Learning: New Strategy for Humanized Digital Medical Education and Training in Cardiology. / Virtual Case-Based Learning: Nova Estratégia de Ensino e de Treinamento Médico Digital Humanizado em Cardiologia.

BACKGROUND: The consolidation of new educational paradigms requires the implementation of innovative strategies to transform students into competent professionals. OBJECTIVES: To assess knowledge and satisfaction of medical students before and after the use of a new humanized digital model of active learning, called virtual case-based learning (VCBL). METHODS: This was a descriptive, documentary analysis of the teaching-learning process of medical students. Data obtained from theoretical knowledge assessment and satisfaction evaluation questionnaires applied in 2018 and 2019 were analyzed, and the new VCBL was compared with the traditional active methodology PBL (problem-based learning). Descriptive and association analyses were made using the Statistical Package for the Social Sciences. RESULTS: A total of 167 evaluation forms administered to medical students were analyzed. In the evaluation of theoretical knowledge, the 2018 and the 2019 student groups had a mean of 41.7% and 73.3%, respectively (p<0.001). Among the students who responded to the satisfaction evaluation form, 76.0% gave the highest rating to question one, and 83.0% to question two. Nearly 70.0% of students positively evaluated knowledge acquisition with the Paciente 360 platform; 78.0% reported to feel prepared for working in outpatient care; and 94.0% positively evaluated the new method. CONCLUSION: In this initial study, the results indicate that the new active method for humanized digital medical education, the VCBL, can help in the betterment of the teaching-learning process, promoting knowledge and satisfaction by the students.

FUNDAMENTO: A consolidação de novos paradigmas educacionais exige a implantação de estratégias inovadoras com potencial de transformar estudantes em profissionais competentes. OBJETIVOS: Analisar o conhecimento e a satisfação de estudantes antes e após a utilização de uma nova metodologia ativa de ensino médico de modelo digital humanizado chamada Virtual Case-Based Learning (VCBL). MÉTODOS: Estudo descritivo com análise documental sobre o processo de ensino-aprendizagem de estudantes de medicina. Dados obtidos da avaliação de conhecimento teórico e do instrumento de satisfação dos alunos nos anos de 2018 e 2019 foram analisados, e a nova metodologia proposta VCBL foi comparada com a metodologia ativa de ensino tradicional, o Problem-Based Learning (PBL). As análises descritivas e de associação foram realizadas utilizando o programa Statistical Package for the Social Sciences. RESULTADOS: Foram analisados 167 documentos aplicados a estudantes de medicina. Em relação à avaliação do conhecimento teórico, os alunos avaliados em 2018 obtiveram média 41,7%, comparados aos alunos de 2019 que alcançaram 73,3% (p<0,001). Entre os estudantes submetidos à avaliação da satisfação com a metodologia de aprendizagem proposta, 76,0% pontuaram o valor máximo para a questão um, e 83,0% para a questão número dois. Cerca de 70,0% dos estudantes classificaram positivamente o aprendizado adquirido após utilização da plataforma Paciente 360; 78,0% responderam que se sentem preparados para o atendimento ambulatorial; e 94,0% pontuaram de forma positiva a metodologia empregada. CONCLUSÃO: Neste estudo inicial, os resultados indicaram que a nova ferramenta em metodologia ativa de ensino médico digital humanizado, o VCBL, pode auxiliar no aprimoramento do processo de ensino-aprendizagem, proporcionando conhecimento e satisfação dos estudantes.

Virtual Case-Based Learning: Nova Estratégia de Ensino e de Treinamento Médico Digital Humanizado em Cardiologia / Learning: New Strategy for Humanized Digital Medical Education and Training in Cardiology

