Unveiling new myrsinoic acids and AChE ligands from Myrsine guianensis (Aubl.) Kuntze.

Molecular dereplication and drug-like discovery are important tools for exploring the chemical profile of metabolites in a complex mixture. In order to establish a workflow for discovering novel acetylcholinesterase (AChE) ligands, we performed the chemical study of Myrsine guianensis (Aubl.) Kuntze (Primulaceae). To carry out the bioprospection, nine extracts were obtained from different parts of the plant. Through the dereplication approaches, seventeen metabolites were annotated. In order to confirm the putative inferences, a HPLC preparative method was developed to isolate three known myrsinoic acids, A(1), B(2) and C(3). Along with, we are reporting the obtention of two new congeners, G(5) and H(6), which their structures were elucidated by NMR and HRMS data. Besides that, two extracts were submitted to affinity assays to accelerate the discovery of AChE ligands. Desorbates were analyzed through LC-HRMS for calculating the affinity ratio (AR). Thus, (1) presented AR = 4.59, therefore was considered a potential ligand.

Ligand fishing approach to explore Amaryllidaceae alkaloids as potential antiviral candidates targeting SARS-CoV-2 Nsp4.

Ligand fishing, also described as affinity-based assay, represents a convenient and efficient approach to separate potential ligands from complex matrixes or chemical libraries. This approach contributes to the identification of lead compounds that can bind to a specific target. In the context of COVID-19, the search for novel therapeutic agents is crucial. Small molecule-based antiviral drugs, such as Amaryllidaceae alkaloids, have been described as potential candidates because they can inhibit RNA viruses. Among various SARS-CoV-2 proteins, Nsp3, Nsp4, and Nsp6 play a crucial role in the pathogenicity of the virus and are attractive targets for developing COVID-19 treatments. These proteins are responsible for the replication/transcription complex (RTC) within double-membrane vesicles (DMVs), and their inhibition disrupts the virus's infectious cycle. Herein, we have successfully expressed and immobilized the SARS-CoV-2 Nsp4 protein on magnetic beads (Nsp4-MBs) and employed a ligand fishing assay to screen a collection of ten Amaryllidaceae-based alkaloids and applied to Hippeastrum aulicum extract. Remarkably, four out of ten alkaloids, namely 2-α-7-dimethoxyhomolycorine (6), haemanthamine (5), albomaculine (8), and tazettine (9), exhibited selective affinities for Nsp4. Albomaculine (8) and haemanthamine (5) were also identified from extract by the affinity assay. These findings highlight the potential of these alkaloids as model compounds for future drug discovery studies aimed at developing therapeutic interventions against SARS-CoV-2 infections.

A experiência estética como facilitadora de grupos na saúde mental / The aesthetic experience as a facilitator of mental health groups

A experiência estética pode ser compreendida como uma vivência que emerge na intencionalidade homem e mundo por meio de expressões artísticas e sensíveis, recebidas de forma mobilizadoras à percepção. O objetivo deste artigo foi compreender como essa experiência foi significada por participantes do Grupo Comunitário de Saúde Mental, que tem como premissa a atenção à experiência cotidiana, entre elas, a experiência vivida com elementos estéticos como filmes, músicas, entre outros. O corpus formou-se pela observação participante por dois anos e seis meses e por nove entrevistas abertas, baseado no referencial teórico metodológico da Fenomenologia. A experiência estética proporcionou uma forma de religar a pessoa e o mundo em uma unicidade criativa, a partir da exploração do potencial simbólico de elementos disponíveis na cultura, bem como favoreceu a constituição de encontros, de reciprocidade e de surpresas na relação com o outro, fortalecendo a dimensão comunitária da atividade.

A Comprehensive 2D-LC/MS Online Platform for Screening of Acetylcholinesterase Inhibitors.

The continuous interest in discovering new bioactive molecules derived from natural products (NP) has stimulated the development of improved screening assays to help overcome challenges in NP-based drug discovery. Here, we describe a unique platform for the online screening of acetylcholinesterase inhibitors without the need for pre-treating the sample. In the current study, we have demonstrated the ability to combine reversed-phase separation with a capillary immobilized enzyme reactor (cIMER) in two-dimensional liquid chromatography system coupled with mass spectrometry detection. We systematically investigated the effects of method parameters that are of practical significance and are known to affect the enzyme assay and interfere in the analysis such as: bioreactor dimensions, loop sizes, amount of immobilized enzyme, second dimension flow rates, reaction time, substrate concentration, presence of organic modifier, limit of detection and signal suppression. The performance of this new platform was evaluated using a mixture containing three known AChE inhibitors (tacrine, galanthamine and donepezil) and an ethanolic extract obtained from the dry bulbs of Hippeastrum calyptratum (Amaryllidaceae) was investigated to provide a proof of concept of the applicability of the platform for the analysis of complex mixtures such as those derived from NPs.

