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Ebola virus disease (EVD) causes outbreaks and epidemics in West Africa that persist until today. The envelope glycoprotein of Ebola virus (GP) consists of two subunits, GP1 and GP2, and plays a key role in anchoring or fusing the virus to the host cell in its active form on the virion surface. Toremifene (TOR) is a ligand that mainly acts as an estrogen receptor antagonist; however, a recent study showed a strong and efficient interaction with GP. In this context, we aimed to evaluate the energetic affinity features involved in the interaction between GP and toremifene by computer simulation techniques using the Molecular Fractionation Method with Conjugate Caps (MFCC) scheme and quantum-mechanical (QM) calculations, as well as missense mutations to assess protein stability. We identified ASP522, GLU100, TYR517, THR519, LEU186, LEU515 as the most attractive residues in the EBOV glycoprotein structure that form the binding pocket. We divided toremifene into three regions and evaluated that region i was more important than region iii and region ii for the formation of the TOR-GP1/GP2 complex, which might control the molecular remodeling process of TOR. The mutations that caused more destabilization were ARG134, LEU515, TYR517 and ARG559, while those that caused stabilization were GLU523 and ASP522. TYR517 is a critical residue for the binding of TOR, and is highly conserved among EBOV species. Our results may help to elucidate the mechanism of drug action on the GP protein of the Ebola virus and subsequently develop new pharmacological approaches against EVD.Communicated by Ramaswamy H. Sarma.

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The PI3K class I is composed of four PI3K isoforms that serve as regulatory enzymes governing cellular metabolism, proliferation, and survival. The hyperactivation of PI3Kα is observed in various types of cancer and is linked to poor prognosis. Unfortunately, the development inhibitors selectively targeting one of the isoforms remains challenging, with only few agents in clinical use. The main difficulty arises from the high conservation among residues at the ATP-binding pocket across isoforms, which also serves as target pocket for inhibitors. In this work, molecular dynamics and quantum calculations were performed to investigate the molecular features guiding the binding of selective inhibitors, alpelisib and GDC-0326, into the ATP-binding pocket of PI3Kα. While molecular dynamics allowed crystallographic coordinates to relax, the interaction eergy between each amino acid residues and inhibitors was obtained by combining the Molecular Fractionation with Conjugated Caps scheme with Density Functional Theory calculations. In addition, the atomic charge of ligands in the bound and unbound (free) was calculated. Results indicated that the most relevant residues for the binding of alpelisib are Ile932, Glu859, Val851, Val850, Tyr836, Met922, Ile800, and Ile848, while the most important residues for the binding of GDC-0326 are Ile848, Ile800, Ile932, Gln859, Glu849, and Met922. In addition, residues Trp780, Ile800, Tyr836, Ile848, Gln859 Val850, Val851, Ile932 and Met922 are common hotspots for both inhibitors. Overall, the results from this work contribute to improving the understanding of the molecular mechanisms controlling selectivity and highlight important interactions to be considered during the rational design of new agents.Communicated by Ramaswamy H. Sarma.

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Este trabalho buscou analisar as relações de cuidado no mandato da Atenção Psicossocial, considerando a centralidade de figuras femininas como principais cuidadoras de usuários da RAPS. Entendendo que a gestão desse cuidado é compartilhada com o Estado, partimos da hipótese de que a reformulação da política de saúde mental se ancora e reforça a histórica feminilização do cuidado, fortemente racializada e atravessada por desigualdades de classe e territórios. O objetivo geral desta pesquisa foi investigar o processo de familiarização e feminização do cuidado com RPB a partir de um trabalho etnográfico em um CAPS, observando o cotidiano de mulheres cuidadoras nesse serviço. Entre os objetivos específicos, buscou-se investigar a relação entre elas na gestão do cuidado em saúde mental, apontando para as discussões entre gênero, cuidado e trabalho, observando aproximações e distanciamentos entre categorias nativas e analíticas. Além disso, buscou-se refletir sobre a relação entre a política de saúde mental e a gestão estatal do cuidado enquanto mecanismos de regulação de gênero. As análises foram realizadas a partir da observação participante em um CAPS III do município do Rio de Janeiro. A pesquisa de campo privilegiou os espaços coletivos do CAPS, em especial a convivência e as atividades coletivas que contavam com a participação dos cuidadores, como a assembleia do CAPS, o grupo de família e o grupo de suporte de pares. Os achados da pesquisa apontam para a forma como essas mulheres, em seus distintos lugares sociais, respondem a esse mandato, criando relações de aliança e suporte mútuo, incluindo a ampliação de suas redes de apoio e cuidado no território, mas também compostas por tensões e disputas discursivas, sustentando a aposta política do cuidado dos sujeitos em sofrimento psíquico na comunidade. (AU)

