Search

Introdução: O uso de medicamentos possui várias vertentes. Por um lado,pode aumentar a expectativa de vida,tratamento de doenças; por outro lado, podem aumentar os custos da atenção à saúde se utilizados inadequadamente e/ou levar à ocorrência de reações adversas a medicamentos (RAM). As ações de farmacovigilância no âmbito hospitalar possibilitam a detecção precoce dos riscos associados a medicamentos e prevenção de RAM. Entretanto, vários estudos demonstram a subnotificação desses eventos, configurando um problema de saúde pública. OBJETIVO: Avaliar o impacto do número de notificações de suspeitas de RAM após implementação de ações educativas em um hospital sentinela. Métodos: Trata-se de um estudo observacional do tipo coorte, realizado em um hospital sentinela em Salvador – Bahiano período de outubro de 2018 a junho de 2019. Para avaliação do desfecho foram considerados informações advindas do banco de dados do serviço de farmacovigilância. Foram comparados o número de notificações mensais nos períodos pré e pós ações educativas que ocorreram no mês de abril. Para análise dos dados foi utilizado o programa Microsoft Office Excel 2016®. Resultados: Foram contabilizadas 418 notificações de reações adversas a medicamentos no período estudado. Destas 243 (58%) foram referentes ao período que antecedeu às ações educativas. Isso reflete uma média de 41 notificações/mês. Enquanto no período pós alcançou-se uma média de 59 notificações/mês. Outro achado significativo foi o aumento de notificações por parte da equipe assistencial. No primeiro período, a média mensal de notificações realizadas por enfermeiros foi igual a 10 e farmacêuticos igual a 12. Em contraste, no segundo período o número de notificações aumentou para ambos os grupos, sendo uma média mensal de 12 para enfermeiros e 20 para farmacêuticos. Conclusão: Mediante os resultados supracitados, foi notório o aumento no número de notificações de suspeitas de RAM. Esse resultado corrobora para a importância de medidas educativas como forma de sensibilização da equipe assistencial no que tange a percepção e consequente notificação de suspeitas de reações adversas no âmbito hospitalar. Sendo assim, essas ações devem ocorrer de forma contínua de modo a abranger todos os membros da equipe multidisciplinar, uma vez que o cuidado do paciente é compartilhado.

RESUMO Objetivou-se caracterizar a exposição humana à infecção por bactérias e vírus via ingestão, considerando os cenários: tratamento do lodo (cenário 1); uso do lodo como adubo agrícola (cenário 2) e consumo de hortaliças adubadas com lodo (cenário 3). A exposição foi caracterizada pelas concentrações de Escherichia coli, vírus entéricos cultiváveis (VEC) e colifagos somáticos (CS) nas amostras: lodo de esgoto em tratamento (LET), água de lavagem das mãos (ALM) no tratamento e no plantio, mistura solo + lodo (MSL) e hortaliças alface e cenoura. No cenário 1, em torno de 50-60 dias, as amostras LET apresentaram umidade < 10% e padrão classe A. Nas amostras LET, concentrações de CS variaram entre 9,1 × 102 e 1,9 × 105 UFP.g-1 ST e de VEC entre 2,42 e 7,15 UFP.g-1 ST. No cenário 2, CS foram detectados em 72% das amostras MSL com concentrações entre 10 e 330 UFP.mL-1. Concentrações de E. coli ≤ 102 NMP.100 mL-1 foram detectadas nas amostras ALM-tratamento (63,7%). Para vírus, todas as ALM-tratamento foram negativas e 17,4% das ALM-plantio apresentaram VEC entre 3 e 409,2 UFP.mL-1. Todas as amostras de alface foram negativas para CS e VEC. Considerando-se as características dos cenários avaliados, trabalhadores do serviço de saneamento, trabalhadores rurais e consumidores de hortaliças estiveram expostos a baixas concentrações de E. coli e VEC. CS foram resistentes ao tratamento térmico e ao plantio, o que sugere seu potencial como indicadores de VEC. ABSTRACT The aim of this study was to characterize human exposure to microbiological contamination (bacteria and viruses) via ingestion, considering the following scenarios: treatment of sludge (scenario 1); use of sludge as fertilizer (scenario 2) and consumption of vegetables fertilized with sludge (scenario 3). Exposure was characterized by the levels of Escherichia coli, cultivable enteric viruses (CEV) and somatic coliphages (SC) in the samples: sewage sludge under treatment (SST); handwashing water (HW) in treatment and planting; mix soil + sludge (MSL) and the vegetables lettuce and carrots. In scenario 1, SST samples presented < 10% humidity and class A pattern around 50-60 days; SC concentrations ranged from 9.1 × 102 to 1.9 × 105 PFU.g-1 TS, and CEV ranged from 2.42 to 7.15 PFU.g-1 TS. In scenario 2, CS were detected in 72% of HW samples, and concentrations ranged from 10 to 330 PFU.mL-1. E. coli concentrations ≤ 102 NMP.100 mL-1 were detected in HW-treatment samples (63.7%). Viruses were not detected in 100% of HW-treatments samples, and 17.4% of HW-plantings had CEV concentrations between 3 and 409.2 PFU.mL-1. All the vegetable samples were negative for SC and CEV. Considering the characteristics of the scenarios evaluated, sewage workers, rural workers and consumers of vegetables were exposed to low concentrations of E. coli and CEV. Somatic coliphages were resistant to heat treatment and planting, which supports their potential as indicators of CEV.