Psychological recovery after critical illness and stay in hospital ICU / Recuperação psicológica após adoecimento grave e internação em UTI / Recuperación psicológica después de una enfermedad grave y admisión en la UCI

The effects of critical illness and hospitalization in intensive care units (ICU) have been associated with the presence of negative psychological consequences. This study explores the experiences of sick people who were admitted to an ICU, seeking to know its repercussions on the self. In-depth qualitative interviews and participant observations were carried out with two people since their ICU admission until at least six months after discharge from the unit. Data was analyzed following an adaptation of the clinical qualitative method within a longitudinal frame and interpreted with Winnicott's psychoanalytic perspective. This research managed to describe participants' lived experiences and the ways they affected their psychic organization. To the interviewed, these experiences configured threshold situations which promoted a process of psychic disintegration. Psychological recovery, then, depends on the articulation of lived experiences, and is supported by facilitating intersubjective relationships that promote the expression of personal potentialities.(AU)

Os efeitos do adoecimento crítico e da hospitalização em Unidade de Terapia Intensiva (UTI) têm sido associados a consequências psicológicas negativas. Este estudo investiga as experiências de pessoas adoecidas que foram internadas em UTI, buscando compreender suas repercussões no self. Foram realizadas entrevistas qualitativas em profundidade e observações participantes com duas pessoas, desde a admissão na UTI até, no mínimo, seis meses após a alta. Os dados foram analisados seguindo uma adaptação do método clínico qualitativo, em um enquadre longitudinal, e interpretados a partir da perspectiva psicoanalítica winnicottiana. A pesquisa descreveu as experiências vividas pelos participantes e a forma como elas afetaram sua organização psíquica. Para os entrevistados, essas experiências se configuraram como situações limite, que estimularam um processo de desintegração psíquica. A recuperação psicológica, por sua vez, depende da articulação das experiências vividas, e é sustentada por relações intersubjetivas facilitadoras que promovem a expressão de potencialidades pessoais.(AU)

Los efectos de una enfermad grave y de la hospitalización en Unidades de Cuidados Intensivos (UCI) se asocian a consecuencias psicológicas negativas. Este estudio abordó las experiencias de personas enfermas hospitalizadas en UCI, con el fin de comprender sus repercusiones en el self. Se realizaron entrevistas cualitativas a profundidad y observaciones participantes con dos personas, desde la admisión en la UCI hasta, por lo menos, seis meses después de haber dado el alta el paciente. Los datos se analizaron de acuerdo con una adaptación del método clínico cualitativo, en un marco longitudinal, y para su interpretación se aplicó la perspectiva psicoanalítica winnicottiana. La investigación describió las experiencias de los participantes y la forma como estas han afectado sus organizaciones psíquicas. Según los entrevistados, las experiencias se configuraron como situaciones límite, las cuales han promovido un proceso de desintegración psíquica. La recuperación psicológica dependió de la articulación de las experiencias vividas y estuvo sostenida por relaciones intersubjetivas facilitadoras, las cuales promovieron la expresión de potencialidades personales.(AU)

Co-Immobilized Capillary Enzyme Reactor Based on Beta-Secretase1 and Acetylcholinesterase: A Model for Dual-Ligand Screening.

We have developed a dual enzymatic system assay involving liquid chromatography-mass spectrometry (LC-MS) to screen AChE and BACE1 ligands. A fused silica capillary (30 cm × 0.1 mm i.d. × 0.362 mm e.d.) was used as solid support. The co-immobilization procedure encompassed two steps and random immobilization. The resulting huAChE+BACE1-ICER/MS was characterized by using acetylcholine (ACh) and JMV2236 as substrates. The best conditions for the dual enzymatic system assay were evaluated and compared to the conditions of the individual enzymatic system assays. Analysis was performed in series for each enzyme. The kinetic parameters (KMapp) and inhibition assays were evaluated. To validate the system, galantamine and a ß-secretase inhibitor were employed as standard inhibitors, which confirmed that the developed screening assay was able to identify reference ligands and to provide quantitative parameters. The combination of these two enzymes in a single on-line system allowed possible multi-target inhibitors to be screened and identified. The innovative huAChE+BACE1-ICER/MS dual enzymatic system reported herein proved to be a reliable tool to identify and to characterize hit ligands for AChE and BACE1 in an enzymatic competitive environment. This innovative system assay involved lower costs; measured the product from enzymatic hydrolysis directly by MS; enabled immediate recovery of the enzymatic activity; showed specificity, selectivity, and sensitivity; and mimicked the cellular process.

