Phenoxypropanolamine derivatives as selective inhibitors of the 20S proteasome ß1 and ß5 subunits.

New series of thiophene-containing phenoxypropanolamines were synthesized and evaluated for their potency to inhibit the three proteolytic activities of the mammalian 20S proteasome. Noticeable inhibition of both ChT-L and PA activities was obtained with three compounds: one with unsubstituted phenoxypropanolamine group (7) and the two others with a p-Cl-substituted group (4 and 9). For three other compounds (3, 8 and 10), ChT-L activity alone was significantly inhibited. In silico docking performed on the ß5 and ß1 subunits bearing the respective ChT-L and PA catalytic sites showed features common to poses associated with active compounds. These features may constitute a selectivity criterion for structure-guided inhibitor design.

New C(4)- and C(1)-derivatives of furo[3,4-c]pyridine-3-ones and related compounds: evidence for site-specific inhibition of the constitutive proteasome and its immunoisoform.

A set of 18 new C(4) and C(1) derivatives of nor-cerpegin (1,1-dimethyl furo[3,4-c]pyridine-3-one), 6 model compounds (γ- and δ-lactones) and 20 furo- or thieno[2,3-d]-pyrimidine-4-one related compounds were designed and synthesized. Each compound was assayed for inhibition of CT-L, T-L and PA proteolytic activities of 20S constitutive proteasome (c20S). Most performant compounds were also assayed on 20S immunoproteasome (i20S). Compound 10 with a benzylamino group at C(4) and dimethylated at C(1) of the furopyridine ring was the most efficient PA site-specific inhibitor of the c20S (IC50(cPA) of 600nM) without noticeable inhibition of the i20S PA site (iPA). In silico docking assays for 10 at the iPA catalytic site revealed the absence of poses normally observed for this compound and related ones at the constitutive PA site (cPA). The thieno[2,3-d]pyrimidine-4-one 40 was T-L site-specific with a mild inhibition of both c20S and i20S in vitro (IC50(cT-L) of 9.9µM and IC50(iT-L) of 6.7µM). In silico docking assays of 40 at T-L sites of c20S and i20S revealed almost identical first rank poses in the two types of sites with no possibility left for nucleophilic attack by Thr1 as observed for the fused furopyridine-3-one 10.

Learning difficulties in school children: health and education professionals' perceptions.

OBJECTIVES: to understand health and education professionals' perceptions regarding children's learning difficulties in public schools. METHODS: qualitative research, of the participatory action type, linked to Paulo Freire's Research Itinerary. Forty-five professionals participated, through interviews and a Virtual Culture Circle. The analysis was developed through careful reading, reflection and interpretation of highlighted topics. RESULTS: professionals discussed the (in)visibility of learning difficulties, strategies and resources in the educational sector and the search for solutions in the health sector. It was found that the production of complaints related to school learning is attributed predominantly as an individual problem of children or their family, exempting the educational institution from this process. FINAL CONSIDERATIONS: greater investment in professional training and development policies is urgently needed to facilitate coordination between sectors, with a view to overcoming outdated pedagogical and health models.

Culture circle in primary care: dialogues with managers on health promotion.

OBJECTIVE: To identify health promotion strategies used by managers in primary health care. METHOD: Qualitative research, of a participant action nature, which adopted the Culture Circle proposed by Paulo Freire as its methodological reference. Eleven primary health care managers from a medium-sized municipality in southern Brazil took part. RESULTS: Nine generative themes emerged, categorized into four themes that highlight the interconnection between health promotion, social determinants and primary health care. These themes highlight preventive approaches, healthy habits and underline the need for a multidisciplinary approach to health care, recognizing the complexity of the dimensions involved, the influence of social determinants, environmental and health issues. These aspects call for intersectoral policies and actions, demonstrating the viability of health promotion in line with the principles of the Unified Health System. FINAL CONSIDERATIONS: The autonomy of professionals working in primary health care services is highlighted, especially that of nurses, who play a central role in connecting and organizing health promotion actions.