Resumo Fundamento A consolidação de novos paradigmas educacionais exige a implantação de estratégias inovadoras com potencial de transformar estudantes em profissionais competentes. Objetivos Analisar o conhecimento e a satisfação de estudantes antes e após a utilização de uma nova metodologia ativa de ensino médico de modelo digital humanizado chamada Virtual Case-Based Learning (VCBL). Métodos Estudo descritivo com análise documental sobre o processo de ensino-aprendizagem de estudantes de medicina. Dados obtidos da avaliação de conhecimento teórico e do instrumento de satisfação dos alunos nos anos de 2018 e 2019 foram analisados, e a nova metodologia proposta VCBL foi comparada com a metodologia ativa de ensino tradicional, o Problem-Based Learning (PBL). As análises descritivas e de associação foram realizadas utilizando o programa Statistical Package for the Social Sciences. Resultados Foram analisados 167 documentos aplicados a estudantes de medicina. Em relação à avaliação do conhecimento teórico, os alunos avaliados em 2018 obtiveram média 41,7%, comparados aos alunos de 2019 que alcançaram 73,3% (p<0,001). Entre os estudantes submetidos à avaliação da satisfação com a metodologia de aprendizagem proposta, 76,0% pontuaram o valor máximo para a questão um, e 83,0% para a questão número dois. Cerca de 70,0% dos estudantes classificaram positivamente o aprendizado adquirido após utilização da plataforma Paciente 360; 78,0% responderam que se sentem preparados para o atendimento ambulatorial; e 94,0% pontuaram de forma positiva a metodologia empregada. Conclusão Neste estudo inicial, os resultados indicaram que a nova ferramenta em metodologia ativa de ensino médico digital humanizado, o VCBL, pode auxiliar no aprimoramento do processo de ensino-aprendizagem, proporcionando conhecimento e satisfação dos estudantes.

Abstract Background The consolidation of new educational paradigms requires the implementation of innovative strategies to transform students into competent professionals. Objectives To assess knowledge and satisfaction of medical students before and after the use of a new humanized digital model of active learning, called virtual case-based learning (VCBL). Methods This was a descriptive, documentary analysis of the teaching-learning process of medical students. Data obtained from theoretical knowledge assessment and satisfaction evaluation questionnaires applied in 2018 and 2019 were analyzed, and the new VCBL was compared with the traditional active methodology PBL (problem-based learning). Descriptive and association analyses were made using the Statistical Package for the Social Sciences. Results A total of 167 evaluation forms administered to medical students were analyzed. In the evaluation of theoretical knowledge, the 2018 and the 2019 student groups had a mean of 41.7% and 73.3%, respectively (p<0.001). Among the students who responded to the satisfaction evaluation form, 76.0% gave the highest rating to question one, and 83.0% to question two. Nearly 70.0% of students positively evaluated knowledge acquisition with the Paciente 360 platform; 78.0% reported to feel prepared for working in outpatient care; and 94.0% positively evaluated the new method. Conclusion In this initial study, the results indicate that the new active method for humanized digital medical education, the VCBL, can help in the betterment of the teaching-learning process, promoting knowledge and satisfaction by the students.

Final Demonstration of the Co-Identity of Lipiarmycin A3 and Tiacumicin B (Fidaxomicin) through Single Crystal X-ray Analysis.

Lipiarmycin A3 and tiacumicin B possess the same chemical structure and have been considered identical till recently, when some authors have suggested the possibility of a minor difference between the chemical structures of the two antibiotics. In this work we performed a comparative X-ray analysis of lipiarmycin A3 and tiacumicin B. Although the commercial samples of the aforementioned compounds crystallize into two different crystal systems-evidently due to the different crystallization conditions-their chemical structures are identical. These results confirmed the previous assigned chemical structure of lipiarmycin A3 and its absolute configuration as well as its co-identity with the chemical structure of tiacumicin B, providing the definitive proof that these pharmaceutical compounds are identical in all respects.

The Co-identity of Lipiarmycin A3 and Tiacumicin B.

The co-identity of the antibiotics lipiarmycin A3 obtained from Actinoplanes deccanensis and tiacumicin B obtained from Dactylosporangium aurantiacum was unambiguously demonstrated through a number of experimental means. Spectroscopic analyses performed on both the antibiotics themselves and on their derivatives showed no difference between the two series of compounds. Moreover, unambiguous confirmation of the postulated identity of the two compounds was achieved by chemical degradation of lipiarmycin A3 and isolation of (3S,4R)-pentane-1,3,4-triol triacetate whose relative configuration was assigned by comparison with the authentic erythro and threo pentane-1,3,4-triol triacetates, obtained by chemical synthesis.

Investigation of the stereochemical course of ene reductase-catalysed reactions by deuterium labelling.