This study aimed to analyse the care relationships within the framework of Psychosocial Attention, considering the central role of female figures as primary caregivers for users of the Psychosocial Care Network (RAPS). Understanding that the management of this care is shared with the State, we hypothesized that the reformulation of mental health policy is grounded in and reinforces the historical feminization of caregiving, strongly influenced by racialization and intersected by class and territorial inequalities. The overall objective of this research was to investigate the process of familiarization and feminization of care within the RAPS through an ethnographic study in a CAPS, observing the daily lives of women caregivers in this service. Among the specific objectives, we sought to investigate their role in mental health care management, pointing out the discussions regarding gender, care, and labor, while observing convergences and divergences between native and analytical categories. Furthermore, we aimed to reflect on the relationship between mental health policy and state management of care as mechanisms for gender regulation. The analyses were conducted through participant observation in a CAPS III in the municipality of Rio de Janeiro. The field research focused on the collective spaces of the CAPS, particularly interactions and collective activities involving caregivers, such as the CAPS assembly, family group, and peer support group. The research findings highlight how these women, from diverse social backgrounds, respond to this caregiving mandate, forming alliances and mutual support relationships, including the expansion of their support and care networks within the community. These relationships, however, also involve tensions and discursive disputes, underpinning the political commitment to providing care for individuals experiencing psychological distress within the community. (AU)

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Resumo Este artigo parte de uma pesquisa qualitativa que busca dar voz aos usuários, tornando-os atores através de uma pesquisa participativa. Trouxe à tona discursos estigmatizados e experiências afetadas pela perda de credibilidade testemunhal, conceito introduzido por Miranda Fricker como injustiça epistêmica. Todos os dados foram gerados através de um modelo de entrevista (MINI) no primeiro momento da pesquisa. No segundo momento, foi feita uma pesquisa participativa sob a lógica do cuidado que requer uma prática baseada na sensibilidade em relação às experiências do mundo dos usuários participantes. Diante desta perspectiva, ter voz emergiu como ponto essencial, e é nessa lógica que a pesquisa realizada no CAPS AD III, para que os usuários fizessem parte de uma abordagem participativa, teve a intenção de produzir mudanças.

Abstract This article is part of a qualitative research that seeks to give users a voice, making them actors through participatory research. It brought up stigmatized discourses and experiences affected by the loss of credibility, a concept introduced by Miranda Fricker as epistemic injustice. All data were generated through an interview model (MINI) in the first stage of the research, in the second moment, a participatory research was carried out under the logic of care that requires a practice based on sensitivity in relation to the experiences of the participating users in the world. Given this perspective, having a voice emerged as an essential point, and it is in this logic that the research carried out at CAPS AD III, so that users were part of a participatory approach, had the intention of producing changes.

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Este estudo traz dados de uma pesquisa de doutorado que objetivou conhecer a relação entre a precarização do trabalho e a saúde dos profissionais de um Centro de Atenção Psicossocial (CAPS). Trata-se de uma pesquisa de cunho qualitativo no campo da Saúde do Trabalhador. Foram realizadas entrevistas individuais semiestruturadas e observações sistemáticas com os trabalhadores. A partir dos depoimentos e das observações, foram percebidos problemas de ordem de gestão e de recursos materiais e humanos necessários para o bom funcionamento do serviço que geraram preocupação e sofrimento aos profissionais. Um outro componente que também colaborou para a precarização do trabalho desses profissionais foi o trabalho terceirizado. Além disso, os profissionais expressaram suas experiências e seu cotidiano de trabalho por meio de sofrimento, angústia e dificuldades para realização do trabalho. O sofrimento do trabalhador da saúde mental também tem suas particularidades, inerentes ao próprio tipo de trabalho, visto que tais profissionais estão expostos ao sofrimento e à dor de outras pessoas

This study brings data from a doctoral research which aimed to understand the relationship between the precarization of the work and the health of professionals from Psychosocial Care Center (CAPS). The study is qualitative research in the field of Occupational Health. Semi-structured individual interviews were carried out as well as systematic observation of the workers. Based on the interviewees' testimonies and analyzes, some management problems as well as lack of material and human resources necessary for the correct functioning of the service were noticed, which caused concern and suffering on the workers. Another component that also contributed to the precarious work of these professionals was outsourced work. Besides, workers expressed their experiences and their daily work through suffering, anguish, and difficulties in performing their work correctly. The suffering of mental health professionals also has its particularities, inherent to the type of work itself, since they are constantly exposed to other people's suffering and pain