C1 and N5 derivatives of cerpegin: synthesis of a new series based on structure-activity relationships to optimize their inhibitory effect on 20S proteasome.

Thirty-two new derivatives of cerpegin (1,1,5-trimethylfuro[3,4-c]pyridine-3,4-dione) were designed and synthesized in high yield by a new method, combining several C(1) and N(5) substituents. All compounds were tested for their inhibitory effect on the CT-L, T-L and PA proteolytic activities of a purified mammalian 20S proteasome. Only one molecule inhibited both CT-L and PA activities. Sixteen molecules specifically inhibited PA at the micromolar range, out of which fourteen had IC50 values around 5 µM and two had IC50 values closer to 2 µM. Except in one case, neither calpain I nor cathepsin B was inhibited. In silico docking suggests a unique mode of binding of the most efficient compounds to the ß1 catalytic site (PA activity) in relation to the chemical nature of C(1) substituents.

[The promotion of women's autonomy during family health nursing consultations]. / Promoção da autonomia da mulher na consulta de enfermagem em saúde da família.

We adopted a qualitative approach combined with the methodological framework of Paulo Freire, consisting of thematic investigation, coding and decoding, and critical unveiling, to understand whether nursing consultation promotes women's autonomy in a health center. Six Culture Circles that were each two hours long were conducted, with an average of nine participants each, between May and July 2011. The investigation revealed eight topics of importance, although two were particularly important: the need for dialogue on domestic violence and the relationship between nurses and participants during consultations. The results indicate that consultations may present a space for women to take actions that they may otherwise be fearful to take. Our results highlight the need for multidisciplinary training of nurses with regard to strategies for promotion and intensification of their practices in the Unified Health System.

Remote teaching during the COVID-19 pandemic: repercussions from professors' perspective.

OBJECTIVES: to understand the repercussions of teaching work in remote teaching during the COVID-19 pandemic in Higher Education Institutions in northern Santa Catarina. METHODS: a qualitative participatory action research, based on Paulo Freire's theoretical-methodological precepts. Seventeen health professors participated in two Virtual Culture Circles held in the first half of 2021. RESULTS: six generating themes emerged for discussion, which aroused in participants' feelings and perspectives regarding the remote teaching process in the pandemic context, with an emphasis on the connectivity theme, which generated dialogue through reports of personal experiences. FINAL CONSIDERATIONS: the pandemic has had repercussions in sectors such as health and education. Professors talked about their experience in creating, recreating and adapting to remote teaching and the challenges facing the teaching-learning process, listing the worsening of mental health and the need to learn new digital technologies.

A new series of N5 derivatives of the 1,1,5-trimethyl furo[3,4-c]pyridine-3,4-dione (cerpegin) selectively inhibits the post-acid activity of mammalian 20S proteasomes.

A large set of N(5)-derivatives of cerpegin (1,1,5-trimethyl furo[3,4-c]pyridine-3,4-dione) was designed and synthesized in high yields by a simple and handy method using various primary amines for a pyridine cycle synthesis. The effects of 29 derivatives on the three types of catalytic sites of purified mammalian 20S proteasomes (CT-L, T-L and PA) were measured. Most of the new compounds specifically inhibited the PA activity, in the micromolar range. Docking experiments support these results. Moreover, neither calpain I nor cathepsin B were inhibited.

Reflections of the social determinants of health on school children's learning.

OBJECTIVE: understanding the repercussions of the social determinants of health on school children's learning, linked to the public-school network, from the point of view of health and education professionals. METHOD: qualitative study, participant-action type, articulated to Freire's Research Itinerary, through three moments: Thematic Investigation; Coding and Decoding; Critical Unveiling. The participants were 27 health professionals and 18 education professionals, working in four municipalities of Santa Catarina. Individual interviews and a Culture Circle took place between November 2020 and March 2021. The analysis was developed in the discussions in the Culture Circle, with reflection on the themes. RESULTS: unfavorable living conditions, unhealthy habits, and weak social relationships tend to negatively influence children's school learning. There is a need for the implementation of actions involving the health and education sectors, such as the Health at School Program. CONCLUSION: the articulated action of health and education professionals on social determinants is the way to promote health and children's school performance, in order to minimize the effects of existing inequities.