The stereoselective reduction of suitably substituted C═C bonds mediated by enzymes, called ene reductases, has received great attention in the last decade. Some successful applications of this biocatalysed procedure to the synthesis of chiral active pharmaceutical ingredients have been reported in the literature. The generation of suitable models to be used for predicting the stereochemical outcome of this kind of reductions is a challenging task. In the last years we have exploited deuterium labelling to investigate the stereochemical course of the enzyme-mediated reductions of a wide collection of substrates belonging to well-defined chemical classes. The results of this research have allowed us to draw conclusions on the relationship between the structural characteristics of the substrate and the binding mode it adopts in the enzyme active site. The collected data can be exploited to create an empirical model to rationalise and predict the stereoselectivity of old yellow enzyme (OYE)-catalysed reductions.

The co-identity of lipiarmycin A3 and tiacumicin B.

The co-identity of the antibiotics lipiarmycin A3 obtained from Actinoplanes deccanensis and tiacumicin B obtained from Dactylosporangium aurantiacum was unambiguously demonstrated through a number of experimental means. Spectroscopic analyses performed on both the antibiotics themselves and on their derivatives showed no difference between the two series of compounds. Moreover, unambiguous confirmation of the postulated identity of the two compounds was achieved by chemical degradation of lipiarmycin A3 and isolation of (3S,4R)-pentane-1,3,4-triol triacetate whose relative configuration was assigned by comparison with the authentic erythro and threo pentane-1,3,4-triol triacetates, obtained by chemical synthesis.

Como reduzir o número de não respondedores na terapia da ressincronização cardíaca? / How to reduce nonresponders in cardiac resynchronization therapy?

A Terapia de Ressincronização Cardíaca (TRC) já foi avaliada em numerosos estudos clínicos randomizados. Comparada à terapia médica otimizada (TMO) isoladamente ou associada ao implante adicional de um cardioversor desfibrilador implantável (CDI) demonstrou alterar de maneira consistente a evolução da insuficiência cardíaca (IC), levando a benefícios clínicos de longo prazo. A despeito do sucesso da TRC e da recente expansão do seu papel no tratamento de pacientes com IC em classes funcionais menos avançadas, a taxa de não resposta situa-se em torno de 30% utilizando-se critérios clínicos e ecocardiográficos. Permanecem ainda limitações inerentes à tecnologia e ao implante do eletrodo no ventrículo esquerdo. Esta revisão abordará os principais fatores determinantes da resposta à TRC, e discutirá as principais estratégias na identificação de fatores da boa e má resposta tanto no pré, trans e pós-operatório com a finalidade de reduzir o índice de não respondedores.

Intermittent simulated moving bed chromatographic separation of (RS,RS)-2-(2,4-difluorophenyl)butane-1,2,3-triol.

The pharmaceutically relevant compound (RS,RS)-2-(2,4-difluorophenyl)butane-1,2,3-triol, an important intermediate in the production of different antifungal drugs, is synthesized in racemic form. For further use in the laboratory the compound has to be separated into its pure enantiomers. This work describes the different steps required to set up a chiral separation using intermittent simulated moving bed chromatography (I-SMB). Furthermore, the effect of feed concentration on the choice of the operating conditions is presented in the frame of the triangle theory. The experiments are carried out at increasing total feed concentration ranging from 3 to 15 g/L. The results demonstrate that a successful I-SMB separation could be carried out thus separating 4.5 g of the racemic mixture and fulfilling the specified purity specification of 98% for both enantiomers.

Validating a strategy for molecular dynamics simulations of cyclodextrin inclusion complexes through single-crystal X-ray and NMR experimental data: a case study.