The articulation between different temporalities and spatialities is an important field of discussion for understanding historical information. When considering the Brazilian high school context, specifically the humanities curriculum, this paper discusses the use of a didactic tool for visualizing temporality to enhance the visual literacy of teachers and students as primary and secondary target groups, especially from a synchronic-diachronic perception of historical time. We investigate how the articulation of the multiplicities of time and space might mediate strategies for teaching and learning history, considering visual language in a currently changing curriculum for high school. To this end, we briefly describe the tool’s design in the previous phases of our research and its connection to curricular demands, data visualization, and traditional historiographical models. Through user evaluation, we discuss the reception of the tool among teachers and students, as well as the implications for cultural learning. The research was instigated by the distancing many students feel when attempting to place themselves within a historical narrative. During the learning experience, it is essential to understand how history is constructed by the participation of groups and individuals and not by distant, impersonal forces; this broadens the discipline of history to include the narratives of students’ lives. In addition, we understand that these social perceptions, which include those of time and space, are lived through multiple languages and cognition channels and are mediated by the teachers. Thus, visual language acts as a mediating device for teaching and learning information literacy so that all narratives can be more easily addressed and all learners are perceived as active agents of social change.

Resumo Introdução Durante as três décadas do Sistema Único de Saúde (SUS), a tríade universalidade/integralidade/igualdade esteve complementada pela garantia de acesso, que, apesar de importantes avanços, também registrou a manutenção de desafios e, até, retrocessos. Objetivo Compreender os aspectos imbricados com o acesso à rede de atenção à saúde. Método Entrevistas e grupos focais foram realizados com 32 profissionais de saúde, incluindo gestores, de um município da Região Metropolitana de Belo Horizonte caracterizado por marcada vulnerabilidade social e econômica. As dimensões teóricas “estrutural”, “operacional” e “relacional” guiaram a análise e interpretação da narrativa dos profissionais. Resultados Os resultados demonstraram que a dimensão estrutural assumiu centralidade na narrativa dos profissionais de saúde como determinantes para o acesso, relacionada não apenas ao financiamento, mas também a questões afetas à operacionalização e organização dos serviços de saúde, como rotatividade dos profissionais e planejamento territorial. Conclusão Muitas dessas questões não são passíveis de intervenções, pelo menos de forma direta e em curto prazo pelos profissionais de saúde, incluindo gestores. No entanto, reconhecer e refletir sobre sua influência no acesso aos serviços da rede de saúde municipal pode ser um produtivo caminho no sentido de articulação, proposição e implementação de estratégias. Abstract Background During the three decades of the Unified Health System (SUS), the triad of universality/integrality/equality was complemented by the guarantee of access, which despite important advances, also registered the maintenance of challenges and even setbacks. Objective To understand the factors that influenced access to public health services. Method Interviews and focus groups were realized with 32 health professionals including managers from a municipality in the metropolitan region of Belo Horizonte characterized by the marked social and economic vulnerability. The theoretical structural, operational, and relational dimensions guided the analysis and interpretation of the professionals' narrative. Results The results showed that the structural dimension assumed a central role in the narrative of health professionals as determinants of access related not only to financing but also to questions related to the operability and organization of health services such as professional rotation and territorial planning. Conclusion Many of these issues are not amenable to interventions at least directly and in short terms by health professionals including managers, however, recognizing and reflecting on their influence on access to municipal health network services can be a productive path towards articulation, proposition, and implementation’s strategies.

The buffalo herds in Brazil have been an alternative for increasing the economy in different biomes. For this reason, knowledge of the spatial distribution of diseases of mandatory notification in buffalo herds, such as brucellosis and tuberculosis, is essential to guarantee the quality of exported animal products, as well as assist in strategies of national control and eradication programs. In the present study, we aimed to evaluate the spatiotemporal distribution and temporal trends of brucellosis and tuberculosis in buffalo in Brazilian states between 2012-2019. During this period, 474 cases of brucellosis and 604 cases of tuberculosis were observed in buffalo in Brazil, with no significant differences between the total number of cases and incidence risk. The spatial distribution for the states was mostly heterogeneous, showing similarities of occurrences for both diseases in the south, north, and the states of Minas Gerais and Pernambuco. In the eight years evaluated, tuberculosis showed cyclical variation every 1-2 years; however, for brucellosis, there was a cyclical trend only between 2012-2015, with a significant decrease until 2018. Among Brazilian states, Para had greater disease case numbers, with 34 % for brucellosis and 40.6 % for tuberculosis. Temporal trend analysis showed an increase for Pernambuco (annual percentage change [APC]: 21.0 [CI = 20.3; 21.8]), Parana (APC: 27.1 [CI = 5.6; 53.0]), and Santa Catarina (APC: 10.4 [CI = 0.8; 21.0]) for brucellosis, and for tuberculosis, only for Santa Catarina state (APC: 24.1 [CI = 15.5; 33.3]). Spatiotemporally, there were four high-risk brucellosis clusters with a primary cluster, cluster A (relative risk [RRs] = 53.42, P < 0.001), involving the state of Amazonas between 2014-2015. For tuberculosis, there were three states of high risk, with a primary cluster, cluster E (RRs = 28.18, P < 0.001), involving the states of Para, Roraima, Amazonas, Rondonia, and Acre in 2014. In conclusion, brucellosis and tuberculosis in buffalo in Brazil are heterogeneously distributed, with well-defined regions of high historical risk of infection. Among these regions, the states of Amazonas, Para, Amapa, and Minas Gerais stand out due to the higher risk of infection for both brucellosis and tuberculosis, alerting Brazilian authorities to the need for disease control actions.