Grupo comunitário de saúde mental: relações estabelecidas por participantes regulares de longo prazo / Mental health community group: relationships established by long-term regular participants / Grupo comunitario de salud mental: relaciones establecidas por los participantes regulares de largo plazo

RESUMO O Grupo Comunitário de Saúde Mental (GCSM) é um dispositivo de promoção da saúde mental cuja proposta de cuidado se fundamenta na atenção às experiências cotidianas. O objetivo deste artigo é compreender as relações estabelecidas por participantes regulares de longo prazo com o GCSM, ou seja, pessoas que participam há no mínimo dois anos do GCSM, de forma voluntária e ativa. Trata-se de um recorte de uma pesquisa qualitativa, realizada através de entrevista aberta e observação participante, com uso do método de análise temática. Foram entrevistados sete participantes, ex-usuários de serviços de saúde mental. A análise aponta vinculação dos participantes ao Grupo, compreendida segundo três principais temas: relações afetivas (sentimentos de valorização, gratidão e apreço pelo Grupo); relações comunitárias (relações pautadas pela empatia e movimento de solidariedade); e relações de pertencimento (processo gradual de vinculação ao Grupo, percepção de lugar de pertença). O estudo das relações estabelecidas com o GCSM contribuiu para melhor compreensão do protagonismo de pessoas em sofrimento mental, além de auxiliar a problematizar o conceito de adesão às intervenções de dispositivos de saúde mental.

ABSTRACT The Mental Health Community Group (MHCG) is a mental health promotion strategy whose care proposal is based on attention to daily experiences. The purpose of this paper is to understand the relationships established by long-term regular participants with MHCG, which means people who have been participating in the MHCG for at least two years, voluntarily and actively. This is a qualitative research, conducted through open interviews and participant observation, using the thematic analysis method. Seven participants were interviewed, who were users of mental health services. The analysis points to the participants' bond with the Group, which can be understood by three main themes: affective relationships (feelings of gratitude and appreciation for the Group); community relationships (relations based on empathy and solidarity); and belonging relationships (gradual Group connection process, perception of place of belonging). The study of the relations established with the MHCG contributed to a better understanding of the protagonism of people in mental distress, besides helping to problematize the concept of adherence to interventions of mental health strategies.

RESUMEN El Grupo Comunitario de Salud Mental (GCSM) es un dispositivo de promoción de la salud mental cuya propuesta se basa en la atención de las experiencias cotidianas. El objetivo de este artículo es comprender las relaciones establecidas por los participantes regulares a largo plazo con el GCSM, es decir, las personas que han estado participando en el GCSM durante al menos dos años, de forma voluntaria y activa. Se trata de un recorte de una investigación cualitativa, realizada mediante entrevistas abiertas y observación participante, utilizando el método de análisis temático. Fueron entrevistados siete participantes, ex usuarios del servicio de salud mental. El análisis apunta al vinculo de los participantes al Grupo, comprendido por tres temas principales: relaciones afectivas (sentimientos de valorización, gratitud y aprecio por el Grupo); relaciones comunitarias (basadas en empatia y solidaridad); y relaciones de pertenencia (proceso gradual de vinculación al grupo, percepción del lugar de pertenencia). El estudio de las relaciones establecidas con el GCSM contribuyó a una mejor comprensión del protagonismo de personas con sufrimiento mental, además de ayudar a problematizar el concepto de adhesión a las intervenciones de salud mental.

Ligand screening assay for the enzyme kallikrein immobilized on NHS-activated Sepharose.

Human tissue kallikreins (KLKs) are serine proteases involved in various physiological and pathological conditions, including cancer and neurological disorders. These enzymes constitute attractive drug targets, which has stimulated the search for new KLK inhibitors. In this study, we have covalently immobilized porcine pancreas KLK on an NHS-activated Sepharose matrix, to obtain KLK-Sepharose-NHS. The immobilized enzyme showed high recovered activity and maintained the ability of free KLK to recognize the synthetic substrate Z-Phe-Arg-AMC (KMapp = 10.3 ±â€¯0.9 µM). As proof of concept, we used leupeptin as a reference inhibitor to perform inhibition studies for KLK-Sepharose-NHS and to determine the half-maximal inhibitory concentration (IC50 = 0.13 ±â€¯0.01 µM), the inhibition constant (Ki = 0.06 µM), and the leupeptin inhibition mechanism. We evaluated several complex matrixes (plant crude extract) by the same bioassay, to demonstrate their applicability. The species Solanum lycocarpum, Stryphnodendron adstringens, and Psychotria carthagenensis gave the best results. KLK-Sepharose-NHS was fully active after six consecutive reaction cycles and retained about 60 % of its initial activity after being used for at least five months, so the bioassay developed herein is a promising strategy to screen and to identify KLK ligands.

