Therapeutic potential of LINS01 histamine H3 receptor antagonists as antineoplastic agents for triple negative breast cancer.

The aims of this work were to evaluate the expression of histamine H3 receptor (H3R) in triple negative breast cancer (TNBC) samples and to investigate the antitumoral efficacy and safety of the LINS01 series of H3R antagonists, through in silico, in vitro, and in vivo approaches. Antitumor activity of LINS01009, LINS01010, LINS01022, LINS01023 was assayed in vitro in 4T1 and MDA-MB-231 TNBC cells (0.01-100 µM), and in vivo in 4T1 tumors orthotopically established in BALB/c mice (1 or 20 mg/kg). Additionally, H3R expression was assessed in 50 human TNBC samples. We have described a higher H3R mRNA expression in basal-like/TNBC tumors vs. matched normal tissue using TCGA Pan-Cancer Atlas data, and a higher H3R expression in human tumor samples vs. peritumoral tissue evidenced by immunohistochemistry associated with poorer survival. Furthermore, while all the essayed compounds showed antitumoral properties, LINS01022 and LINS01023 exhibited the most potent antiproliferative effects by: i) inducing cell apoptosis and suppressing cell migration in 4T1 and MDA-MB-231 TNBC cells, and ii) inhibiting cell growth in paclitaxel-resistant 4T1 cells (potentiating the paclitaxel antiproliferative effect). Moreover, 20 mg/kg LINS01022 reduced tumor size in 4T1 tumor-bearing mice, exhibiting a safe toxicological profile and potential for druggability estimated by ADME calculations. We conclude that the H3R is involved in the regulation of TNBC progression, offering promising therapeutic potential for the novel LINS01 series of H3R antagonists.

Hepatic expression of tumor necrosis factor-α and evaluation of MAPK-p38 and NFκB signaling pathways in autoimmune hepatitis.

OBJECTIVES: Autoimmune hepatitis (AIH) is a necroinflammatory disease that occurs when genetically susceptible individuals are exposed to an environmental trigger. It is a rare disease, and its epidemiological aspects are nearly unknown in Northeast Brazil. In the literature, the activation of components of the inflammatory cascade pathways, including interleukins such as TNF-α and signaling factors like MAPK-p38 and NFκB, in the pathogenesis of AIH is well described in animal models. This study evaluated, for the first time, the immunostaining of TNF-α, MAPK-p38, and NFκB in immunohistochemical analysis of liver biopsies from AIH patients. The activation of the MAPK-p38 pathway was also studied through immunoassay analysis in the peripheral blood of AIH patients. METHODS AND RESULTS: Data from medical records of 25 AIH patients were analyzed. Histological and immunohistochemical analysis of liver tissue obtained from biopsies was performed to detect NFκB, MAPK-p38, and TNF-α. Immunoassay analysis of the MAPK-p38 pathway was performed in peripheral blood from 18 AIH patients and 8 healthy volunteers. Medical record analysis showed an average age of 33.3 years, with a female predominance in a ratio of 7.3:1. Concomitance with other autoimmune diseases was observed in 36 % of patients, with thyroid disorders being the most prominent among them, and an 8 % indication for liver transplantation. In the evaluation of autoantibodies, ANA was detected in 52 %, followed by SMA at 20 %, and Anti-LKM-1 at 16 %. Liver biopsy findings were like the global literature, with interface hepatitis and lymphoplasmacytic infiltration observed. Immunohistochemical analysis showed immunostaining for NFκB, MAPK-p38, and TNF-α, corroborating the inflammatory and immunological characteristics of the disease. Immunoassay analysis in peripheral blood confirmed the activation of the MAPK-p38 signaling pathway, with a statistically significant difference between AIH patients and healthy controls. CONCLUSIONS: The epidemiological and histological findings of AIH in this study in Northeast Brazil were like global population data. Immunohistochemical analysis of liver tissue and immunoassay analysis in peripheral blood confirmed the activation of TNF-α and the NFκB and MAPK-p38 signaling pathways in AIH patients.