Current studies estimate that 1-3% of females with unexplained Intellectual Disability (ID) present de novo splice site, nonsense, frameshift, or missense mutations in the DDX3X protein (DEAD-Box Helicase 3 X-Linked). However, the cellular and molecular mechanisms by which DDX3X mutations impair brain development are not fully comprehended. Here, we show that the ID-linked missense mutation L556S renders DDX3X prone to aggregation. By using a combination of biophysical assays, in vitro and in vivo imaging approaches, we demonstrate that this mutant assemble solid-like condensates and amyloid-like fibrils. Although we observed greatly reduced expression of the mutant allele in the patient who exhibits skewed X inactivation, this appears to be enough to sequestrate healthy protein into solid-like ectopic granules, compromising cell function. Reduced viability of SH-SY5Y cells and impaired development of patient-derived brain organoids unfold with aberrant granules formation. Therefore, our data suggests ID-linked DDX3X L556S mutation as a disorder arising from protein misfolding and aggregation.

Mebendazole is an anthelmintic drug of low solubility, which exhibits three polymorphic forms (A, B, and C) with different thermodynamic stability (A > C > B). Form C is the most appropriate for pharmaceutical development due to its adequate bioavailability and lower toxicity. This form is stable between room temperature ± 180 °C. The aim of this work was to characterize and study the thermal degradation kinetics of Mebendazole polymorphs A and C by isothermal and non-isothermal (Ozawa method) thermogravimetric methods. Thermogravimetry (TG), differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD), Fourier-transform infrared spectroscopy (FTIR), and elementary analysis (EA) were used to identify Mebendazole polymorphs A and C. Isothermal and non-isothermal thermogravimetric methods were used to study the thermal degradation kinetics of Mebendazole polymorphs. The results showed that form C converts to the polymorphic form A after heating at 200 °C, exhibiting both exothermic and endothermic events before the first mass loss. Subsequent to this transformation, CO2 was released and the formation of a solid product occurred, which was characterized by EA and FTIR. These results suggested the presence of a Mebendazole impurity. The degradation kinetics studies of polymorphs A and C obtained by both methods indicated activation energy (Ea) values greater for polymorph C. In fact, part of the energy provided to the polymorph C was used for the transformation to polymorph A, which explains its greater thermal stability. This indicates that polymorph C is very stable under ambient conditions, but at high temperatures (above 180 °C) the stability of polymorph A predominates.

Agradecimentos: LNBio/CNPEM; Brazilian National Council for Scientific and Technological Development (CNPq)National Council for Scientific and Technological Development (CNPq) [306879/2014-0, 310536/2014-6, 422790/2016-8]; Sao Paulo Research Foundation (FAPESP)Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [2012/50981-5, 2013/08028-1, 2015/06281-7]; NIH/NIGMSUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of General Medical Sciences (NIGMS) [R01 GM088055] Ubiquitin-conjugating enzymes (E2) enable protein ubiquitination by conjugating ubiquitin to their catalytic cysteine for subsequent transfer to a target lysine side chain. Deprotonation of the incoming lysine enables its nucleophilicity, but determinants of lysine activation remain poorly understood. We report a novel pathogenic mutation in the E2 UBE2A, identified in two brothers with mild intellectual disability. The pathogenic Q93E mutation yields UBE2A with impaired aminolysis activity but no loss of the ability to be conjugated with ubiquitin. Importantly, the low intrinsic reactivity of UBE2A Q93E was not overcome by a cognate ubiquitin E3 ligase, RAD18, with the UBE2A target PCNA. However, UBE2A Q93E was reactive at high pH or with a lowpK a amine as the nucleophile, thus providing the first evidence of reversion of a defective UBE2A mutation. We propose that Q93E substitution perturbs the UBE2A catalytic microenvironment essential for lysine deprotonation during ubiquitin transfer, thus generating an enzyme that is disabled but not dead FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQ Fechado

The sediments are solid materials deposited at the bottom of water bodies. The toxic heavy metals tend to be deposited as sediments, so they are monitored after being dredged to ensure their correct disposal. As there are no Brazilian reference materials for sediments, chemical-analysis laboratories use imported materials to control the quality of their measurements. In this work, a pilot batch of material was prepared from a sediment collected in the Upper Estuary of Santos (SP). The chemical characterization of the material was performed by ICP-OES and ICP-MS, using alkaline fusion or microwave digestion to sample dissolution according to the element to be analyzed. A material with a narrow particle size distribution and suitable homogeneity was obtained. The applied methodologies and the preparation process developed are suitable for the preparation of a future certified reference material. Keywords: sediment; reference material; ICP-OES; ICP-MS.