O Conceito de Formação nas Propostas Curriculares da Psicologia brasileira de 1932 e 1962 / The Concept of Formation in the Curriculum Proposals of Brazilian Psychology of 1932 and 1962

O presente estudo objetiva compreender a ideia de formação que perpassa as primeiras propostas curriculares para o ensino da Psicologia no Brasil. Para o alcance deste objetivo foi utilizada abordagem descritiva e analítica da história da Psicologia científica, a partir do estudo de duas fontes principais, sendo elas o currículo de 1932 proposto por Waclaw Radecki e o currículo mínimo de 1962 reconhecido pelo Estado brasileiro, além de fontes complementares que versam sobre o tema. Foram identificadas duas categorias que circularam as proposições curriculares do ensino em Psicologia no Brasil, a saber: formação do psicólogo generalista e do especialista, sendo prevalente esta última. Concluímos que as propostas formativas que visaram alcançar o perfil do graduado em Psicologia no Brasil, sobretudo em sua gênese, revelam muito mais uma reação às questões político-sociais e culturais da época do que a construção de um sentido próprio para a formação do psicólogo brasileiro.

This study aims to understand the idea of education that permeates the first curricular proposals for the teaching of Psychology in Brazil. To achieve this objective, we used the descriptive and analytical approach of the history of scientific Psychology, from the study of two main sources, namely the 1932 curriculum proposed by Waclaw Radecki and the 1962 minimum curriculum recognized by the Brazilian State, in addition to complementary sources that deal with the subject. Two categories were identified that circulated as curricular propositions for teaching Psychology in Brazil, namely: education of the generalist and specialist psychologist, the latter being prevalent. We conclude that the educational proposals that aimed to reach the profile of Psychology graduates in Brazil, especially in their genesis, reveal much more a reaction to the political, social and cultural issues of the time than the construction of a proper meaning for the education of the Brazilian psychologist.

Coordenação grupal em uma modalidade de cuidado: grupo comunitário de saúde mental / Coordinación grupal en una modalidad de cuidado: grupo comunitario de salud mental / Group coordination in a mental health care intervention: community mental health group

RESUMO. O Grupo Comunitário de Saúde Mental (GCSM) configura um programa de cuidado e de promoção de saúde mental, aberto à comunidade e alinhado aos princípios da Reforma Psiquiátrica, desenvolvido ao longo de mais de 23 anos, mediante a prática, a observação sistemática e a investigação científica. O objetivo deste estudo foi compreender o papel do coordenador nesta modalidade. O corpus da pesquisa foi constituído a partir de seis sessões grupais áudio gravadas e transcritas na íntegra. Foi delineado um percurso original de análise, em que todas as intervenções do coordenador foram descritas, analisadas e contextualizadas em relação ao momento e desenvolvimento da sessão grupal. Foram identificados eixos comuns às intervenções, que as caracterizam: 'O enquadre no Grupo Comunitário de Saúde Mental'; 'O olhar para o gesto humano nas contribuições'; e 'A participação pessoal do coordenador'. A partir destes, observou-se que a forma de coordenar o GCSM guarda relação com a proposta da atividade e sua fundamentação teórica, filosófica e empírica, inspirada pela fenomenologia clássica. O enquadre, as intervenções e o posicionamento do coordenador favoreceram a constituição de um espaço de cuidado intersubjetivo, em perspectiva de horizontalidade, a partir da tarefa de reconhecer experiências cotidianas significativas ao percurso de amadurecimento da pessoa humana. Nesse sentido, este esta pesquisa aponta para a relevância do estudo aprofundado de aspectos das práticas grupais, como a coordenação, como forma de melhor descrevê-las e compreendê-las.

RESUMEN. El Grupo Comunitario de Salud Mental (GCSM) es un programa de promoción de salud mental, vuelto a la comunidad y alineado a principios de la Reforma Psiquiátrica, desarrollado a lo largo de más de 23 años, por intermedio de la práctica, la observación sistemática y la investigación científica. El objetivo de este estudio fue comprender el papel del coordinador de grupo en esta modalidad. El corpus de la investigación fue conformado a partir de seis sesiones grupales audio grabadas y transcritas. Se ha delineado una ruta original de análisis, en el que todas las intervenciones del coordinador fueron descritas, analizadas y contextualizadas en relación al momento y desarrollo de la sesión grupal. Se identificaron ejes comunes a las intervenciones, que las caracterizan: 'El encuadre en el Grupo Comunitario de Salud Mental'; 'La mirada hacia el gesto humano en las contribuciones'; 'La participación personal del coordinador'. Se observó que la forma de coordinar el GCSM se relaciona con la propuesta de la actividad y su fundamentación teórica, filosófica y empírica, inspirada en la fenomenología clásica. El encuadre, las intervenciones y el posicionamiento del coordinador estimularon la constitución de un espacio de cuidado intersubjetivo, en perspectiva de horizontalidad, a partir de la tarea de reconocer experiencias cotidianas significativas al recorrido de maduración de la persona humana. En este sentido, esta investigación apunta a la relevancia del estudio de aspectos de las prácticas grupales, como la coordinación, como forma de describirlas y comprenderlas.