A theoretical and experimental study about the formation and structure of the inclusion complex (-)-menthyl-O-beta-D-glucopyranoside 1 with beta-cyclodextrin (beta-CD) 2 is presented as paradigmatic case study to test the results of molecular dynamics (MD) simulations. The customary methodological approach-the use of experimental geometrical parameters as restraints for MD runs-is logically reversed and the calculated structures are a posteriori compared with those obtained from NMR spectroscopy in D(2)O solution and single crystal X-ray diffraction so as to validate the simulation procedure. The guest molecule 1 allows for a broad repertoire of intermolecular interactions (dipolar, hydrophobic, hydrogen bonds) concurring to stabilize the host-guest complex, thus providing the general applicability of the simulation procedure to cyclodextrin physical chemistry. Many starting geometries of the host-guest association were chosen, not assuming any a priori inclusion. The simulation protocol, involving energy minimization and MD runs in explicit water, yielded four possible inclusion geometries, ruling out higher-energy outer adducts. By analysis of the average energy at room temperature, the most stable geometry in solution was eventually obtained, while the kinetics of formation showed that it is also kinetically favored. The reliability of such geometry was thoroughly checked against the NOE distances via the pair distribution functions, that is, the statistical distribution of intermolecular distances among selected diagnostic atoms calculated from the MD trajectories at room temperature. An analogous procedure was adopted both with implicit solvent and in vacuo. The most stable geometry matched that found with explicit solvent but major differences were observed in the relative stability of the metastable complexes as a consequence of the lack of hydration on the polar moiety of the guest. Finally, a control set of geometrical parameters of the thermodynamically favored complex matched the corresponding one obtained from the X-ray structure, while local conformational differences were indicative of packing effects.

Applications of biocatalysis in fragrance chemistry: the enantiomers of alpha-, beta-, and gamma-irones.

The history of iris extracts, and of the isolation and enzyme-mediated synthesis of their odoriferous principle, the "irones", will be used to describe the improvement brought about by chemistry and biocatalysis in the development of natural fragrances. In particular, this tutorial review will discuss how the progress in the field of enzyme chemistry allowed the optimisation of accelerated procedures for the preparation of natural irone extracts, and the synthesis of all the ten isomers of irone, starting from commercial irone alpha.

Monitoring the synthetic procedures of commercial drugs by 2H NMR spectroscopy: the case of ibuprofen and naproxen.

We determined the D/H isotope ratios of some ibuprofen and naproxen samples by (2)H NMR spectroscopy. Some of these values were found to be useful for collecting hints on the synthetic procedures employed to prepare these drugs. Site-specific isotope ratio analysis shows great potentials in the fight against patent infringement.

Impurities of tazarotene: isolation and structural characterisation.

Two impurities showing structures 5 and 6 were isolated and characterised by means of NMR analysis, during the optimisation of a synthetic procedure to tazarotene. Impurity 5, i.e. ethyl 6-((4,4-dimethyl-4H-thiochromen-6-yl)ethynyl)nicotinate, was a by-product of the reduction of the intermediate sulfoxide 7 with PCl(3). Impurity 6, i.e. 1,4-bis(4,4-dimethylthiochroman-6-yl)buta-1,3-diyne, was due to a side reaction of the Sonogashira coupling.

Traceability of synthetic drugs by position-specific deuterium isotope ratio analysis: the case of Prozac and the fluoxetine generics.

Samples of fluoxetine of different origin were submitted to natural abundance 2H NMR spectroscopy. The deuterium content at the various sites of the molecule was found to depend on its synthetic history. Hints on the synthetic procedure can be obtained by comparison with standard compounds, whose synthesis is known. These preliminary results give an idea of the potential of site-specific isotope ratio analysis in the fight against patent infringement and drug counterfeiting.

Recent advances in the benzannulation of substituted 3-alkoxycarbonyl-3,5-hexadienoic acids and 3-alkoxycarbonylhex-3-en-5-ynoic acids to polysubstituted aromatics.

The benzannulation reactions of substituted 3-alkoxycarbonyl-3,5-hexadienoic and 3-alkoxycarbonylhex-3-en-5-ynoic acids offer a straightforward access to various polysubstituted aromatic compounds. The process is very flexible, and can be applied to the regiospecific preparation of oligoaryls, naphthalenes, ring-fused heterocycles, chiral tetrahydronaphthalenes, C-aryl-glycosides and many natural products of different structure. In this Concept article, we highlight the potential of this annulation reaction by illustration of our recent contribution to this field, as well as the studies previous reported by others.

Isolation and characterisation of impurities in adapalene.

Three impurities of structure 2-4 were isolated and characterised during the optimisation of a synthetic procedure to adapalene. Impurity 1 was a by-product of the Friedel-Crafts reaction of adamantanol with 4-bromoanisole. Impurities 3 and 4 were due to side reactions of the final Negishi coupling.

Isolation and characterisation of a phenolic impurity in a commercial sample of duloxetine.

A phenolic impurity of duloxetine hydrochloride was isolated and characterised (MS, NMR, X-ray-analysis).