O SISTEMA AFRICANO DE PROTEÇÃO DE DIREITOS HUMANOS: UMA ANÁLISE CRÍTICA

Pretende-se, com o presente artigo fazer uma análise crítica do Sistema Africano de Proteção de Direitos Humanos. Para tanto, é necessário tratar da origem e evolução desse sistema, iniciando do período pré-colonial, colonial e até os dias atuais. Ademais, constitui também objetivo do presente trabalho investigar as competências da Comissão Africana de Proteção de Direitos Humanos e dos Povos e da Corte Africana de Proteção de Direitos Humanos e dos Povos, dois órgãos do Sistema Africano de Proteção de Direitos Humanos, para saber até que ponto o sistema africano constitui resposta para as violações de direitos humanos no continente africano

Synthetic organotelluride compounds induce the reversal of Pdr5p mediated fluconazole resistance in Saccharomyces cerevisiae

Background: Resistance to fluconazole, a commonly used azole antifungal, is a challenge for the treatment of fungal infections. Resistance can be mediated by overexpression of ABC transporters, which promote drug efflux that requires ATP hydrolysis. the Pdr5p ABC transporter of Saccharomyces cerevisiae is a well-known model used to study this mechanism of antifungal resistance. the present study investigated the effects of 13 synthetic compounds on Pdr5p.Results: Among the tested compounds, four contained a tellurium-butane group and shared structural similarities that were absent in the other tested compounds: a lateral hydrocarbon chain and an amide group. These four compounds were capable of inhibiting Pdr5p ATPase activity by more than 90%, they demonstrated IC50 values less than 2 M and had an uncompetitive pattern of Pdr5p ATPase activity inhibition. These organotellurides did not demonstrate cytotoxicity against human erythrocytes or S. cerevisiae mutant strains (a strain that overexpress Pdr5p and a null mutant strain) even in concentrations above 100 mu M. When tested at 100 mu M, they could reverse the fluconazole resistance expressed by both the S. cerevisiae mutant strain that overexpress Pdr5p and a clinical isolate of Candida albicans.Conclusions: We have identified four organotellurides that are promising candidates for the reversal of drug resistance mediated by drug efflux pumps. These molecules will act as scaffolds for the development of more efficient and effective efflux pump inhibitors that can be used in combination therapy with available antifungals.Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)University of São Paulo through the NAP-CatSinQ (Research Core in Catalysis and Chemical Synthesis)Univ Fed Rio de Janeiro, CCS, Inst Microbiol Paulo Goes, Dept Microbiol Geral,Lab Bioquim Microbiana, Rio de Janeiro, RJ, BrazilUniv São Paulo, Inst Quim, Dept Quim Fundamental, São Paulo, BrazilInst Fed Educ Ciencia & Tecnol Rio de Janeiro IFR, Rio de Janeiro, RJ, BrazilUniversidade Federal de São Paulo UNIFESP, Inst Ciencias Ambientais Quim & Farmaceut, São Paulo, BrazilUniversidade Federal de São Paulo UNIFESP, Inst Ciencias Ambientais Quim & Farmaceut, São Paulo, BrazilFAPERJ: E-26/111.338/2013FAPESP: 2005/59572-7FAPESP: 2008/55401-1FAPESP: 2010/17228-6FAPESP: 2011/03244-2FAPESP: 2011/11613-8FAPESP: 2012/17093-9CNPq: 470360/2012-7Web of Scienc

SEROLOGICAL DETECTION OF HEPATITIS A VIRUS IN FREE-RANGING NEOTROPICAL PRIMATES (Sapajus spp., Alouatta caraya) FROM THE PARANÁ RIVER BASIN, BRAZIL

Nonhuman primates are considered as the natural hosts of Hepatitis A virus (HAV), as well as other pathogens, and can serve as natural sentinels to investigate epizootics and endemic diseases that are of public health importance. During this study, blood samples were collected from 112 Neotropical primates (NTPs) (Sapajus nigritus and S. cay, n = 75; Alouatta caraya, n = 37) trap-captured at the Paraná River basin, Brazil, located between the States of Paraná and Mato Grosso do Sul. Anti-HAV IgG antibodies were detected in 4.5% (5/112) of NTPs, specifically in 6.7% (5/75) of Sapajus spp. and 0% (0/37) of A. caraya. In addition, all samples were negative for the presence of IgM anti-HAV antibodies. These results suggest that free-ranging NTPs were exposed to HAV within the geographical regions evaluated

