Cucurbiturilos como contentores moleculares: Estratégias de encapsulação de endoperóxidos com atividade antimalárica

No desenvolvimento de fármacos um dos principais desafios corresponde à criação de formulações estáveis que consigam alcançar o alvo terapêutico in vivo. Além da formulação de novos fármacos, o encapsulamento dos já existentes em contentores moleculares representa uma das estratégias utilizadas para otimizar a resposta terapêutica e minimizar os efeitos adversos. Alguns sistemas macrocíclicos têm sido explorados como contentores moleculares, evidenciando capacidade para encapsular agentes terapêuticos através de interações não covalentes. Os cucurbiturilos, de abreviatura CB[n], surgiram recentemente como uma nova classe de contentores moleculares capazes de encapsular uma grande variedade de moléculas, incluindo corantes fluorescentes, fármacos e moléculas biológicas. A malária é uma doença infeciosa causada por parasitas do género Plasmodium, transmitidos ao ser humano através da picada de mosquitos fêmea do género Anopheles, afetando principalmente áreas tropicais e sub-tropicais. São conhecidas 5 espécies de Plasmodium que infetam o ser humano, sendo P. vivax e P. falciparum responsáveis pela quase totalidade dos casos de malária, a nível mundial. Dados da OMS indicam que, em 2020, o número total de casos de malária rondava 241 milhões e o número de mortes por malária foi de ca. 627.000, um aumento de ca. 69.000 mortes em relação ao ano anterior. Este facto é atribuído, essencialmente, ao desenvolvimento de resistências pelo parasita aos fármacos antimaláricos em uso, incluindo às terapêuticas de primeira linha baseadas em artemisinina. Assim, é urgente o desenvolvimento de terapêuticas com propriedades farmacológicas melhoradas, nomeadamente com eficácia contra estirpes de P. falciparum resistentes. Posto isto, a presente dissertação aborda o potencial dos cucurbiturilos para o encapsulamento de endoperóxidos com atividade antimalárica. Na primeira parte apresenta-se uma revisão bibliográfica sobre a utilização de cucurbiturilos na encapsulação de fármacos. Na segunda parte descreve-se o trabalho experimental realizado, versando a síntese de um endoperóxido com propriedades antimaláricas e a sua encapsulação em CB[7], incluindo resultados preliminares de estudos in vitro da atividade antiplasmodial.During the development of drugs, one of the main challenges corresponds to the creation of stable formulations that can reach the therapeutic target in vivo. In addition to the formulation of new drugs, the encapsulation of existing ones in molecular containers represents one of the strategies used to optimize therapeutic response and minimize adverse effects. Some macrocyclic systems have been exploited as molecular containers, showing ability to encapsulate therapeutic agents through non-covalent interactions. Cucurbiturils, abbreviated as CB[n], recently emerged as a new class of molecular containers capable of encapsulating a wide variety of guest molecules, including fluorescent dyes, drugs, and biological molecules. Malaria is an infectious disease caused by Plasmodium parasites and transmitted to humans through the bites of infected female Anopheles mosquitoes, mainly affecting tropical and sub-tropical areas. There are 5 species of Plasmodium that can infect humans, being P. vivax and P. falciparum responsible for almost all cases of malaria worldwide. According to WHO, in 2020, there were 241 million cases of malaria and the estimated number of malaria deaths stood at 627.000, an increase of 69.000 deaths compared to the previous year. This fact is essentially attributed to the development of resistance by the Plasmodium parasites to the antimalarial drugs in use, including first-line treatment based on artemisinin combination therapies. Therefore, the development of therapeutics with improved pharmacological properties that are effective against resistant P. falciparum strains is crucial. As such, the present dissertation addresses the potential of cucurbiturils for the encapsulation of endoperoxides with antimalarial activity. The first part of this dissertation offers a bibliographic review on the use of cucurbiturils in drug encapsulation, and the second part describes the experimental work undertaken towards approaching the encapsulation of an endoperoxide with antimalarial properties in CB[7]. Preliminary data on in vitro antiplasmodial activity is provided

The Development of Coherent Speech in Elementary School Students in The Process of Constructive and Artistic Activity

The article examines the development of speech in elementary school students. The research objective is to determine the status of coherent speech development in 3rd-grade students in the process of constructive and artistic activity. The article defines the criteria (structural and compositional, communicative and productive, and communicative and creative), indicators, and levels of development of coherent speech in elementary school students in the process of constructive and artistic activity. Each criterion includes a group of qualitative content-disclosing indicators and characterizes the achievements of students in the intended type of activity. Based on this, the authors have developed a methodological tool that allows them to diagnose coherent speech development in 3rd-grade students in the process of constructive and artistic activity and to conduct a precise quantitative differentiation by high, sufficient, medium, and low levels of coherent speech formation with specific characteristics for qualitative measurements that open up prospects for the development of appropriate effective measures for improving the quality of training students for such activity

El desarrollo del discurso coherente en estudiantes de primaria en el proceso de actividad constructiva y artística