RESUMO O presente trabalho objetivou avaliar o processo de secagem térmica de lodos de esgoto em estufa agrícola com vistas à inativação bacteriana e de vírus, além do comportamento de colifagos somáticos como indicadores desses organismos. Cada volume de lodo de esgoto excedente descartado de reator upflow anaerobic sludge blanket (UASB) foi desaguado em leito de secagem por 14 dias e direcionado para secagem em estufa agrícola correspondeu a um lote (L) de lodo. Entre fevereiro e novembro de 2015, foram tratados 9 lotes (L1 a L9) por, em média, 13 semanas. O pH se manteve estável na maioria deles (entre 5,0-6,0). Após, aproximadamente, 60 dias de tratamento, todos os lotes apresentavam umidade abaixo de 10%, exceto L3 e L4 (10-25%). O tempo necessário para atingir 90% de sólidos totais (ST) variou entre 40-50 (L1 e L7), 60 (L5 e L6) e 85-100 (L2, L3 e L4) dias. Os lotes levaram, em média, 50-60 dias para alcançarem níveis de E. coli iguais ou menores a 1x103 número mais provável (NMP)/g de ST. A detecção de colifagos somáticos foi baixa e eventual. O ensaio de inoculação mostrou decaimento rápido de vírus (Poliovírus 1 Sabin), mas colifago somático Phi X174 mostrou-se mais persistente nas três temperaturas avaliadas (estufa agrícola, controladas em laboratório - 30 e 60°C). O tratamento térmico de lodo de esgoto em estufa agrícola se apresentou como simples e eficiente na obtenção de produto granulado, seco e com níveis de redução da contaminação bacteriana atendendo ao parâmetro estabelecido como seguro para uso agrícola conforme a legislação brasileira. ABSTRACT The aim of the study was to evaluate the thermic drying of sewage sludge in agricultural greenhouse, in order to inactivate bacterial and virus, and to evaluate the behavior of somatic coliphages as indicator of these organisms. Each volume of excess sewage sludge discarded from UASB reactor, drained in a drying bed for 14 days and directed to thermic drying treatment in greenhouse corresponded to a batch (B) of sludge. Between February and November 2015, nine batches (L1 to L9) were treated for an average of 13 weeks. Most batches kept the pH between 5.0-6.0. After about 60 days of treatment, all batches showed humidity below 10%, except B3 and B4 (10-25%). The time required to reach 90% of total solids ranged between 40-50 (B1 to B7), 60 (B5, B6) and 85-100 (B2, B3 and B4) days. On average, levels of E. coli reduced to

Phosphate-activated glutaminases catalyze the deamidation of glutamine to glutamate and play key roles in several physiological and pathological processes. In humans, GLS encodes two multidomain splicing isoforms: KGA and GAC. In both isoforms, the canonical glutaminase domain is flanked by an N-terminal region that is folded into an EF-hand-like four-helix bundle. However, the splicing event replaces a well-structured three-repeat ankyrin domain in KGA with a shorter, unordered C-terminal stretch in GAC. The multidomain architecture, which contains putative protein-protein binding motifs, has led to speculation that glutaminases are involved in cellular processes other than glutamine metabolism; in fact, some proteins have been identified as binding partners of KGA and the isoforms of its paralogue gene, GLS2. Here, a yeast two-hybrid assay identified nuclear receptor peroxisome proliferator-activated receptor γ (PPARγ) as a new binding partner of the glutaminase. We show that KGA and GAC directly bind PPARγ with a low-micromolar dissociation constant; the interaction involves the N-terminal and catalytic domains of glutaminases as well as the ligand-binding domain of the nuclear receptor. The interaction occurs within the nucleus, and by sequestering PPARγ from its responsive element DR1, the glutaminases decreased nuclear receptor activity as assessed by a luciferase reporter assay. Altogether, our findings reveal an unexpected glutaminase-binding partner and, for the first time, directly link mitochondrial glutaminases to an unanticipated role in gene regulation.

Altered energy metabolism is a cancer hallmark as malignant cells tailor their metabolic pathways to meet their energy requirements. Glucose and glutamine are the major nutrients that fuel cellular metabolism, and the pathways utilizing these nutrients are often altered in cancer. Here, we show that the long ncRNA CCAT2, located at the 8q24 amplicon on cancer risk-associated rs6983267 SNP, regulates cancer metabolism in vitro and in vivo in an allele-specific manner by binding the Cleavage Factor I (CFIm) complex with distinct affinities for the two subunits (CFIm25 and CFIm68). The CCAT2 interaction with the CFIm complex fine-tunes the alternative splicing of Glutaminase (GLS) by selecting the poly(A) site in intron 14 of the precursor mRNA. These findings uncover a complex, allele-specific regulatory mechanism of cancer metabolism orchestrated by the two alleles of a long ncRNA., G.A.C. is The Alan M. Gewirtz Leukemia & Lymphoma Society Scholar. Work in G.A.C.’s laboratory is supported in part by the NIH/NCI grants 1UH2TR00943-01 and 1 R01 CA182905-01, the UT MD Anderson Cancer Center SPORE in Melanoma grant from NCI (P50 CA093459), Aim at Melanoma Foundation and the Miriam and Jim Mulva research funds, the Brain SPORE (2P50CA127001), the Center for Radiation Oncology Research Project, the Center for Cancer Epigenetics Pilot project, a 2014 Knowledge GAP MDACC grant, a CLL Moonshot pilot project, the UT MD Anderson Cancer Center Duncan Family Institute for Cancer Prevention and Risk Assessment, a SINF grant in colon cancer, the Laura and John Arnold Foundation, the RGK Foundation, and the Estate of C.G. Johnson, Jr. I.B.-N. was financed by a grant entitled Non-Invasive Intelligent Systems for Colorectal Cancer Diagnosis and Prognosis Based on circulating miRNAs Integrated in the Clinical Workflow – INTELCOR. S.M.G.D., A.L.B.A., and D.A. are supported by the São Paulo Research Foundation FAPESP under grants 2014/15968-3, 2014/20673-2, and 2014/17820-3, respectively. W.L. was partly supported by grants from The University of Texas MD Anderson Cancer Center Sheikh Ahmed Bin Zayed Al Nahyan Center for Pancreatic Cancer Research. J.A.B. was supported by the Cancer Center Support Grant (P30 CA016672), and the HP imaging program of the Small Animal Facility (SAIF) was supported by the Cancer Prevention and Research Institutes of Texas grant RP-101243P5. H.L. was supported by NIH/NCI grant R01CA175486, a grant (RP140462) from the Cancer Prevention and Research Institute of Texas, and the R. Lee Clark Fellow Award from The Jeanne F. Shelby Scholarship Fund. I.B.-N. was financed by a Fulbright fellowship and by a grant entitled Non-Invasive Intelligent Systems for Colorectal Cancer Diagnosis and Prognosis Based on circulating miRNAs Integrated in the Clinical Workflow – INTELCOR.

