dynamics in the vacuum-packaged meat cuts: production system and storage period

A qualidade da carne embalada a vácuo é de grande importância para o comércio. Neste contexto, no presente estudo foi avaliada a dinâmica microbiana de cortes cárneos bovinos Longissimus dorsi, denominado comercialmente por contra filé, embalados a vácuo e armazenados a 0 ± 1 °C no estabelecimento de abate durante cinco períodos de estocagem. Foram analisadas amostras de cortes cárneos provenientes de bovinos anelorados, fêmeas, terminados em dois sistemas de produção, sendo 15 adultos criados a pasto, com média de 45 meses de vida e 15 bovinos jovens de 12 meses de idade em confinamento de alto desempenho. Procedeu-se a avaliação bacteriológica das carnes nos períodos de tempo correspondentes à zero, 30, 45, 60 e 75 dias após o abate e embalagem. A avaliação microbiológica foi efetuada pela contagem de aeróbios viáveis, bactérias ácido lácticas, Enterobacteriaceae, psicrotróficos, anaeróbios, determinaçãodo Número Mais Provável (NMP) de coliformes totais, coliformes termotolerantes e Escherichia coli, análise de pH e temperaturas dos cortes. O sistema de terminação influenciou parcialmente na dinâmica microbiana. As carnes embaladas a vácuo podem apresentar micro-organismos deteriorantes e patogênicos, provenientes de contaminação ambiental ou fecal. Quanto maior o período de estocagem dos cortes cárneos, a contagem de micro-organismos avaliados foi maior.

Photophysics and photochemical studies of the vitamin B6 group and related derivatives.

The photophysics and photochemical properties of vitamin B6 constituents and analogs were studied as function of pH and solvent. The pK of the phenolic oxygen and the pyridine ring nitrogen depends on the electron donor-acceptor ability of the 4-substituent, and agrees with the calculated proton affinity. For all studied compounds, the fluorescence properties showed that the phenolic oxygen is 8 units more acidic in the lowest singlet excited state than in the ground state. The pyridine N-atom is slightly more basic in the excited state. At pH of biological significance, pH 6-8, pyridoxamine and 4-pyridoxic acid are the more efficient chromophores with higher fluorescence yield and longer lifetime. Spectroscopic studies showed that the tautomeric equilibrium depends on the nature of the 4-substituent. The quenching of the singlet excited state of pyridoxamine and 4-pyridoxic acid by amino acids, free or in a peptide, and DNA bases at pH 7 was studied by time-resolved fluorescence techniques. The quenching rate constants are well correlated with the redox properties of the pyridoxinic compound and amino acids, and are related to the free energy change in the electron transfer process. Guanosine and pyrimidine bases also are efficient quenchers, involving an electron transfer reaction.

Photophysical properties of the prefluorescent nitroxide probes QT and C343T.

The photophysical properties of the nitroxide prefluorescent probes 4-(3-hydroxy-2-methyl-4-quinolinoyloxy)-2,2,6,6-tetramethyl-piperidin-4-yl) ester free radical (QT) and 2,3,4,6,7,8-hexahydro-quinolizino [1,10,9-gh] coumarin-3-carboxylic acid (1-oxyl-2,2,6,6-tetramethyl-piperidin-4-yl) ester free radical (C343T) were evaluated as a function of pH and solvent properties. The absorbance of QT showed high pH sensitivity. The pKa values for the different ionization forms involved in the acid-base equilibrium of the quinoline chromophore were determined in the ground and excited states. The fluorescence lifetimes of QT, and N-hydroxylamine (QTH) and quinoline methyl ester (QMe) derivatives, showed that the intramolecular quenching efficiency by the nitroxide moiety is independent of the quinoline ionization form. The fluorescence and absorbance of C343T were highly sensitive to solvent polarity in agreement with a charged transfer excited state of the chromophore. However, we noted a decrease in the intramolecular fluorescence quenching efficiency by the nitroxide moiety when changing the polarity of the solvent from hexane to water. This behavior has been attributed to a suppression of an energy transfer mechanism in the nitroxide quenching process in very polar solvents. The results obtained in micelles allow us to propose QT and C343T as sensors for pH and micropolarity, respectively, in addition to their role as monitors for free radicals or hydrogen transfer from phenols.

Simulação de pacientes: cursos de suporte de vida ACLS, BLS e PALS na FMRP-USP / Patient simulation: life support courses ACLS, BLS and PALS in the Medical school of Ribeirão Preto of the University of São Paulo

Os cursos de suporte de vida organizados e coordenados pela American Heart Association incluem as modalidades: Suporte Básico de Vida, Suporte Avançado de Vida em Cardiologia e Suporte de Vida Avançado em Pediatria. Esses cursos estão sendo disseminados mundialmente, especialmente após o estabelecimento de diretrizes internacionais estabelecendo consensos para o atendimento a emergências clínicas. O impacto da inserção destes cursos em instituições universitárias brasileiras ainda é desconhecido. O objetivo precípuo deste artigo é descrever a experiência de implantação de um centro de treinamento em Suporte de Vida no Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo (HCFMRP-USP), um hospital universitário público inserido no Sistema Único de Saúde. São discutidos aqui aspectos históricos, financiamento e gerenciamento, o impacto em atividades de pesquisa, ensino e de atenção à saúde tanto no contexto local, regional, nacional e internacional, bem como suas perspectivas futuras.

The American Heart Association Life Support courses, including Basic Life Support,Advanced Cardiac Life Support and Pediatric Advanced Life Support, are spreading across the world since the introduction of international guidelines for clinical emergencies. The impact of the insertion of these courses on university institutions is unknown. The goal of this article is to describe the experience to implement these courses at the University Hospital, Medical School ofRibeirão Preto, University of São Paulo (HCFMRP-USP), characterizing its historical evolution, impact on research, teaching and health care activities and also future perspectives.