Standardizing Clinical Trials Workflow Representation in UML for International Site Comparison

BACKGROUND: With the globalization of clinical trials, a growing emphasis has been placed on the standardization of the workflow in order to ensure the reproducibility and reliability of the overall trial. Despite the importance of workflow evaluation, to our knowledge no previous studies have attempted to adapt existing modeling languages to standardize the representation of clinical trials. Unified Modeling Language (UML) is a computational language that can be used to model operational workflow, and a UML profile can be developed to standardize UML models within a given domain. This paper's objective is to develop a UML profile to extend the UML Activity Diagram schema into the clinical trials domain, defining a standard representation for clinical trial workflow diagrams in UML. METHODS: Two Brazilian clinical trial sites in rheumatology and oncology were examined to model their workflow and collect time-motion data. UML modeling was conducted in Eclipse, and a UML profile was developed to incorporate information used in discrete event simulation software. RESULTS: Ethnographic observation revealed bottlenecks in workflow: these included tasks requiring full commitment of CRCs, transferring notes from paper to computers, deviations from standard operating procedures, and conflicts between different IT systems. Time-motion analysis revealed that nurses' activities took up the most time in the workflow and contained a high frequency of shorter duration activities. Administrative assistants performed more activities near the beginning and end of the workflow. Overall, clinical trial tasks had a greater frequency than clinic routines or other general activities. CONCLUSIONS: This paper describes a method for modeling clinical trial workflow in UML and standardizing these workflow diagrams through a UML profile. In the increasingly global environment of clinical trials, the standardization of workflow modeling is a necessary precursor to conducting a comparative analysis of international clinical trials workflows

Innovating home visiting to mothers and infants by community health workers: an action-oriented guide

Abstract Objectives: to describe the process of development and the structure of an action-oriented guide for home visits (HVs) to mothers and infants by Community Health Workers (CHWs). The guide was adopted in a controlled trial aimed at assessing its efficacy in improving CHWs' performance. Methods: steps to develop the guide included: 1) Review of international and national standards and recommendations for community interventions for maternal and child care; 2) Assessment of perceived needs of CHWs and other Family Health professionals regarding prenatal and postnatal HVs; 3) Identification of elements to construct the guide. Results: the Guide provides action-oriented instructions for 10 HVs during prenatal and postnatal period up to 9 months instead of the 18 HVs currently recommended by Ministry of Health. Specific tasks for each visit including assessment and promotion of early child development (ECD) and an action-oriented risk classification are introduced as standardized operational practice. Conclusions: the described approach to guide construction allows adapting the guide contents to the health system context in Brazil and other countries interested in improving quality of HVs by CHWs. The guide, by identifying tasks to be carried out and actions to be taken at each HV, provides an innovative approach and represents a requisite for a more efficient and effective use of their time

How to avoid the inappropriate use of antibiotics in upper respiratory tract infections? A position statement from an expert panel