The purpose of this study was to evaluate the physicochemical properties and kinetic analyses of membranes obtained through the dispersion of pectin PEC (2 %), with or without the extract of Morinda citrifolia Linn EMC2.5 and 5.0 % in distilled water, and adding plasticizer propylene glycol (20 %). The thickness of the membranes was significantly different, and at SEM images of PEC2.5 %, they showed a more compact structure compared with other membranes. PEC5.0 % membrane showed the best values of mechanical properties. The DSC curve of EMC showed two endothermic events, and the DSC curves of the membranes presented two endothermic events and two exothermic events with profiles similar to PEC, PEC2.5 and PEC5.0 % membranes. A kinetic study was performed with thermogravimetry using the Ozawa method and non-Arrhenius methods. The kinetic parameters showed that the PEC and PEC5.0 % present a similar thermal stability. Thus, the Morinda citrifolia extract influences a more organized membrane structure, and the PEC-EMC2.5 % has the best characteristics for the development of a membrane with healing effect.

Ambuphylline is a drug obtained by the combination of theophylline and 2-amino-2-methyl-1-propanol. Thermal decomposition of ambuphylline was studied using thermogravimetry and differential scanning calorimetry. Under thermal decomposition, ambuphylline exhibits two degradation steps that are clearly separated. In this paper, the kinetic analysis of the first decomposition step has been carried out by employing the incremental isoconversional method for kinetic analysis based on the orthogonal distance regression. The kinetic parameters of the Arrhenius and Berthelot–Hood temperature functions were evaluated. The results obtained show that the ambuphylline degradation exhibits an induction period for temperatures close to the ambient one. After finishing the induction period, the decomposition proceeds rapidly.

The formation of inclusion complexes of Hyptis pectinata essential oil (EOHP), with potent activities such as anti-nociceptive, anti-inflammatory, among others, with β -cyclodextrin (β-CD), was obtained by slurry (SC) and paste procedures (PC). The gas chromatography coupled to the mass spectrometry (GC/MS) analysis demonstrated a total of 36.4% monoterpenes and 63.6% sesquiterpenes in the EOHP. The major components of EOHP were identified as (E)- caryophyllene (54.07%). The analysis of samples (PM, PC and SC) by GC/MS involved the surface and the total extracted oils. The GC/MS results suggested important differences between in SC and PC methods indicating the complexation of mono and sesquiterpenoids in different ratios. Furthermore, the thermal analysis techniques suggests the complexation, especially in SC, which show a thermogravimetry/derivative thermogravimetry (TG/DTG) peak at 140-270oC, probably related to oil loss. Scanning electron microscopy (SEM) images showed reduction size of the samples mainly in the SC product. Additionally, EOHP/ β-CD improves pharmacological profile of EOHP alone in formalin-induced pain protocol in mice.

Para que as informações contábeis sejam úteis às partes interessadas é necessário, entre outros aspectos, que elas sejam relevantes na revelação do desempenho organizacional. Os estudos sobre a relevância da informação contábil buscam analisar, de maneira geral, se as variações nos preços/retornos das ações guardam relação com as informações contábeis. Ou seja, verificam a relevância das informações contábeis sob a ótica dos investidores (mercado de capitais). Nesse sentido, neste trabalho buscou-se analisar se as informações contábeis são capazes de explicar as variações ocorridas no preço da ação das empresas listadas na Bolsa de Valores de São Paulo (BM&FBovespa), utilizando o Lucro Líquido (LL), o Lucro Abrangente (LA) e o Fluxo de Caixa Operacional (FCO). A partir da base de dados Economática®, foram coletadas as informações referentes ao LL, ao FCO e a Outros Resultados Abrangentes (ORAs) de 2010 a 2013. Os resultados revelam que, de maneira geral, para o mercado brasileiro de capitais, o LL se mostrou mais relevante. Em seguida, observou-se que o LA foi o mais relevante. Por outro lado, constatou-se que o FCO apresentou menor relevância; isso pode estar associado ao fato de que o lucro atende a diversas demandas, o que pode justificar maior interesse dos usuários (investidores) por essa medida de desempenho em comparação com as demais informações analisadas.Palavras-chave: Relevância da informação contábil. Lucro Líquido. Fluxo de Caixa Operacional. Lucro Abrangente. Abstract For the accounting information to be useful to stakeholders, it is required, among other things, that they are relevant in the development of organizational performance. Studies on value relevance seek to analyze, in general, if the changes in prices/stock returns are related to the accounting information. So, they check the value relevance from the perspective of investors (capital markets). In this sense, this study sought to examine if the accounting information is able to explain the variations in the share price of companies listed on the São Paulo Stock Exchange (BM&FBovespa), using Net Income (NI), Comprehensive Income (CI) and Operating Cash Flow (OCF). The information for the NI, OCF and Other Comprehensive Income (OCI) of the years 2010 to 2013 were collected from the Economática® database. The results show that, in general, for the Brazilian capital market, the NI proved to be more relevant. Then it was observed that CI is the most relevant. Moreover, it was found that the OCF showed less relevance; this may be associated with the fact that profit meets various demands, what could justify greater interest of users (investors) by that measure performance in comparison to other information analyzed.Keywords: Value relevance. Net Profit. Operating Cash Flow. Comprehensive Income.

(−)-Linalool is a monoterpene alcohol which is present in the essential oils of several aromatic plants. Recent studies suggest that (−)-linalool has antimicrobial, anti-inflammatory, anticancer, antioxidant, and antinociceptive properties in different animal models. The aim of this study was to prepare and characterize inclusion complexes of (−)-linalool with β-cyclodextrin (β-CD). Equimolar binary (−)-linalool/β-CD systems were prepared by physical mixture, paste (PM), and slurry methods (SC) and characterized by differential scanning calorimetry, thermogravimetric analysis, FT-IR spectroscopy, X-ray diffractometry, Karl Fisher titration, and scanning electron microscopy. Thermal characterization indicates the occurrence of complexation, mainly in paste complexes, which is present in the interval from 140 to 280 °C a gradual mass loss (4.6 %), probably related to (−)-linalool loss. FT-IR spectra showed changes that may be related to the formation of intermolecular hydrogen bonds between (−)-linalool and β-CD. The new solid-phase formed using the PM and SC methods, had a crystal structure which was different from the original morphology of β-CD.

Sendo o saneamento básico um serviço de infraestrutura fundamental na promoção da saúde pública em uma localidade, este trabalho foi realizado com o objetivo de relacionar os impactos na saúde da população e os custos gerados, devido à ineficiência do serviço de saneamento ambiental no Brasil. Destacam-se para a elaboração desse estudo duas etapas: 1) análise do número de casos, por região geográfica, de 10 dentre as principais doenças de veiculação hídrica no período de 2001 a 2010; e 2) comparação entre o número de casos das mesmas doenças com as informações de gastos/investimentos em saúde e saneamento e crescimento populacional no mesmo período. Pode-se verificar que o número de casos ao longo dos anos não sofreu retrocesso significativo, como seria de se esperar. Isso pode ser justificado pela falta de investimentos adequados em saneamento gerando, portanto, uma má prestação dos serviços de coleta e tratamento de esgoto sanitário, de gestão de resíduos sólidos urbanos, de manejo de águas pluviais urbanas e de abastecimento público de água. A ineficiência destes serviços implica diretamente no aumento dos gastos com a saúde pública para tratar os sintomas das doenças de veiculação hídrica, gerando um modelo de gestão insatisfatório. Assim, o estudo afirma a importância do saneamento, como forma preventiva e eficaz, na melhoria dos índices de saúde pública no Brasil.

Hypoxia-inducible transcription factors (HIF) form heterodimeric complexes that mediate cell responses to hypoxia. The oxygen-dependent stability and activity of the HIF-α subunits is traditionally associated to post-translational modifications such as hydroxylation, acetylation, ubiquitination and phosphorylation. Here we report novel evidence showing that unsaturated fatty acids are naturally occurring, non-covalent structural ligands of HIF-3α, thus providing the initial framework for exploring its exceptional role as a lipid sensor under hypoxia.