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OBJECTIVE: To report our five-years experience on the use of NLRP3 inflammasome functional assays in the differential diagnosis of Brazilian patients with a clinical suspicion of CAPS. PATIENTS AND METHODS: The study included 9 patients belonging to 2 families (I, II) and 7 unrelated patients with a clinical suspicion of AID according to Eurofever/PRINTO classification, recruited between 2017 and 2022. The control group for the NLRP3 functional assay consisted of 10 healthy donors and for the CBA cytokines measurement of 19 healthy controls. Patients underwent clinical evaluation, genetic and functional analysis. RESULTS: All members of the family I received the diagnosis of Muckle-Wells Syndrome (MWS), carried the NLRP3 Thr348Met variant and resulted positive for the functional assay. The 2 patients of the family II resulted negative for the mutational screening but positive for the functional assay compatible with a MWS clinical phenotype. In 2 unrelated patients with NLRP3 mutations, including a novel mutation (Gly309Val, Asp303His), a positive functional test confirmed the clinical diagnosis of NOMID. 3 unrelated MWS and 1 FCAS patients resulted negative to the genetic screening and positive for the functional test. One patient with a FCAS-like phenotype harbored the NLRP12 His304Tyr variant confirming the diagnosis of FCAS2. CONCLUSION: The NLRP3 inflammasome functional assay can assist the clinical diagnosis of CAPS even in patients with unknown genetic defects.

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OBJECTIVE: Produce sold as plastic-wrapped packs of two to four individual items (i.e., produce micro-packs) that are low cost and placed at checkout may appeal to shoppers with budget constraints and provide a second chance to purchase items available elsewhere in the store. This study examined the impact of an intervention that placed produce micro-packs at checkout and promoted them in grocery stores across New Mexico, USA. DESIGN: This quasi-experimental study placed produce micro-packs at checkout end-caps in thirteen stores (group 1), with eight stores serving as controls (group 2) from 1 July 2019 through 31 January 2020 (first phase). The intervention was extended to group 2 stores from 1 February 2020 through 30 June 2020 (second phase). Cashiers were directed to upsell the micro-packs to Special Supplemental Nutrition Program for Women, Infants, and Children recipients who had unspent cash value benefits for produce purchases. SETTING: Twenty-one grocery stores across New Mexico. PARTICIPANTS: Twenty-one produce items sold as micro-packs in stores from July 2019 through June 2020. RESULTS: A random effects model showed that the daily sales of micro-packs increased by 47 % during each intervention period. Group 2 stores had lower sales than group 1 stores during the first phase of the intervention. Once extended to group 2 stores, sales of micro-packs in those stores increased and sales in group 1 stores continued at the higher level. CONCLUSIONS: Placing produce micro-packs at checkout may increase produce sales and support health promotion efforts by public and private stakeholders.

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A pesquisa procurou explorar as experiências de adoecimento com base no ponto de vista dos usuários de um CAPS AD III. A metodologia empregada neste estudo se baseia em um desenho qualitativo e se divide em duas etapas. Na primeira, foi realizada uma entrevista semiestruturada com os participantes — Entrevista Narrativa de Adoecimento McGill-MINI —, e, na segunda, os participantes foram parte integrante do processo de validação, análise dos resultados e elaboração do arcabouço temário. Os resultados anunciam narrativas atravessadas por desamparo psíquico, abandono familiar, perdas e falta de credibilidade, efeito de um processo excludente em que a droga se sobrepõe ao sujeito. A pesquisa participativa sob a lógica do cuidado (Tangvald-Pedersen & Bongaardt, 2016) possibilitou um diálogo reflexivo acerca da experiência de adoecimento aproximando pesquisadores e participantes, que são como diferentes contadores de histórias, permitindo que a tessitura do fenômeno descrito pudesse enriquecer a compreensão uns dos outros.

Resumos This research explores the experiences of illness from the point of view of users of a CAPS AD III. Based on a qualitative design, the study comprised two stages: in the first, a Narrative Interview of Illness McGill-MINI, a semi-structured interview protocol, was carried out with the participants; in the second, the participants took part in the validation process, analysis of results and elaboration of the thematic framework. The results reveal narratives crossed by psychic helplessness, family abandonment, losses, and lack of credibility — the effect of an excluding process in which the drug overrides the subject. Participatory research under the logic of care (Tangvald-Pedersen & Bongaardt, 2016) enabled a reflective dialogue on the experience of illness, bringing together researchers and participants as different storytellers, allowing the weaving of the phenomenon to enrich their mutual understanding.