Introduction: Bacterial resistance burden has increased in the past years, mainly due to inappropriate antibiotic use. Recently it has become an urgent public health concern due to its impact on the prolongation of hospitalization, an increase of total cost of treatment and mortality associated with infectious disease. Almost half of the antimicrobial prescriptions in outpatient care visits are prescribed for acute upper respiratory infections, especially rhinosinusitis, otitis media, and pharyngotonsillitis. In this context, otorhinolaryngologists play an important role in orienting patients and non-specialists in the utilization of antibiotics rationally and properly in these infections. Objectives: To review the most recent recommendations and guidelines for the use of antibiotics in acute otitis media, acute rhinosinusitis, and pharyngotonsillitis, adapted to our national reality. Methods: A literature review on PubMed database including the medical management in acute otitis media, acute rhinosinusitis, and pharyngotonsillitis, followed by a discussion with a panel of specialists. Results: Antibiotics must be judiciously prescribed in uncomplicated acute upper respiratory tract infections. The severity of clinical presentation and the potential risks for evolution to suppurative and non-suppurative complications must be taken into 'consideration'. Conclusions: Periodic revisions on guidelines and recommendations for treatment of the main acute infections are necessary to orient rationale and appropriate use of antibiotics. Continuous medical education and changes in physicians' and patients' behavior are required to modify the paradigm that all upper respiratory infection needs antibiotic therapy, minimizing the consequences of its inadequate and inappropriate use. (C) 2018 Associacao Brasileira de Otorrinolaringologia e Cirurgia Cervico-Facial. Published by Elsevier Editora Ltda. This is an open access article under the CC BY license.Introdução: A resistência bacteriana a antibióticos nos processos infecciosos é um fato crescente nos últimos anos, especialmente devido ao seu uso inapropriado. Ao longo dos anos vem se tornando um grave problema de saúde pública devido ao prolongamento do tempo de internação, elevação dos custos de tratamento e aumento da mortalidade relacionada às doenças infecciosas. Quase a metade das prescrições de antibióticos em unidades de pronto atendimento é destinada ao tratamento de alguma infecção de vias aéreas superiores, especialmente rinossinusites, otite média aguda supurada e faringotonsilites agudas, sendo que uma significativa parcela dessas prescrições é inapropriada. Nesse contexto, os otorrinolaringologistas têm um papel fundamental na orientação de pacientes e colegas não especialistas, para o uso adequado e racional de antibióticos frente a essas situações clínicas. Objetivos: Realizar uma revisão das atuais recomendações de utilização de antibióticos nas otites médias, rinossinusites e faringotonsilites agudas adaptadas à realidade nacional. Método: Revisão na base PubMed das principais recomendações internacionais de tratamentos das infecções de vias aéreas superiores, seguido de discussão com um painel de especialistas. Resultados: Os antibióticos devem ser utilizados de maneira criteriosa nas infecções agudas de vias aéreas superiores não complicadas, a depender da gravidade da apresentação clínica e dos potenciais riscos associados de complicações supurativas e não supurativas. Conclusões: Constantes revisões a respeito do tratamento das principais infecções agudas são necessárias para que sejam tomadas medidas coletivas no uso racional e apropriado de antibióticos. Somente com orientação e transformações no comportamento de médicos e pacientes é que haverá mudanças do paradigma de que toda infecção de vias aéreas superiores deva ser tratada com antibióticos, minimizando por consequência os efeitos de seu uso inadequado.Univ Fed Rio Grande do Sul, Dept Oftalmol & Otorrinolaringol, Fac Med FAMED, Porto Alegre, RS, BrazilUniv Fed Sao Paulo UNIFESP, Dept Otorrinolaringol & Cirurgia Cabeca & Pescoco, EPM, Sao Paulo, SP, BrazilUniv Estadual Campinas, UNICAMP, Dept Otorrinolaringol & Oftalmol, Campinas, SP, BrazilUniv Sao Paulo, FM, Disciplina Otorrinolaringol, Sao Paulo, SP, BrazilUniv Sao Paulo, FM, Otorrinolaringol, Sao Paulo, SP, BrazilHosp Infantil Sabara, Otorrinolaringol, Sao Paulo, SP, BrazilHosp Paranaense Otorrinolaringol IPO, Inst Paranaense Otorrinolaringol, Curitiba, Parana, BrazilFac Ciencias Med Santa Casa de Sao Paulo, Sao Paulo, SP, BrazilUniv Fed Pernambuco UFPE, Dept Cirurgia, Div Otorrinolaringol, Recife, PE, BrazilUniv Luterana Brasil, Fac Med, Porto Alegre, RS, BrazilUniv Sao Paulo, FM, Sao Paulo, SP, BrazilHosp Albert Einstein, Sao Paulo, SP, BrazilUniv Sao Paulo, FMRP, Dept Oftalmol Otorrinolaringol & Cirurgia Cabeca, Ribeirao Preto, SP, BrazilUniv Fed Ciencias Saude Porto Alegre, Hosp Crianca St Antonio, Serv Otorrinolaringol Pediat, Porto Alegre, RS, BrazilUniv Estado Rio De Janeiro, Fac Ciencias Med, Disciplina Otorrinolaringol, Rio De Janeiro, RJ, BrazilUniv Fed Goias, Goiania, Go, BrazilPontificia Univ Catolica Goias PUC GO, Goiania, Go, BrazilCtr Univ Anapolis, Anapolis, Go, BrazilUniv Fed Sao Paulo UNIFESP, Dept Otorrinolaringol & Cirurgia Cabeca & Pescoco, EPM, Sao Paulo, SP, BrazilSciEL