O presente trabalho propõe o uso das cinzas de dois resíduos agroindustriais - casca de arroz e bagaço de cana-de-açúcar - como fonte de sílica (SiO2) para a síntese de sílicas mesoporosas altamente ordenadas. Esta aplicação, além de agregar valor aos resíduos, busca uma alternativa ao tetraetil ortossicato, uma fonte de sílica dispendiosa, cuja obtenção resulta em danos ambientais. Amostras de cascas arroz de quatro procedências distintas foram caracterizadas por termogravimetria/ termogravimetria derivada (TG/DTG), calorimetria exploratória diferencial (DSC) e análise elementar de CHN. Com base nestes resultados, duas amostras foram selecionadas para obtenção de sílica. Outras duas amostras de bagaço de cana-de-açúcar de origens diferentes foram também caracterizadas por esta metodologia. Para melhor entender as etapas de degradação térmica da matéria orgânica, os resultados de TG/DTG foram associados aos de FT-IR e um estudo cinético por TG foi realizado. Diferentes tratamentos em meio ácido, com o objetivo de remover impurezas e reduzir o tempo necessário para calcinação dos materiais, foram realizados. O método escolhido para cada um dos materiais foi definido a partir dos testes e por avaliação de resultados de TG/DTG. As cinzas obtidas após calcinação em mufla dos materiais com e sem tratamento ácido prévio, foram caracterizadas por MEV/EDS, DRX e isotermas de adsorção/dessorção de N2. As cinzas das amostras com tratamento apresentaram maior pureza que as não tratadas e, para as obtidas a partir casca de arroz, foram amorfas e com alta área superficial BET (200-300 m2.g-1). A síntese de sílicas mesoporosas foi testada empregando-se as cinzas isoladas de amostras tratadas em meio ácido utilizando três rotas sintéticas diferentes. Em uma delas foi possível obter um material de morfologia esférica, com área superficial BET de cerca de 500 m2.g-1 e diâmetro de poro médio (BJH) de 4 nm. A caracterização por espalhamento de raios X a baixo ângulo (SAXS) revelou um ordenamento hexagonal dos poros. Um material de mesma morfologia foi obtido empregando-se silicato de sódio comercial ao invés das cinzas. Os materiais obtidos possuem potencial para diversas aplicações, destacando-se o uso no empacotamento de colunas para cromatografia líquida, encapsulação de fármacos com liberação controlada, catálise e suporte para deposição de materiais. This work proposes the use of ashes of two agro-industrial wastes - rice husk and sugar cane bagasse - as a source of silica (SiO2) for the synthesis of highly ordered mesoporous silicas. This application, besides adding value to waste, aims an alternative to ortossicato tetraethyl, an expensive source of silica, whose obtaining causes environmental damage. Samples of rice husks from four different sources were characterized by thermogravimetry / derivative thermogravimetry (TG / DTG), differential scanning calorimetry (DSC) and elemental CHN analysis. Based on these results, two samples were selected to obtain silica. Two other samples of sugar cane bagasse from different sources were also characterized by this methodology. To better understand the steps of thermal degradation of organic matter, the results of TG / DTG were associated with FT-IR and a kinetic study was performed by TG. Different treatments in an acid medium were carried out with the aim of removing impurities and reduce the time required for calcination of the materials. The method chosen for each material was defined from the tests and from evaluation of the results of TG / DTG. The ash obtained after the calcination of materials in muffle furnace, with and without prior acid treatment, were characterized by SEM / EDS, XRD and isotherms of adsorption/desorption of N2. The treated samples ashes showed higher purity than those not treated, and for those obtained from rice hulls were amorphous and with high BET surface area (200-300 m2.g-1). The synthesis of mesoporous silicas were tested employing the isolated ash samples treated in acid medium using three different synthetic routes. In one of them it was possible to obtain a spherical morphology material with BET surface area of 500 m2.g-1 and average pore diameter (BJH) of 4 nm. The characterization by small angle X-ray scattering (SAXS) showed a hexagonal ordering of the pores. A material with the same morphology was obtained employing commercial sodium silicate instead of the ash. The synthetized materials have potential for many applications, including packaging of liquid chromatography columns, encapsulation of drugs with controlled release, catalysis and support for deposition of materials.

A amplitude das atribuições da vigilância da qualidade da água para consumo humano (VQACH) associada à heterogeneidade dos municípios brasileiros (perfil demográfico e epidemiológico, recursos humanos e financeiros) impõe ao nível local de gestão o desafio de implementar com efetividade e sustentabilidade as ações previstas no modelo de atuação da VQACH. Tendo como cenário de estudo um município mineiro de pequeno porte, o trabalho apresenta desafios e possibilidades vivenciados durante a implementação do modelo. O atendimento às ações estratégicas e básicas e aos princípios doutrinários, organizacionais e executivos previstos no modelo de atuação foi verificado e as estratégias para o enfrentamento dos desafios impostos ao exercício da VQACH foram apresentadas. A conformação de uma equipe de profissionais em quantidade e qualidade compatíveis com as ações de VQACH foi aspecto fundamental, além da melhor explicitação de procedimentos como análise integrada dos sistemas de informação e análise e classificação do grau de risco à saúde das diferentes formas de abastecimento de água. O estudo permite adiantar aos gestores dos diferentes níveis de governo desafios e estratégias para contorná-los, bem como instrumentaliza a coordenação da VQACH no nível federal sobre questões que necessitam tratamento mais detalhado e específico. The magnitude of drinking-water quality surveillance (DWQS) attributions in meeting its primary function of health protection, associated with the heterogeneity of Brazilian municipalities (demographic and epidemiological profile, human and financial resources), is an important challenge in implementing actions which are effective and sustainable at the local level. The study presents the experience in rolling out the national operation model for DWQS in a small municipality in Minas Gerais state. The paper whether the strategic and basic actions and the doctrinal, organizational and executive principles provided in the operation model were achieved and how they were accomplished. Also, certain strategies for confronting the challenges imposed by DWQS assignment were presented. The existence of a well prepared and measured professional team is a fundamental aspect in achieving the DWQS objectives. In addition, some procedures should have clear guidelines, such as the integrated analysis of information systems and analysis and health risk classification of water supplies. In conclusion, different challenges must be overcome to implement drinking-water quality surveillance at the local level and managers could experience some difficulties. Federal level managers should be aware of issues that require more detailed and specific treatment.

The phosphate-dependent transition between enzymatically inert dimers into catalytically capable tetramers has long been the accepted mechanism for the glutaminase activation. Here, we demonstrate that activated glutaminase C (GAC) self-assembles into a helical, fiber-like double-stranded oligomer and propose a molecular model consisting of seven tetramer copies per turn per strand interacting via the N-terminal domains. The loop 321LRFNKL326 is projected as the major regulating element for self-assembly and enzyme activation. Furthermore, the previously identified in vivo lysine acetylation (Lys311 in humans, Lys316 in mouse) is here proposed as an important down-regulator of superoligomer assembly and protein activation. Bis-2-(5-phenylacetamido-1,3,4-thiadiazol-2-yl)ethyl sulfide, a known glutaminase inhibitor, completely disrupted the higher order oligomer, explaining its allosteric mechanism of inhibition via tetramer stabilization. A direct correlation between the tendency to self-assemble and the activity levels of the three mammalian glutaminase isozymes was established, with GAC being the most active enzyme while forming the longest structures. Lastly, the ectopic expression of a fiber-prone superactive GAC mutant in MDA-MB 231 cancer cells provided considerable proliferative advantages to transformed cells. These findings yield unique implications for the development of GAC-oriented therapeutics targeting tumor metabolism. Background: GAC supplies for increased metabolic needs of tumors because of exclusive localization and kinetic properties. Results: Higher than tetramer oligomers are the active form in in vitro and in cellular assays. Bis-2-(5-phenylacetamido-1,3,4-thiadiazol-2-yl)ethyl sulfide disrupts oligomers. Conclusion: A novel molecular mechanism for GAC activation is proposed. Significance: The data affect the development of therapies targeting GAC in tumors, with emphasis on allosteric inhibitors.

The necrosis- and ethylene-inducing peptide 1 (NEP1)-like proteins (NLPs) are proteins secreted from bacteria, fungi and oomycetes, triggering immune responses and cell death in dicotyledonous plants. Genomic-scale studies of Moniliophthora perniciosa, the fungus that causes the Witches' Broom disease in cacao, which is a serious economic concern for South and Central American crops, have identified five members of this family (termed MpNEP1-5). Here, we show by RNA-seq that MpNEP2 is virtually the only NLP expressed during the fungus infection. The quantitative real-time polymerase chain reaction results revealed that MpNEP2 has an expression pattern that positively correlates with the necrotic symptoms, with MpNEP2 reaching its highest level of expression at the advanced necrotic stage. To improve our understanding of MpNEP2's molecular mechanism of action, we determined the crystallographic structure of MpNEP2 at 1.8 Å resolution, unveiling some key structural features. The implications of a cation coordination found in the crystal structure were explored, and we show that MpNEP2, in contrast to another previously described member of the NLP family, NLP(Pya) from Pythium aphanidermatum, does not depend on an ion to accomplish its necrosis- and electrolyte leakage-promoting activities. Results of site-directed mutagenesis experiments confirmed the importance of a negatively charged cavity and an unforeseen hydrophobic β-hairpin loop for MpNEP2 activity, thus offering a platform for compound design with implications for disease control. Electron paramagnetic resonance and fluorescence assays with MpNEP2 performed in the presence of lipid vesicles of different compositions showed no sign of interaction between the protein and the lipids, implying that MpNEP2 likely requires other anchoring elements from the membrane to promote cytolysis or send death signals.

Shwachman–Bodian–Diamond syndrome is an autosomal recessive genetic syndrome with pleiotropic phenotypes, including pancreatic deficiencies, bone marrow dysfunctions with increased risk of myelodysplasia or leukemia, and skeletal abnormalities. This syndrome has been associated with mutations in the SBDS gene, which encodes a conserved protein showing orthologs in Archaea and eukaryotes. The Shwachman–Bodian–Diamond syndrome pleiotropic phenotypes may be an indication of different cell type requirements for a fully functional SBDS protein. RNA-binding activity has been predicted for archaeal and yeast SBDS orthologs, with the latter also being implicated in ribosome biogenesis. However, full-length SBDS orthologs function in a species-specific manner, indicating that the knowledge obtained from model systems may be of limited use in understanding major unresolved issues regarding SBDS function, namely, the effect of mutations in human SBDS on its biochemical function and the specificity of RNA interaction. We determined the solution structure and backbone dynamics of the human SBDS protein and describe its RNA binding site using NMR spectroscopy. Similarly to the crystal structures of Archaea, the overall structure of human SBDS comprises three well-folded domains. However, significant conformational exchange was observed in NMR dynamics experiments for the flexible linker between the N-terminal domain and the central domain, and these experiments also reflect the relative motions of the domains. RNA titrations monitored by heteronuclear correlation experiments and chemical shift mapping analysis identified a classic RNA binding site at the N-terminal FYSH (fungal, Yhr087wp, Shwachman) domain that concentrates most of the mutations described for the human SBDS.

The human SBDS gene and its yeast ortholog SDO1 encode essential proteins that are involved in ribosome biosynthesis. SDO1 has been implicated in recycling of the ribosomal biogenesis factor Tif6p from pre-66S particles as well as in translation activation of 60S ribosomes. The SBDS protein is highly conserved, containing approximately 250 amino acid residues in animals, fungi and Archaea , while SBDS orthologs of plants and a group of protists contain an extended C-terminal region. In this work, we describe the characterization of the Trypanosoma cruzi SBDS ortholog (TcSBDS). TcSBDS co-fractionates with polysomes in sucrose density gradients, which is consistent with a role in ribosome biosynthesis. We show that TcSBDS contains a C-terminal extension of 200 amino acids that displays the features of intrinsically disordered proteins as determined by proteolytic, circular dichroism and NMR analyses. Interestingly, the C-terminal extension is responsible for TcSBDS–RNA interaction activity in electrophoretic mobility shift assays. This finding suggests that Trypanosomatidae and possibly also other organisms containing SBDS with extended C-terminal regions have evolved an additional function for SBDS in ribosome biogenesis.