Circle dance: integrative and complementary practice in the daily health promotion for older adults.

OBJECTIVES: to understand circle dance as an integrative and complementary practice for health promotion in older adults' daily lives. METHODS: an interpretive, qualitative study, based on Michel Maffesoli's Comprehensive Sociology of Everyday Life. There were 20 participants, 17 older adults and three focalizers in circles held in Basic Health Units in a municipality in southern Brazil. Data were collected through interviews and observation, between September 2016 and March 2017, and analyzed through preliminary analysis, ordering, key links, coding and categorization. RESULTS: three categories emerged that express the daily life of circle dance with older adults: circles that spin; challenges for new circles to spin; entering, being and staying in the circle. FINAL CONSIDERATIONS: circle dance provided older adults with a feeling of belonging to a group, combined with pleasure and well-being, contributing to promotion of older adults' health.

Nurse's actions in the interface with expanded services of Family Health and Primary Care Center. / Ações do enfermeiro na interface com os núcleos ampliados de Saúde da Família e Atenção Básica.

OBJECTIVE: To understand the actions of nurses from the perspective of the interface of performing with the Expanded Services of Family Health and Primary Care Center. METHOD: Qualitative participatory research based on the Freirean Itinerary, from the following steps: thematic research; encoding and decoding; and critical unveiling. The information was obtained through four Culture Circles, with nurses from Family Health teams, between April and June 2018. RESULTS: A total of nine nurses participated in the study. Among the generative topics emerged, there is the "relationship between generalist teams and the health center: nurses as a reference and interprofessional bond". Nurses perceive themselves in this way because of generalist and managerial training. Shared activities as groups are among the practices developed collectively and that strengthen interprofessional work. CONCLUSION: By provoking reflections on autonomy and the work process in collaborative performance with the Centers, the study expanded the perception about the actions developed by nurses in the interaction with the multiprofessional team. It is suggested to carry out other studies on interprofessionality in the relationship between nursing and the extended services through the perspective of the Center professionals.

[Health promotion and primary care for people with chronic non-transmissible diseases]. / Promoção da saúde e atenção primária no cuidado às pessoas com doença crônica não transmissível.

OBJECTIVE: Understand the health promotion practices developed by primary health care nurses in a southern county of Brazil, in the care of people with chronic non-communicable diseases. METHOD: Qualitactive research, developed by multiple speeches, in twenty three health centers of a southern county of Brazil. RESULTS: According to speeches, the health promotion practices developed by nurses refer to two main fields, of the five action fields proposed by the Ottawa Letter: reorientation of the health system and developing personal abilities. It appeared as a speech, related to the central idea about the limits to developing fields of the Ottawa letter. CONCLUSIONS: Besides the efforts spent to develop health promotion practices, these appear in some moments in an amplified way, thinking in a new logic to Health promotion and in other situations it shows itself in a more restrictive way, returning to a more traditional practice.

Novel fluorinated pseudopeptides as proteasome inhibitors.

We have designed novel small inhibitors of rabbit 20S proteasome using a trifluoromethyl-beta-hydrazino acid scaffold. Structural variations influenced their inhibition of the three types of active sites. Proteasome inhibition at the micromolar level was selective, calpain I and cathepsin B were not inhibited.

Social determinants of a Quilombola Community and its interface with Health Promotion.

OBJECTIVE: Understanding the relationship of social determinants in the Health Promotion of quilombola women. METHOD: This was a participatory study developed through the Research Itinerary of Paulo Freire, which comprises three stages: thematic investigation, codification and decoding, and critical unveiling. These stages were developed in Culture Circles from April to June 2016. Twenty themes were investigated, coded and decoded into eight themes, revealing the theme of women and their relationship with the Social Determinants. RESULTS: Ten women from a quilombola community in Santa Catarina participated. The Health Promotion of this population and its interface with Social Determinants were understood. Health, religiosity, racial issues, social and community networks emerged as potentializing community empowerment and solidification. CONCLUSION: An accentuated correlation of racial issues and fragility combined with health care, education and information, and above all the distancing of vulnerable communities from comprehensive and equitable health was observed, highlighting the imminent need to strengthen Health Promotion strategies.