Subcellular Localization of Hexokinases I and II Directs the Metabolic Fate of Glucose

The first step in glucose metabolism is conversion of glucose to glucose 6-phosphate (G-6-P) by hexokinases (HKs), a family with 4 isoforms. The two most common isoforms, HKI and HKII, have overlapping tissue expression, but different subcellular distributions, with HKI associated mainly with mitochondria and HKII associated with both mitochondrial and cytoplasmic compartments. Here we tested the hypothesis that these different subcellular distributions are associated with different metabolic roles, with mitochondrially-bound HK's channeling G-6-P towards glycolysis (catabolic use), and cytoplasmic HKII regulating glycogen formation (anabolic use).To study subcellular translocation of HKs in living cells, we expressed HKI and HKII linked to YFP in CHO cells. We concomitantly recorded the effects on glucose handling using the FRET based intracellular glucose biosensor, FLIPglu-600 mM, and glycogen formation using a glycogen-associated protein, PTG, tagged with GFP. Our results demonstrate that HKI remains strongly bound to mitochondria, whereas HKII translocates between mitochondria and the cytosol in response to glucose, G-6-P and Akt, but not ATP. Metabolic measurements suggest that HKI exclusively promotes glycolysis, whereas HKII has a more complex role, promoting glycolysis when bound to mitochondria and glycogen synthesis when located in the cytosol. Glycogen breakdown upon glucose removal leads to HKII inhibition and dissociation from mitochondria, probably mediated by increases in glycogen-derived G-6-P.These findings show that the catabolic versus anabolic fate of glucose is dynamically regulated by extracellular glucose via signaling molecules such as intracellular glucose, G-6-P and Akt through regulation and subcellular translocation of HKII. In contrast, HKI, which activity and regulation is much less sensitive to these factors, is mainly committed to glycolysis. This may be an important mechanism by which HK's allow cells to adapt to changing metabolic conditions to maintain energy balance and avoid injury

Inference of gene regulatory networks from time series by Tsallis entropy

Background: The inference of gene regulatory networks (GRNs) from large-scale expression profiles is one of the most challenging problems of Systems Biology nowadays. Many techniques and models have been proposed for this task. However, it is not generally possible to recover the original topology with great accuracy, mainly due to the short time series data in face of the high complexity of the networks and the intrinsic noise of the expression measurements. In order to improve the accuracy of GRNs inference methods based on entropy (mutual information), a new criterion function is here proposed. Results: In this paper we introduce the use of generalized entropy proposed by Tsallis, for the inference of GRNs from time series expression profiles. The inference process is based on a feature selection approach and the conditional entropy is applied as criterion function. In order to assess the proposed methodology, the algorithm is applied to recover the network topology from temporal expressions generated by an artificial gene network (AGN) model as well as from the DREAM challenge. The adopted AGN is based on theoretical models of complex networks and its gene transference function is obtained from random drawing on the set of possible Boolean functions, thus creating its dynamics. On the other hand, DREAM time series data presents variation of network size and its topologies are based on real networks. The dynamics are generated by continuous differential equations with noise and perturbation. By adopting both data sources, it is possible to estimate the average quality of the inference with respect to different network topologies, transfer functions and network sizes. Conclusions: A remarkable improvement of accuracy was observed in the experimental results by reducing the number of false connections in the inferred topology by the non-Shannon entropy. The obtained best free parameter of the Tsallis entropy was on average in the range 2.5 <= q <= 3.5 (hence, subextensive entropy), which opens new perspectives for GRNs inference methods based on information theory and for investigation of the nonextensivity of such networks. The inference algorithm and criterion function proposed here were implemented and included in the DimReduction software, which is freely available at http://sourceforge.net/projects/dimreduction and http://code.google.com/p/dimreduction/.Fundacao de Amparo e Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)Coordenacao de Aperfeicofamento de Pessoal de Nivel Superior (CAPES)Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq