Contemporary registries on P2Y12 inhibitors in patients with acute coronary syndromes in Europe: overview and methodological considerations

Patient registries play an important role in cardiology. They provide data not found in randomised controlled trials, including valuable information on drug use and clinical outcomes. They allow an evaluation as to what extent guidelines are followed in practice.The Platelet Inhibition Registry in ACS EvalUation Study (PIRAEUS) project is an initiative of registry holders who manage national or international registries observing patients with acute coronary syndromes (ACS). The aim of PIRAEUS is to compare and combine available information/insights from various European ACS registries with a focus on P2Y12 inhibitors.The present publication introduces the 17 participating registries in narrative and tabular form

The enzyme mechanism of a de novo designed and evolved aldolase

The combination of computational enzyme design and laboratory evolution is a successful strategy for the development of biocatalysts with non-natural function, one example being the artificial retroaldolase RA95.1,2 This enzyme utilizes amine catalysis via a reactive lysine residue to cleave the unnatural aldol substrate methodol (Figure 1A). The low initial catalytic activity of the computational design was improved tremendously over many rounds of directed evolution, yielding an efficient biocatalyst for both aldol cleavage as well as synthesis with rate acceleration and stereoselectivity comparable to natural aldolases (Figure 1B).3,4 Key to this success was an ultrahigh-throughput (uHTP) screening technique applied for the late stages of optimization.4 In this work, we analyzed changes in enzyme mechanism along the evolutionary trajectory of RA95 that led to more efficient catalysis. To that end, we determined the rate-limiting step for different enzyme variants by probing individual steps of the aldolase mechanism kinetically. We found a shift towards product release being overall rate-limiting for aldol cleavage catalyzed by highly evolved variants of RA95. Specifically, the conversion between Schiff base and enamine intermediate formed from acetone, a (de-)protonation-dependent process, is the slowest step we probed. Our results indicate that uHTP screening is essential to efficiently evolve a multi-step enzyme mechanism, as it allows the optimization of several mechanistic steps in parallel. By comparing our findings to kinetic and structural studies on natural aldolases, we provide valuable feedback to improve future laboratory evolution approaches as well as the success rate of computational enzyme design. Please click Additional Files below to see the full abstract

Inferior ST-Elevation Myocardial Infarction Associated with Takotsubo Cardiomyopathy

Takotsubo cardiomyopathy (TCM) is usually characterized by transient left ventricular apical ballooning. Due to the clinical symptoms which include chest pain, electrocardiographic changes, and elevated myocardial markers, Takotsubo cardiomyopathy is frequently mimicking ST-elevation myocardial infarction in the absence of a significant coronary artery disease. Otherwise an acute occlusion of the left anterior descending coronary artery can produce a typical Takotsubo contraction pattern. ST-elevation myocardial infarction (STEMI) is frequently associated with emotional stress, but to date no cases of STEMI triggering TCM have been reported. We describe a case of a female patient with inferior ST-elevation myocardial infarction complicated by TCM

Characterizing Active Site Conformational Heterogeneity along the Trajectory of an Enzymatic Phosphoryl Transfer Reaction

States along the phosphoryl transfer reaction catalyzed by the nucleoside monophosphate kinase UmpK were captured and changes in the conformational heterogeneity of conserved active site arginine side-chains were quantified by NMR spin-relaxation methods. In addition to apo and ligand-bound UmpK, a transition state analog (TSA) complex was utilized to evaluate the extent to which active site conformational entropy contributes to the transition state free energy. The catalytically essential arginine side-chain guanidino groups were found to be remarkably rigid in the TSA complex, indicating that the enzyme has evolved to restrict the conformational freedom along its reaction path over the energy landscape, which in turn allows the phosphoryl transfer to occur selectively by avoiding side reactions

A percepção dos professores quanto a participação e ausência da família na vida escolar das crianças

Monografia (especialização)—Universidade de Brasília, Ministério da Educação, Centro de Estudos Avançados Multidisciplinares, Centro de Formação Continuada de Professores, Secretaria de Educação do Distrito Federal, Escola de Aperfeiçoamento de Profissionais da Educação, Curso de Especialização em Coordenação Pedagógica, 2013.A presente pesquisa surgiu de uma inquietação da pesquisadora em relação a ausência familiar na vida escolar dos alunos, para tanto a pesquisa objetivou identificar como os professores da Escola Classe 01 do Riacho Fundo II percebem tanto a participação familiar na vida escolar, quanto as causas e as consequências da ausência familiar na vida escolar dos alunos. Primeiramente a pesquisa fundamentou-se teoricamente nos autores Heloísa Szymanski (2007), Adriana Varani (2010), Bárbara Caiado Mendes (2010), José Reinaldo Alves (2010), dentre outros que embasam seus estudos e pesquisas na área educacional. Construído o referencial teórico, a pesquisa utilizou-se da abordagem qualitativa para a análise das informações obtidas por meio de questionário. Constatou-se que os professores da Escola Classe 01- Riacho Fundo II possuem experiência e sabem detectar os aspectos ligados à relação família versus escola, pois em suas respostas houve muitas consonâncias com o que os autores consultados relataram sobre tais aspectos, pois após a realização da pesquisa foi realizado um confronto entre as ideias dos autores consultados e as respostas dos professores pesquisados. Houve maior consonância, porém com as autoras Dessen e Polônia (2005), Maturano (1999) e Mendes (2010). Reconhecendo que a questão da ausência familiar na vida escolar dos alunos é um problema que acarreta vários outros problemas como o desinteresse com os estudos, a indisciplina, a falta de compromisso com os estudos, a dificuldade de aprendizagem e consequentemente o fracasso escolar. A pesquisa deixa claro que somente conhecer os aspectos da ausência familiar não resolve os problemas que lhe advém, mas já é um bom início, pois fornece caminhos por onde trilhar para a busca de soluções

Simulação dinâmica de uma Torre de Stripper.

Um dos efluentes gerados na indústria de cloro e soda é uma corrente ácida (água saturada de cloro). Esta corrente deve passar por um sistema de tratamento antes de ser descartado, devido ao potencial de dano que este pode causar à flora e à fauna marinha, além de infringir as regulamentações ambientais. Visando reduzir o consumo de energia e atender à especificação do efluente, o objetivo deste trabalho é realizar e avaliar a simulação dinâmica de um sistema de tratamento de efluente ácido. O sistema estudado é composto por uma coluna de stripper e um trocador de calor que pré aquece a corrente de alimentação. O estudo se concentrou em avaliar o comportamento do sistema no estado estacionário e dinâmico frente a alterações nas condições de operação do trocador de calor. As simulações foram realizadas no AspenTM e validados com dados da planta industrial. De acordo com os resultados, reduzindo a eficiência de troca de calor do trocador leva no aumento do consumo de energia e o efluente fica fora das especificações. Desta forma, é muito importante manter a eficiência do trocador de acordo com a de projeto e os controladores sintonizados.One of the effluents generated by chlor-alkali plant is an acid stream (saturated water chlorine). This stream must pass through a treatment system before being discarded because of damage potential that this may cause to the flora and marine fauna, in addition to breaching environmental regulations. In order to reduce energy consumption and meet the effluent specification, the objective is to implement and evaluate the dynamic simulation of an acid wastewater treatment system. The system is composed of a column stripper and a heat exchanger that heats the pre feed stream. The study focused on evaluating the system behavior in the steady state and dynamic against changes in operating conditions of the heat exchanger. The simulations were accomplished by the simulator Aspen™ and validated with data from industrial plant. According to the results, reducing the efficiency of heat exchanger can make the power consumption increase and the effluent is out of specification. This way, it is very important to keep the heat exchange efficiency according to design and tuned controls

Practical approach on frail older patients attended for acute heart failure

Acute heart failure (AHF) is a multi-organ dysfunction syndrome. In addition to known cardiac dysfunction, non-cardiac comorbidity, frailty and disability are independent risk factors of mortality, morbidity, cognitive and functional decline, and risk of institutionalization. Frailty, a treatable and potential reversible syndrome very common in older patients with AHF, increases the risk of disability and other adverse health outcomes. This position paper highlights the need to identify frailty in order to improve prognosis, the risk-benefits of invasive diagnostic and therapeutic procedures, and the definition of older-person-centered and integrated care plans