Management of cardiovascular health in acute leukemia: a national survey.

Cardiovascular (CV) disease is a common comorbidity in acute leukemia (AL) patients and can be worsened by the use of anthracyclines. Interruptions and underutilization of CV medications during AL treatments may negatively impact the CV health of these patients. A 30-question electronic survey was distributed to Canadian hematologists who treat adults with AL to determine the frequency, timing and rationale for interruptions in statins, antiplatelets and angiotensin antagonists in patients undergoing intensive chemotherapy. Strategies for mitigating anthracycline cardiotoxicity, methods of establishing baseline CV risk and utilization of clinical pharmacists were also assessed. Results indicate that it is common for AL patients undergoing intensive chemotherapy to require CV medication interruptions. This highlights the need for collaboration between hematology and cardiology healthcare teams and utilization of multidisciplinary healthcare professionals to improve CV care during AL.

Culture circle in primary care: dialogues with managers on health promotion / Círculo de cultura en atención primaria: diálogos con directivos sobre promoción de la salud / Círculo de cultura na atenção primária: diálogos com gestores sobre promoção da saúde

ABSTRACT Objective: To identify health promotion strategies used by managers in primary health care. Method: Qualitative research, of a participant action nature, which adopted the Culture Circle proposed by Paulo Freire as its methodological reference. Eleven primary health care managers from a medium-sized municipality in southern Brazil took part. Results: Nine generative themes emerged, categorized into four themes that highlight the interconnection between health promotion, social determinants and primary health care. These themes highlight preventive approaches, healthy habits and underline the need for a multidisciplinary approach to health care, recognizing the complexity of the dimensions involved, the influence of social determinants, environmental and health issues. These aspects call for intersectoral policies and actions, demonstrating the viability of health promotion in line with the principles of the Unified Health System. Final considerations: The autonomy of professionals working in primary health care services is highlighted, especially that of nurses, who play a central role in connecting and organizing health promotion actions.

RESUMEN Objetivo: Identificar las estrategias de promoción de la salud utilizadas por gestores en la atención primaria de salud. Método: Investigación cualitativa, de tipo acción participante, que adoptó como referencia metodológica el Círculo de Cultura propuesto por Paulo Freire. Participaron 11 gestores de atención primaria de salud de un municipio de tamaño medio del sur de Brasil. Resultados: Surgieron nueve temas generativos, categorizados en cuatro temáticas que destacan la interconexión entre la promoción de la salud, los determinantes sociales y la atención primaria de salud. Estos temas destacan los enfoques preventivos, los hábitos saludables y subrayan la necesidad de un enfoque multidisciplinar de la atención sanitaria, reconociendo la complejidad de las dimensiones implicadas, la influencia de los determinantes sociales y las cuestiones medioambientales y sanitarias. Estos aspectos exigen políticas y acciones intersectoriales, demostrando la viabilidad de la promoción de la salud en consonancia con los principios del Sistema Único de Salud. Consideraciones finales: Se destaca la autonomía de los profesionales que actúan en los servicios de atención primaria de salud, especialmente la de las enfermeras, que desempeñan un papel central en la conectividad y organización de las acciones de promoción de la salud.

RESUMO Objetivo: Identificar estratégias de promoção da saúde utilizadas por gestores na atenção primária à saúde. Método: Pesquisa qualitativa, de natureza ação participante, que adotou como referencial metodológico o Círculo de Cultura proposto por Paulo Freire. Participaram 11 gestores da atenção primária à saúde de um município de médio porte do sul do Brasil. Resultados: Surgiram nove temas geradores categorizados em quatro temáticas que evidenciam a interconexão entre promoção da saúde, determinantes sociais e atenção primária à saúde. Essas temáticas destacam abordagens preventivas, hábitos saudáveis e sublinham a necessidade de uma abordagem multidisciplinar na atenção à saúde, reconhecendo a complexidade das dimensões envolvidas, a influência dos determinantes sociais, questões ambientais e sanitárias. Tais aspectos demandam políticas e ações intersetoriais, evidenciando a viabilidade da promoção da saúde alinhada aos princípios do Sistema Único de Saúde. Considerações Finais: Destaca-se a autonomia dos profissionais que atuam em serviços de atenção primária à saúde, especialmente a do enfermeiro, que desempenha um papel central na conectividade e ordenação das ações de promoção da saúde.