ABSTRACT. The Community Mental Health Group (CMHG) is a mental health care promotion program, open to the community and inspired by the goals of Psychiatric Reform. The group has been developed over more than 23 years, through its practice, systematic observation and research. This study aimed to understand the role of the group coordinator within this group modality. The corpus of the research was constituted from six audio-recorded group sessions and transcribed in full. An original analysis was outlined in which all the coordinator's interventions were described, analysed and contextualized concerning the moment and development of the group session. Common axes have been identified, which characterize the interventions: 'The framework in the Community Mental Health Group', 'The look at the human gesture in the contributions', and 'Coordinator's personal participation'. It was observed that the CMGH's coordination is related to the proposal of the activity and its theoretical, philosophical and empirical foundation, inspired by Classical Phenomenology. The framework, interventions and coordinator's participation appeared to foster the creation of an intersubjective care space, from a horizontal perspective, based on the task of recognizing significant daily experiences in the human being's maturing path. In this sense, this research highlights the relevance of the in-depth study of group practices' aspects, such as group coordination, as a way of better describing and understanding them.

Solid-Supported Proteins in the Liquid Chromatography Domain to Probe Ligand-Target Interactions.

Ligand-target interactions play a central role in drug discovery processes because these interactions are crucial in biological systems. Small molecules-proteins interactions can regulate and modulate protein function and activity through conformational changes. Therefore, bioanalytical tools to screen new ligands have focused mainly on probing ligand-target interactions. These interactions have been evaluated by using solid-supported proteins, which provide advantages like increased protein stability and easier protein extraction from the reaction medium, which enables protein reuse. In some specific approaches, precisely in the ligand fishing assay, the bioanalytical method allows the ligands to be directly isolated from complex mixtures, including combinatorial libraries and natural products extracts without prior purification or fractionation steps. Most of these screening assays are based on liquid chromatography separation, and the binding events can be monitored through on-line or off-line methods. In the on-line approaches, solid supports containing the immobilized biological target are used as chromatographic columns most of the time. Several terms have been used to refer to such approaches, such as weak affinity chromatography, high-performance affinity chromatography, on-flow activity assays, and high-performance liquid affinity chromatography. On the other hand, in the off-line approaches, the binding event occurs outside the liquid chromatography system and may encompass affinity and activity-based assays in which the biological target is immobilized on magnetic particles or monolithic silica, among others. After the incubation step, the supernatant or the eluate from the binding assay is analyzed by liquid chromatography coupled to various detectors. Regardless of the selected bioanalytical approach, the use of solid supported proteins has significantly contributed to the development of automated and reliable screening methods that enable ligands to be isolated and characterized in complex matrixes without purification, thereby reducing costs and avoiding time-laborious steps. This review provides a critical overview of recently developed assays.

Formação profissional em uma atividade vivencial em saúde mental: Grupo Comunitário de Saúde Mental / Professional education in an experiential activity in mental health: Mental Health Community Group / Formación Profesional en una actividad vivencial en salud mental: Grupo Comunitario de Salud Mental

Objetivou-se compreender as experiências de estudantes e profissionais em processo de formação com uma atividade vivencial em saúde mental, denominada Grupo Comunitário de Saúde Mental (GCSM) e os desdobramentos de sua apropriação no percurso de formação profissional. Adotou-se uma abordagem qualitativa, de natureza exploratória, tendo como instrumento a entrevista aberta. Participaram cinco estudantes e 10 profissionais em formação de diferentes áreas da saúde. Para a análise utilizou-se o método de Análise de Conteúdo Temática. Foram elaboradas duas categorias: O lugar profissional no GCSM; A horizontalidade das relações no GCSM. Considera-se que a proposta vivencial, presente no modelo do GCSM apresenta contribuições tanto do ponto de vista técnico da formação, quanto em relação ao desenvolvimento humano dos profissionais. Destaca-se que este estudo traz avanços para se pensar a formação realizada em serviços-escola no campo da saúde mental e que tal compreensão pode colaborar com a consolidação do modelo psicossocial de atenção.

The objective of this study was to understand the experiences of students and professionals in process of education in an experiential activity in mental health, named Mental Health Community Group (MHCG), and the unfolding of its appropriation throughout professional education. A qualitative exploratory approach was adopted, and open interviews were used as data collection instrument. Study participants were five students and 10 professionals studying in different healthcare areas. Analysis was conducted using the thematic content analysis technique. Two categories were created: The professional place in the MHCG, and The horizontality of relationships in the MHCG. The experiential proposal, in the MHCG model, presents contributions both from the technical point of view of education, and in relation to the human development of professionals. This study promotes reflection on the education provided in teaching services in the mental health area and this understanding can contribute to consolidate the psychosocial care model.