Nucleotide specificity of Saccharomyces cerevisiae phosphoenolpyruvate carboxykinase Kinetics, fluorescence spectroscopy, and molecular simulation studies.

Phosphoenolpyruvate carboxykinases, depending on the enzyme origin, preferentially use adenine or guanine nucleotides as substrates. In this work, analyses of the substrate specificity of the Saccharomyces cerevisiae ATP-dependent enzyme have been carried out. Kinetics studies gave relative values of k(cat)/K(m) for the nucleoside triphosphate complexes in the order ATP>>GTP>ITP>UTP>CTP. For the nucleoside diphosphate complexes the order is ADP>>GDP>IDP congruent withUDP>CDP. This shows that the enzyme has a strong preference for ADP (or ATP) over other nucleotides, being this preference about an order of magnitude higher for the diphosphorylated than for the triphosphorylated nucleosides. The calculated binding free energies (kcalmol(-1)) at 25 degrees C are 7.39 and 6.51 for ATP and ADP, respectively. These values decrease with the nucleotide structure in the same order than the kinetic specificity. The binding energy for any triphosphorylated nucleoside is more favourable than for the corresponding diphosphorylated compound, showing the relevance of the P(gamma) for nucleotide binding. Homology models of the adenine and guanine nucleotides in complex with the enzyme show that the base adopts a similar conformation in the diphosphorylated nucleosides while in the triphosphorylated nucleosides the sugar-base torsion angle is 61 degrees for ATP and -53 degrees for GTP. Differences are also noted in the distance between P(beta) and Mn2+ at site 1. This distance is almost the same in the ATP, GTP, and UTP complexes, however in the ADP, GDP and UDP complexes it is 2.9, 5.1, and 7A, respectively. Experimental data obtained with a Thr463Ala mutant enzyme agree with molecular simulation predictions. The results here presented are discussed in terms of the proposed interactions of the nucleotides with the protein.

Substrate binding to fluorescent labeled wild type, Lys213Arg, and HIS233Gln Saccharomyces cerevisiae phosphoenolpyruvate carboxykinases.

Saccharomyces cerevisiae phosphoenolpyruvate (PEP) carboxykinase is a key enzyme of the gluconeogenic pathway and catalyzes the decarboxylation of oxaloacetate and transfer of the gamma-phosphoryl group of ATP to yield PEP, ADP, and CO(2) in the presence of a divalent metal ion. Previous experiments have shown that mutation of amino acid residues at metal site 1 decrease the steady-state affinity of the enzyme for PEP, suggesting interaction of PEP with the metal ion [Biochemistry 41 (2002) 12763]. To more completely understand this enzyme interactions with substrate ligands, we have prepared the phosphopyridoxyl (P-pyridoxyl)-derivatives of wild type, Lys213Arg, and His233Gln S. cerevisiae PEP carboxykinase and used the changes in the fluorescence probe to determine the dissociation equilibrium constants of PEP, ATPMn(2-), and ADPMn(1-) from the corresponding derivatized enzyme-Mn(2+) complexes. Homology modeling of P-pyridoxyl-PEP carboxykinase and P-pyridoxyl-PEP carboxykinase-substrate complexes agree with experimental evidence indicating that the P-pyridoxyl group does not interfere with substrate binding. ATPMn(2-) binding is 0.8kcalmol(-1) more favorable than ADPMn(1-) binding to wild type P-pyridoxyl-enzyme. The thermodynamic data obtained in this work indicate that PEP binding is 2.3kcalmol(-1) and 3.2kcalmol(-1) less favorable for the Lys213Arg and His233Gln mutant P-pyridoxyl-PEP carboxykinases than for the wild type P-pyridoxyl-enzyme, respectively. The possible relevance of N and O ligands for Mn(2+) in relation to PEP binding and catalysis is discussed.

Parada cardiorrespiratória (PCR) / Cardiac arrest

São revisados os princípios do atendimento da parada cardiorrespiratória, enfatizando a importância do suporte básico de vida e a conduta diferenciada na dependência dos três principais tipos de parada: fibrilação/taquicardia ventricular, assistolia e atividade elétrica sem puIso. Discutem-se os cuidados pós-reversão, a serem implementados, e sua importância na sobrevida

Vacinaçäo em hanseníase: tendências atuais / Present situation of vaccination in leprosy

Realizou-se revisäo bibliográfica sobre vacinaçäo em Hanseníase, procurando-se conhecer as tendências atuais das pesquisas realizadas nesta área. Verificou-se que essas podem ser divididas em dois grupos: aquelas que se limitam a buscar efeito imunoprofilático e aquelas que buscam também efeito imunoterapêutico, sendo que esta última vertente vem ganhando crédito. Dentre as vacinas em experimentaçäo, destacam-se: BCG, BCG associado ao M. leprae, ICRC e MW

Estudos de intervençäo sobre vacinaçäo BCG em hanseníase: uma análise comparativa / Trial studies about BCG vaccination against leprosy: a comparative analysis

De um total de 468 trabalhos publicados sobre BCG e Hanseníase, os autores selecionaram três trabalhos realizados em Uganda, Nova Guiné e Birmânia, para análise comaprativa. Foram estudados segundo populaçäo de referência; de estudo; critérios de participaçäo e locaçäo; programas oferecidos aos participantes e avaliaçäo. Encontrou-se uma eficácia que variou de 20 a 80 por cento. Diferenças metodológicas na escolha de populaçöes (referência/estudo) e/ou critérios (participaçäo/locaçäo/avaliaçäo) poderiam, entre outras causas, contribuir para explicar as diferentes eficácias encontradas