Cette recherche explore les expériences de la maladie du point de vue des utilisateurs d'un CAPS AD III. Basée sur un design qualitatif, l'étude s'est déroulée en deux étapes : dans la première, un entretien narratif semi-structurée (Narrative Interview of Illness McGill-MINI) a été réalisée avec les participants; dans la seconde, les participants ont pris part au processus de validation, d'analyse des résultats et d'élaboration du cadre thématique. Les résultats révèlent des récits traversés par l'impuissance psychique, l'abandon familial, les pertes et le manque de crédibilité — l'effet d'un processus d'exclusion dans lequel la drogue chevauche le sujet. La recherche participative sous la logique du soin (Tangvald-Pedersen & Bongaardt, 2016) a permis un dialogue réflexif sur l'expérience de la maladie, réunissant chercheurs et participants comme des différents conteurs, permettant au tissage du phénomène d'enrichir leur compréhension mutuelle.

La investigación buscó explorar las experiencias de enfermedad a partir del punto de vista de los usuarios de CAPS AD III. La metodología utilizada en este estudio se basa en un diseño cualitativo y se divide en dos etapas. En la primera, se realizó una entrevista semiestructurada con los participantes — Entrevista Narrativa de Enfermedad McGill-MINI — y, en la segunda, los participantes fueron parte integral del proceso de validación, análisis de resultados y elaboración del marco temático. Los resultados anuncian narrativas atravesadas por el desamparo psíquico, el abandono familiar, las pérdidas y la falta de credibilidad, efecto de un proceso excluyente en el que la droga se superpone al sujeto. La investigación participativa bajo la lógica del cuidado (Tangvald-Pedersen & Bongaardt, 2016) permitió un diálogo reflexivo sobre la experiencia de la enfermedad, reuniendo a investigadores y participantes, que son como diferentes narradores, permitiendo que la tesitura del fenómeno descrito pudiera enriquecer la comprensión de cada uno.

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Leishmanolysin, also known as major promastigote protease (PSP) or gp63, is the most abundant surface glycoprotein of Leishmania spp., and has been extensively studied and recognized as the main parasite virulence factor. Characterized as a metalloprotease, gp63 can be powerfully inactivated in the presence of a metal chelator. In this study, we first used the structural parameters of a 7-hydroxycoumarin derivative, L1 compound, to evaluate the theoretical-computational experiments against gp63, comparing it with an available metal chelator already described. The methodology followed was (i) analysis of the three-dimensional structure of gp63 as well as its active site, and searching the literature and molecular databases for possible inhibitors; (ii) molecular docking simulations and investigation of the interactions in the generated protein-ligand complexes; and (iii) the individual energy of the gp63 amino acids that interacted most with the ligands of interest was quantified by ab initio calculations using Molecular Fraction with Conjugated Caps (MFCC). MFCC still allowed the final quantum balance calculations of the protein interaction to be obtained with each inhibitor candidate binder. L1 obtained the best energy quantum balance result with -2 eV, followed by DETC (-1.4 eV), doxycycline (-1.3 eV), and 4-terpineol (-0.6 eV), and showed evidence of covalent binding in the enzyme active site. In vitro experiments confirmed L1 as highly effective against L. amazonensis parasites. The compound also exhibited a low cytotoxicity profile against mammalian RAW and 3T3 cells lines, presenting a selective index of 149.19 and 380.64 µM, respectively. L1 induced promastigote forms' death by necrosis and the ultrastructural analysis revealed disruption in membrane integrity. Furthermore, leakage of the contents and destruction of the parasite were confirmed by Spectroscopy Dispersion analysis. These results together suggested L1 has a potential effect against L. amazonensis, the etiologic agent of diffuse leishmaniasis, and the only one that currently does not have a satisfactory treatment.

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RESUMO: Este trabalho tem o objetivo de discutir as incidências do laço social como instância que comparece em ato no trabalho do psicanalista, no contexto da saúde mental, e assegura um lugar de sujeito para usuários de Centro de Apoio Psicossocial - CAPS. Para o percurso metodológico, foram adotados o método qualitativo, referencial teórico psicanalítico, breve apresentação e discussão de um caso clínico. O resultado aponta para a necessidade de construção do laço social como possibilidade para o emergir do sujeito a partir de uma invenção sustentada em um discurso que estabelecerá um meio de regulação de gozo.

Abstract: This work aims to discuss the incidence of the social bond as an instance that is present in the psychoanalyst's work, in the context of mental health, and ensures a place of subject for users of the Psychosocial Support Center. For the methodological path, the qualitative method, psychoanalytic theoretical framework, brief presentation and discussion of a clinical case was adopted. The result points to the need to build the social bond as a possibility for the subject to emerge, based on an invention sustained in a discourse that will establish a means of regulating enjoyment.

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