Se trató de comprender las experiencias de estudiantes y profesionales en proceso de formación con una actividad vivencial en salud mental, denominada Grupo Comunitario de Salud Mental (GCSM) y los desdoblamientos de su apropiación en el curso de formación profesional. Se adoptó un enfoque cualitativo, de naturaleza exploratoria, teniendo como instrumento la entrevista abierta. Participaron cinco estudiantes y 10 profesionales en formación de diferentes áreas de la salud. Para el análisis se utilizó el método de Análisis de Contenido Temático. Se elaboraron dos categorías: El lugar profesional en el GCSM y la horizontalidad de las relaciones en el GCSM. Se considera que la propuesta vivencial, presente en el modelo del GCSM ofrece contribuciones tanto desde el punto de vista técnico de la formación, como con relación al desarrollo humano de los profesionales. Se destaca que este estudio trae avances para pensar la formación realizada en servicios-escuela en el campo de la salud mental y que tal comprensión puede colaborar con la consolidación del modelo psicosocial de atención.

A novel on-flow mass spectrometry-based dual enzyme assay.

This work describes a new simultaneous on-flow dual parallel enzyme assay based on immobilized enzyme reactors (ICERs) with mass spectrometry detection. The novelty of this work relies on the fact that two different enzymes can be screened at the same time with only one single sample injection and in less than 6 min. The system consisted of two immobilized capillary enzyme reactors (ICERs). More specifically, the ICERs comprised two different enzymes that were accommodated in parallel and were placed between a liquid chromatography (LC) system and a mass spectrometer (MS). The resulting system could be adapted to other types of enzyme reactors with different supports. All the elements in the system were interfaced by means of two 10-port/two-position switching valves. Different tubing dimensions allowed us to monitor the activity of each enzyme independently during the same analysis. Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) bioreactors were chosen as proof of concept. Acetylcholine (ACh) was used as substrate; the area of its protonated enzymatic hydrolysis product ion, choline, [M+H]+m/z 104.0, was monitored in the presence and absence of the standard cholinesterase inhibitor galantamine. This method proved to be an interesting tool for fast, simultaneous, and independent label-free dual enzyme inhibitor assay.

An improved immobilized enzyme reactor-mass spectrometry-based label free assay for butyrylcholinesterase ligand screening.

Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) are key cholinesterase enzymes responsible for the hydrolysis of acetylcholine into choline and acetic acid, an essential process for the restoration of the cholinergic neuron. The loss of cholinergic function in the central nervous system contributes to the cognitive decline associated with advanced age and Alzheimer's disease (AD). Inhibitions assays represent a significant role in the drug discovery process. Herein, we describe an improved label free method to screen and characterize new BChE ligands. The liquid chromatography system uses an immobilized capillary enzyme reactor (ICER) as a low affinity and high selectivity column coupled to a mass spectrometer (MS). The enzyme activity was evaluated by monitoring the choline's precursor ion [M + H]+m/z 104 for a brief period. The method was validated using two known cholinesterase inhibitors tacrine and galanthamine. The IC50 values were 0.03 ±â€¯0.006 µM and 0.88 ±â€¯0.2 for tacrine and galanthamine respectively, and Ki was 0.11 ±â€¯0.2 for galanthamine. The efficient combination of the huBChE-ICER with sensitive enzymatic assay detection such as MS, improved the reliable, fast identification of new ligands. Moreover, specific direct quantitation of the product contributes to the reduction of false positive and negative results.

Visitas Domiciliares de Agentes Comunitários de Saúde: Concepções de Profissionais e Usuários / Home visits by Community Health Agents: professionals’ and users’ conceptions / Visitas domiciliarias de Agentes Comunitarios de Salud: Concepciones de Profesionales y Usuarios

Objetivou-se analisar concepções que profissionais e usuários da Estratégia Saúde da Família (ESF) tem a respeito da finalidade das visitas domiciliares realizadas pelos Agentes Comunitários de Saúde (ACS). Neste estudo qualitativo foram realizadas entrevistas individuais semiestruturadas com sete profissionais e dezoito usuários de duas Unidades de Saúde da Família numa cidade de médio porte do interior paulista e observação participante de atividades realizadas pelos ACS. Por meio da análise temática de conteúdo, percebeu-se que apesar do suporte social que o ACS oferece à comunidade, as concepções dos participantes caracterizam as visitas como um trabalho protocolar, voltado ao indivíduo e à doença, distanciando-se das propostas de transformações da assistência em saúde, evidenciando as contradições de tal trabalho. O estudo possibilitou ampliar o olhar sobre as visitas domiciliares e tecer considerações sobre a importância de rever tais práticas, visando construir a ESF mais afinada com os pressupostos da Reforma Sanitária.

The objective of this study was to analyse the conceptions of workers’ and users’ of the Family Health Strategy (FHS) program regarding home visits by Community Health Agents (CHAs). In this qualitative research, individual semi-structured interviews were performed with seven professionals and eighteen users from two Health and Family Units in a mid-sized city in the countryside of São Paulo and participant observation of the CHAs’ activities were carried out. Thematic content analysis revealed that, despite the social support provided by the CHAs, participants see home visits as mechanical activities with bureaucratic purposes, aimed at the individual and the disease, thus deviating from the original purpose of healthcare transformation and exposing a contradictory aspect of such work. This study broadened the view regarding home visits by CHAs and highlighted the importance of reviewing this activity, to achieve a FHS in better alignment with the premises of the Health Reform.