Learning difficulties in school children: health and education professionals' perceptions / Dificultades de aprendizaje en escolares: percepciones de los profesionales de la salud y la educación / Dificuldade de aprendizagem de crianças escolares: percepções dos profissionais da saúde e da educação

ABSTRACT Objectives: to understand health and education professionals' perceptions regarding children's learning difficulties in public schools. Methods: qualitative research, of the participatory action type, linked to Paulo Freire's Research Itinerary. Forty-five professionals participated, through interviews and a Virtual Culture Circle. The analysis was developed through careful reading, reflection and interpretation of highlighted topics. Results: professionals discussed the (in)visibility of learning difficulties, strategies and resources in the educational sector and the search for solutions in the health sector. It was found that the production of complaints related to school learning is attributed predominantly as an individual problem of children or their family, exempting the educational institution from this process. Final Considerations: greater investment in professional training and development policies is urgently needed to facilitate coordination between sectors, with a view to overcoming outdated pedagogical and health models.

RESUMEN Objetivos: comprender las percepciones de los profesionales de la salud y la educación sobre las dificultades de aprendizaje de los niños en las escuelas públicas. Métodos: investigación cualitativa, del tipo acción participativa, vinculada al Itinerario de Investigación de Paulo Freire. Participaron 45 profesionales, a través de entrevistas y un Círculo Virtual de Cultura. El análisis se desarrolló a través de una atenta lectura, reflexión e interpretación de los temas destacados. Resultados: los profesionales discutieron la (in)visibilidad de las dificultades de aprendizaje, las estrategias y los recursos en el sector educativo y la búsqueda de soluciones en el sector salud. Se encontró que la producción de quejas relacionadas con el aprendizaje escolar se atribuye predominantemente como un problema individual del niño o de su familia, eximiendo a la institución educativa de este proceso. Consideraciones Finales: urge una mayor inversión en políticas de formación y desarrollo profesional para facilitar la coordinación entre sectores, con miras a superar modelos pedagógicos y sanitarios obsoletos.

RESUMO Objetivos: conhecer as percepções dos profissionais da saúde e da educação acerca da dificuldade de aprendizagem de crianças da rede pública de ensino. Métodos: pesquisa qualitativa, do tipo ação participante, articulada ao Itinerário de Pesquisa de Paulo Freire. Participaram 45 profissionais, por meio de entrevistas e um Círculo de Cultura Virtual. A análise desenvolveu-se na leitura cuidadosa, reflexão e interpretação dos temas destacados. Resultados: os profissionais dialogaram sobre a (in)visibilidade da dificuldade de aprendizagem, as estratégias e os recursos do setor educacional e a busca por resolutividade no setor saúde. Verificou-se que a produção das queixas relacionadas à aprendizagem escolar está atribuída predominantemente como problema individual da criança ou de sua família, isentando a instituição educacional desse processo. Considerações Finais: é premente maior investimento em políticas de formação e aperfeiçoamento dos profissionais para propiciar a articulação entre os setores, com vistas a superar modelos pedagógicos e de saúde ultrapassados.