The article examines the development of speech in elementary school students. The research objective is to determine the status of coherent speech development in 3rd-grade students in the process of constructive and artistic activity. The article defines the criteria (structural and compositional, communicative and productive, and communicative and creative), indicators, and levels of development of coherent speech in elementary school students in the process of constructive and artistic activity. Each criterion includes a group of qualitative content-disclosing indicators and characterizes the achievements of students in the intended type of activity. Based on this, the authors have developed a methodological tool that allows them to diagnose coherent speech development in 3rd-grade students in the process of constructive and artistic activity and to conduct a precise quantitative differentiation by high, sufficient, medium, and low levels of coherent speech formation with specific characteristics for qualitative measurements that open up prospects for the development of appropriate effective measures for improving the quality of training students for such activity.El artículo examinael desarrollo del habla en estudiantes de primaria. El objetivo de la investigación es determinar el estado del desarrollo coherente del habla en estudiantes de tercer grado en el proceso de actividad constructiva y artística. El artículo define los criterios (estructurales y compositivos, comunicativos y productivos, y comunicativos y creativos), indicadores y niveles de desarrollo del discurso coherente en estudiantes de primaria en el proceso de actividad constructiva y artística. Cada criterio incluye un grupo de indicadores cualitativos de divulgación de contenido y caracteriza los logros de los estudiantes en el tipo de actividad prevista. En base a esto, los autores han desarrollado una herramienta metodológica que les permite diagnosticar el desarrollo coherente del habla en estudiantes de tercer grado en el proceso de actividad constructiva y artística y llevar a cabo una diferenciación cuantitativa precisa por niveles altos, suficientes, medios y bajos de formación coherente del habla con características específicas para mediciones cualitativas que abren perspectivas para el desarrollo de medidas efectivas apropiadas para mejorar la calidad de la capacitación de los estudiantes para dicha actividad

La preparación de los futuros especialistas de educación preescolar para la autorrealización creativa en la actividad profesional

The article is devoted to the issue of future specialists of preschool education training to creative self-realization in professional activity. The authors of the article reveal the pedagogical diagnostics of readiness to creative self-realization in professional activity of higher educational institutions’ students. The purpose of the study is to reveal the results of pedagogical diagnostics of future specialists of preschool education readiness to creative self-realization in professional activity. A diagnostic methodology and criteria of future specialists of preschool education to creative self-realization in professional activity readiness has developed. The criteria of future specialists of preschool education to creative self-realization in professional activity readiness are: motivational and valuable, creative activity, assessment and reflective. Each criterion includes a group of quality indicators. The methodological tools was developed, which was used for pedagogical diagnostics of this professional quality forming in future specialists of preschool education. The experimental study helped to identify the characteristics of qualitative measurements for primary, reproductive and creative levels of readiness of future preschool teachers’ professional training. We see the prospect of further research in the development of methodology of future specialists of preschool education preparing to creative self-realization in professional activity.El artículo está dedicado a la cuestión de los futuros especialistas de formación en educación preescolar para la autorrealización creativa en la actividad profesional. Los autores del artículo revelan el diagnóstico pedagógico de la preparación para la autorrealización creativa en la actividad profesional de los estudiantes de instituciones de educación superior. El propósito del estudio es revelar los resultados deldiagnóstico pedagógico de futuros especialistas en preparación para la educación preescolar para la autorrealización creativa en la actividad profesional. Se ha desarrollado una metodología diagnóstica y criterios de futuros especialistas de educación preescolar para la autorrealización creativa en la preparación para la actividad profesional. Los criterios de los futuros especialistas de la educación preescolar para la autorrealización creativa en la preparación para la actividad profesional son: motivadores y valiosos, actividad creativa, evaluación y reflexión. Cada criterio incluye un grupo de indicadores de calidad. Se desarrollaron las herramientas metodológicas, que se utilizaron para el diagnóstico pedagógico de esta calidad profesional formando en futuros especialistas de educación preescolar. El estudio experimental ayudó a identificar las características de las mediciones cualitativas para los niveles de preparación primaria, reproductiva y creativa de la formación profesional de los futuros maestros de preescolar. Vemos la posibilidad de una mayor investigación en el desarrollo de la metodología de futuros especialistas en educación preescolar que se preparan para la autorrealización creativa en la actividad profesional

The Readiness of Future Specialists of Preschool Education to Creative Self-Realization in Professional Activity

The article is devoted to the issue of future specialists of preschool education training to creative self-realization in professional activity. The authors of the article reveal the pedagogical diagnostics of readiness to creative self-realization in professional activity of higher educational institutions’ students. The purpose of the study is to reveal the results of pedagogical diagnostics of future specialists of preschool education readiness to creative self-realization in professional activity. A diagnostic methodology and criteria of future specialists of preschool education to creative self-realization in professional activity readiness has developed. The criteria of future specialists of preschool education to creative self-realization in professional activity readiness are: motivational and valuable, creative activity, assessment and reflective. Each criterion includes a group of quality indicators. The methodological tools was developed, which was used for pedagogical diagnostics of this professional quality forming in future specialists of preschool education. The experimental study helped to identify the characteristics of qualitative measurements for primary, reproductive and creative levels of readiness of future preschool teachers’ professional training. We see the prospect of further research in the development of methodology of future specialists of preschool education preparing to creative self-realization in professional activity