El objetivo de este estudio fue analizar los conceptos que profesionales y usuarios de la Estrategia Salud de la Familia (ESF) tienen respecto a la finalidad de visitas a domicilio realizadas por Agentes Comunitarios de Salud (ACS). En este estudio cualitativo fueron realizadas entrevistas individuales semiestructuradas, con siete profesionales y dieciocho usuarios en dos Unidades de Salud de la Familia, en una ciudad de tamaño medio del interior paulista, y se observaron las actividades realizadas por los ACS. Mediante análisis de contenido temático se determinó que, a pesar del apoyo social comunitario ofrecido por los ACS, los participantes consideran las visitas como un trabajo protocolar, orientado al individuo y la enfermedad, alejándose de las propuestas de transformación de la asistencia de la salud, evidenciándose las contradicciones de tal trabajo. El estudio permitió ampliar la visión sobre las visitas a domicilio y realizar consideraciones acerca de la importancia de revisar esas prácticas, con la intención de construir una ESF más adecuada a los presupuestos de la Reforma Sanitaria.

Visitas domiciliares de agentes comunitários de saúde: concepções de profissionais e usuários / Home visits by community health agents: professionals' and users' conceptions / Visitas domiciliarias de agentes comunitarios de salud: concepciones de profesionales y usuarios

Objetivou-se analisar concepções que profissionais e usuários da Estratégia Saúde da Família (ESF) tem a respeito da finalidade das visitas domiciliares realizadas pelos Agentes Comunitários de Saúde (ACS). Neste estudo qualitativo foram realizadas entrevistas individuais semiestruturadas com sete profissionais e dezoito usuários de duas Unidades de Saúde da Família numa cidade de médio porte do interior paulista e observação participante de atividades realizadas pelos ACS. Por meio da análise temática de conteúdo, percebeu-se que apesar do suporte social que o ACS oferece à comunidade, as concepções dos participantes caracterizam as visitas como um trabalho protocolar, voltado ao indivíduo e à doença, distanciando-se das propostas de transformações da assistência em saúde, evidenciando as contradições de tal trabalho. O estudo possibilitou ampliar o olhar sobre as visitas domiciliares e tecer considerações sobre a importância de rever tais práticas, visando construir a ESF mais afinada com os pressupostos da Reforma Sanitária.

The objective of this study was to analyse the conceptions of workers and users& of the Family Health Strategy (FHS) program regarding home visits by Community Health Agents (CHAs). In this qualitative research, individual semi-structured interviews were performed with seven professionals and eighteen users from two Health and Family Units in a mid-sized city in the countryside of São Paulo and participant observation of the CHAs’ activities were carried out. Thematic content analysis revealed that, despite the social support provided by the CHAs, participants see home visits as mechanical activities with bureaucratic purposes, aimed at the individual and the disease, thus deviating from the original purpose of healthcare transformation and exposing a contradictory aspect of such work. This study broadened the view regarding home visits by CHAs and highlighted the importance of reviewing this activity, to achieve a FHS in better alignment with the premises of the Health Reform.

El objetivo de este estudio fue analizar los conceptos que profesionales y usuarios de la Estrategia Salud de la Familia (ESF) tienen respecto a la finalidad de visitas a domicilio realizadas por Agentes Comunitarios de Salud (ACS). En este estudio cualitativo fueron realizadas entrevistas individuales semiestructuradas, con siete profesionales y dieciocho usuarios en dos Unidades de Salud de la Familia, en una ciudad de tamaño medio del interior paulista, y se observaron las actividades realizadas por los ACS. Mediante análisis de contenido temático se determinó que, a pesar del apoyo social comunitario ofrecido por los ACS, los participantes consideran las visitas como un trabajo protocolar, orientado al individuo y la enfermedad, alejándose de las propuestas de transformación de la asistencia de la salud, evidenciándose las contradicciones de tal trabajo. El estudio permitió ampliar la visión sobre las visitas a domicilio y realizar consideraciones acerca de la importancia de revisar esas prácticas, con la intención de construir una ESF más adecuada a los presupuestos de la Reforma Sanitaria.

Biotransformation of labdane and halimane diterpenoids by two filamentous fungi strains.