Promoção da saúde à pessoa com diabetes: percepções dos profissionais da atenção primária à saúde / Health promotion for people with diabetes: perceptions of primary health care professionals / Promoción de la salud para personas con diabetes: percepciones de los profesionales de atención primaria de salud

Objetivo: identificar a percepção dos profissionais de saúde que atuam na atenção primária sobre a promoção da saúde às pessoas com Diabetes. Método: estudo qualitativo, do tipo pesquisa ação, por meio do Itinerário de Pesquisa de Paulo Freire, que compreende três etapas: investigação temática, codificação e descodificação e desvelamento crítico. Realizou-se um círculo de cultura em setembro de 2021 com seis profissionais de saúde de uma Unidade Básica de uma cidade do sul do Brasil. Resultados: os profissionais identificaram que a saúde não é somente ausência da doença, mas envolve os determinantes sociais na vida da pessoa. Relacionam a promoção da saúde com as condições socioeconômicas, estilo de vida e equilíbrio entre ambos. Considerações finais: os profissionais ao identificarem o cuidado com base nos determinantes sociais e a promoção da saúde vislumbraram a construção de um protocolo individual de atendimento com melhoria da qualidade de vida das pessoas com diabetes(AU)

Objective: to identify the perception of health professionals working in primary care about health promotion for people with diabetes. Method: qualitative study, of the action research type, through Paulo Freire's Research Itinerary, which comprises three stages: thematic investigation, codification and decoding and critical unveiling. A culture circle was held in September 2021 with six health professionals from a Basic Unit in a city in southern Brazil. Results: professionals identified that health is not just the absence of disease, but involves social determinants in a person's life. They relate health promotion with socioeconomic conditions, lifestyle and balance between both. Final considerations: when professionals identified care based on social determinants and health promotion, they envisioned building an individual care protocol with improved quality of life for people with diabetes(AU)

Objetivo: identificar la percepción de los profesionales de la salud que trabajan en la atención primaria sobre la promoción de la salud de los pacientes con diabetes. Método: estudio cualitativo, del tipo investigación acción, a través del Itinerario de Investigación de Paulo Freire, que comprende tres etapas: investigación temática, codificación y decodificación y develamiento crítico. En septiembre de 2021, se realizó un círculo de cultura con seis profesionales de la salud de una Unidad Básica de una ciudad del sur de Brasil. Resultados: los profesionales han identificado que la salud no es sólo la ausencia de enfermedad, sino que involucra determinantes sociales en la vida de una persona. Relacionan la promoción de la salud con las condiciones socioeconómicas, el estilo de vida y el equilibrio entre ambos. Consideraciones finales: cuando los profesionales identificaron la atención basada en los determinantes sociales y la promoción de la salud, vislumbraron la construcción de un protocolo de atención individual con mejora de la calidad de vida de las personas con diabetes(AU)

Promoting the autonomy of rural older adults in active aging.

OBJECTIVE: to understand how the rural older adults promote their autonomy in active aging. METHOD: qualitative research through the Paulo Freire's research itinerary, consisting of three steps: area of research; encoding and decoding; and critical unveiling. Seventeen older adults living in the rural area of a municipality in Southern Brazil participated in the research. Six culture circles were conducted from July to December 2016. RESULTS: the investigation revealed two generating themes: joint pain and participation in groups. The understanding of autonomy promotion for the active aging of older adults is focused on the physical capacity and independence of activities of daily living. FINAL CONSIDERATIONS: the culture circles have promoted reflection moments for the participants, especially about the advantages and difficulties related to the practice of autonomy in the exercise of citizenship for active aging in the rural area.

Nursing care practices for people with Chronic Noncommunicable Diseases.

OBJECTIVE: To understand care practices for people with Chronic Noncommunicable Disease, developed by Primary Health Care nurses in a municipality in southern Brazil. METHOD: Qualitative study, developed through the Discourse of the Collective Subject. Twenty-three nurses from the Family Health Strategy participated. Data were collected through semi-structured interviews and analyzed by the health promotion framework. RESULTS: Nurses care practices for people with chronic disease present themselves through the home visit, individual care and collective care. These, eventually, have an extended character, advocating the promotion of health, at other times it is restrictive, returning to be a traditional and biologicalist practice. FINAL CONSIDERATIONS: The nurse acts in a diversified way in this field, being present in the lives of people with chronic diseases. However, it is necessary to move forward, especially in the search for the constant and continuous development of an extended and welcoming care practice.