Nauczanie polskich uczniów czytania początkowego w języku angielskim: podejście tradycyjne i współczesne

Learning to read in English usually poses a challenge for early EFL learners because the language represents a deep orthography, which is manifested by the irregularities in the relation between the written and spoken form of words. Teaching learners to read amid such irregularities requires advanced linguistic knowledge and appropriate didactic solutions on part of the teachers. The research concerns in–service teachers’ knowledge of the fundamental subcomponents of early reading, their familiarity with some linguistic terms necessary in teaching early reading and use of appropriate didactic applications. The current study is quantitative and qualitative in nature; a survey was conducted among primary school, Polish EFL teachers working in and around Biała Podlaska. The research indicates that the knowledge teachers have regarding the development of early reading is considerable, however, in some cases the basic linguistic terminology, i.e. phonological awareness, seems to be misunderstood. Also, in some cases, the choice of early EFL reading instruction in early literacy does not follow the current recommendations. The results suggest that in–service, primary school, Polish EFL teachers might need additional, supplementary training in early reading development. It can also be concluded that university courses aimed at pre-service EFL teachers should devote more time and resources to early reading development in English

Nash – Disequilibrium, Random Decisions and Imbalance of Society: Is it Relevant to Ukraine?

Ukrainian society is undergoing rapid transformational changes. The authors attempted to identify the main behavioral strategies before the war as well as possible changes in the following years. Attempting to recognize the most prevalent behavior in society, the interaction and attitude of students during the exam were taken into consideration. The student group includes representatives of various regions in proportionate numbers. The research is based on the simulation of the interaction of different groups in society by means of game theory and programming. The study proposes using Schumpeter market disturbances and ‘Nash disequilibrium’ to invigorate the current ineffective system. It has been shown that pre-war Ukrainian society exhibited a very high level of collusion. The interim conclusions were tested using Axelrod’s tournament algorithms and strategies. A simulation of the cooperative equilibrium in Ukrainian society during the pre-war period was demonstrated. The study also contains important predictions about the changes in the institutional environment in the aftermath of the war in Ukraine

Infectious complication or exacerbation of granulomatosis with polyangiitis?

Granulomatosis with polyangiitis (GPA) is a primary, systemic small vessel vasculitis. The respiratory tract is typically involved in the course of the disease. Abnormalities on the chest radiograph are noted in more than 70% patients at some point during their disease history. In some clinical situations it is difficult to distinguish whether symptoms result from the underlying disease or are a symptom of infection. In these clinical situations, chest computed tomography (CT) can be very useful. We present a patient with GPA localized mainly in the respiratory tract with sudden deterioration of the general state and new abnormalities revealed in the CT of the chest

The Development of Coherent Speech in Elementary School Students in The Process of Constructive and Artistic Activity

The article examines the development of speech in elementary school students. The research objective is to determine the status of coherent speech development in 3rd-grade students in the process of constructive and artistic activity. The article defines the criteria (structural and compositional, communicative and productive, and communicative and creative), indicators, and levels of development of coherent speech in elementary school students in the process of constructive and artistic activity. Each criterion includes a group of qualitative content-disclosing indicators and characterizes the achievements of students in the intended type of activity. Based on this, the authors have developed a methodological tool that allows them to diagnose coherent speech development in 3rd-grade students in the process of constructive and artistic activity and to conduct a precise quantitative differentiation by high, sufficient, medium, and low levels of coherent speech formation with specific characteristics for qualitative measurements that open up prospects for the development of appropriate effective measures for improving the quality of training students for such activity.El artículo examina el desarrollo del habla en estudiantes de primaria. El objetivo de la investigación es determinar el estado del desarrollo coherente del habla en estudiantes de tercer grado en el proceso de actividad constructiva y artística. El artículo define los criterios (estructurales y compositivos, comunicativos y productivos, y comunicativos y creativos), indicadores y niveles de desarrollo del discurso coherente en estudiantes de primaria en el proceso de actividad constructiva y artística. Cada criterio incluye un grupo de indicadores cualitativos de divulgación de contenido y caracteriza los logros de los estudiantes en el tipo de actividad prevista. En base a esto, los autores han desarrollado una herramienta metodológica que les permite diagnosticar el desarrollo coherente del habla en estudiantes de tercer grado en el proceso de actividad constructiva y artística y llevar a cabo una diferenciación cuantitativa precisa por niveles altos, suficientes, medios y bajos de formación coherente del habla con características específicas para mediciones cualitativas que abren perspectivas para el desarrollo de medidas efectivas apropiadas para mejorar la calidad de la capacitación de los estudiantes para dicha actividad