Biotransformation of natural products by filamentous fungi is a powerful and effective approach to achieve derivatives with valuable new chemical and biological properties. Although diterpenoid substrates usually exhibit good susceptibility towards fungi enzymes, there have been no studies concerning the microbiological transformation of halimane-type diterpenoids up to now. In this work, we investigated the capability of Fusarium oxysporum (a fungus isolated from the rhizosphere of Senna spectabilis) and Myrothecium verrucaria (an endophyte) to transform halimane (1) and labdane (2) acids isolated from Hymenaea stigonocarpa (Fabaceae). Feeding experiments resulted in the production of six derivatives, including hydroxy, oxo, formyl and carboxy analogues. Incubation of 1 with F. oxysporum afforded 2-oxo-derivative (3), while bioconversion with M. verrucaria provided 18,19-dihydroxy (4), 18-formyl (5) and 18-carboxy (6) bioproducts. Transformation of substrate 2 mediated by F. oxysporum produced a 7α-hydroxy (7) derivative, while M. verrucaria yielded 7α- (7) and 3ß-hydroxy (8) metabolites. Unlike F. oxysporum, which showed a preference to transform ring B, M. verrucaria exhibited the ability to hydroxylate both rings A and B from substrate 2. Additionally, compounds 1-8 were evaluated for inhibitory activity against Hr-AChE and Hu-BChE enzymes through ICER-IT-MS/MS assay.

A experiência fenomenológica e o trabalho em grupo na saúde mental / La experiencia fenomenológica y el trabajo en grupo en la salud mental / The experience phenomenological and the group work at mental health

Resumo O objetivo do estudo foi compreender o potencial terapêutico da experiência vivida em uma prática em grupo de promoção à saúde mental, que se singulariza por ter a finalidade de atenção à experiência cotidiana. O corpus estudado formou-se pela observação participante por dois anos e seis meses e por nove entrevistas abertas em profundidade com participantes do grupo, fundamentando-se no referencial teórico metodológico da Fenomenologia. A pesquisa analisou como os participantes compreendem a proposta de atenção à experiência e disposição do coordenador no processo grupal, bem como a valorização da condição existencial em detrimento da doença. Essa sistematização pôde favorecer com um eixo terapêutico em saúde mental diferente das intervenções hermenêuticas e educativas clássicas, colaborando com alternativas de cuidado em saúde e comunidade via atenção à experiência.

Resumen El objetivo del estudio fue comprender el potencial terapéutico de la experiencia vivida en una práctica en grupo de promoción de la salud mental que se singulariza por tener la finalidad de atención a la experiencia cotidiana. El corpus estudiado se formó por la observación participante por dos años y seis meses y por nueve entrevistas abiertas en profundidad con participantes del grupo, fundamentándose en el referencial teórico metodológico de la Fenomenología. La investigación analizó cómo comprenden los participantes la propuesta de atención a la experiencia y disposición del coordinador en el proceso grupal, así como la valorización de la condición existencial en detrimento de la enfermedad. Esa sistematización se puede favorecer con un eje terapéutico en salud mental diferente de las intervenciones hermenéuticas y educativas clásicas, colaborando con alternativas de cuidado en salud y comunidad.

Abstract The objective of this research was to understand the therapeutic potential of Experience in a group of mental health that distinguishes for having the purpose of attention to everyday experience. The study corpus was formed by the participant observation for two years and six months and nine open interviews with the participants of the group, based on methodological theoretical framework of Phenomenology. Among its findings, the participants describe the proposal of attention to experience and the coordinator position, as well highlighting the existential condition rather than the disease. This study could collaborate with a therapeutic axis in mental health not centered in hermeneutic or education intervention and could favor with the understanding of care alternatives through attention in mental and community health.

Cuidado em saúde mental na Estratégia Saúde da Família: a construção da comunidade / Mental healthcare in the Family Health Strategy: the construction of the community

O objetivo do presente artigo é compreender a Saúde Mental na Estratégia Saúde da Família (ESF) a partir de um diálogo interdisciplinar entre Saúde Pública e Filosofia, visando refletir sobre o cuidado integral do ser humano. Buscou-se evidenciar fundamentações fenomenológicas acerca da singularidade humana, da alteridade e da comunidade. Para tal foram realizadas entrevistas abertas com profissionais, usuários e familiares, analisadas em profundidade, audiogravadas e transcritas na íntegra. Para o aprofundamento da análise selecionou-se recortes de três entrevistas considerando o envolvimento dos participantes e a riqueza dos conteúdos. A análise apontou a necessidade de reflexões críticas sobre o desenvolvimento de ações comunitárias, de se construir projetos voltados às comunidades para além da dicotomia saúde/doença e da discriminação e, ainda, para a compreensão do que vem a ser Saúde Mental na atenção primária.(AU)

The aim of the present article is to comprehend Mental Health in the Family Health Strategy (FHS), based on an interdisciplinary dialogue between Public Healthcare and Philosophy, in view of the possibility of providing the foundations for comprehensive care to Human Beings. We sought to evidence the philosophical foundations regarding human singularity, otherness, and community. To achieve this, open interviews were conducted with professionals, users and their relatives and were analyzed in depth, audiotaped, and transcribed. For an in-depth analysis, three interviews? cutouts were selected considering participants? involvement and richness of the content. The analysis indicated the need for critical reflection on the development of community actions, for community projects which aim beyond the health/disease dichotomy and discrimination, and, furthermore, to understand what Mental Health represents in primary healthcare.(AU)