RNA-regulatory exosome complex suppresses an apoptotic program to confer erythroid progenitor cell survival in vivo.

The RNA-regulatory exosome complex (EC) posttranscriptionally and cotranscriptionally processes and degrades RNAs in a context-dependent manner. Although the EC functions in diverse cell types, its contributions to stem and progenitor cell development are not well understood. Previously, we demonstrated that the transcriptional regulator of erythrocyte development, GATA1, represses EC subunit genes, and the EC maintains erythroid progenitors in vitro. To determine if this mechanism operates in vivo, we used the hematopoietic-specific Vav1-Cre and "conditional by inversion" mouse system to ablate Exosc3, encoding an EC structural subunit. Although Exosc3C/C Cre+ embryos developed normally until embryonic day 14.5, Exosc3 ablation was embryonic lethal and severely reduced erythromyeloid progenitor activity. RNA sequencing analysis of Exosc3-ablated burst-forming unit-erythroid revealed elevated transcripts encoding multiple proapoptotic factors, and the mutant erythroid progenitors exhibited increased apoptosis. We propose that the EC controls an ensemble of apoptosis-regulatory RNAs, thereby promoting erythroid progenitor survival and developmental erythropoiesis in vivo.

Enfrentamento da violência contra a mulher: a atuação de coletivo de mulheres / Afrontando la violencia contra las mujeres: el trabajo de un colectivo de mujeres / Confronting violence against women: the work of a women's collective

Objetivo: descrever a atuação do Coletivo de Mulheres do Calafate para o enfrentamento da Violência Contra a Mulher. Método: estudo qualitativo, descritivo, realizado em Salvador, Bahia, Brasil, entre setembro e novembro de 2020. Compôs a pesquisa os relatos de nove mulheres que possuem ou possuíram vínculo institucional com o referido coletivo, sendo fundamentado na História Oral Temática, utilizando-se o meio digital para assinatura do TCLE e entrevista. Resultados: a atuação do Coletivo para o enfrentamento da violência contra a mulher inclui estratégias no âmbito da comunidade, emergindo assim as categorias: espaço para escuta às mulheres; espaço para compartilhar vivências de mulheres; espaço para articulação com os serviços de referência; e espaço para encaminhamento e/ou acompanhamento de mulheres nos serviços. Considerações Finais: o Coletivo promoveu ações de enfrentamento da violência contra a mulher, sinalizando a importância de organizações sociais feministas enquanto cenário de referência na comunidade.

Objetivo: describir el trabajo del Colectivo de Mujeres de Calafate en el afrontamiento a la violencia contra las mujeres. Método: Estudio cualitativo y descriptivo realizado en Salvador, Bahía, Brasil, entre septiembre y noviembre de 2020. La investigación se basó en los relatos de nueve mujeres que tienen o han tenido vínculos institucionales con el mencionado colectivo, a partir de la Historia Oral Temática, utilizando medios digitales para firmar el ICF y la entrevista. Resultados: el trabajo del Colectivo para afrontar la violencia contra las mujeres incluye estrategias dentro de la comunidad, y surgieron las siguientes categorías: espacio para escuchar a las mujeres; espacio para compartir las experiencias de las mujeres; espacio de enlace con los servicios de derivación; y espacio para derivar y/o acompañar a las mujeres a los servicios. Consideraciones finales: el Colectivo promovió acciones para afrontar la violencia contra las mujeres, lo que señala la importancia de las organizaciones sociales feministas como escenario de referencia en la comunidad.

Objective: to describe the work of the Calafate Women's Collective to confront violence against women. Method: a qualitative, descriptive study carried out in Salvador, Bahia, Brazil, between September and November 2020. The research included the reports of nine women who have or have had an institutional link with the aforementioned collective, based on Thematic Oral History, using the digital media for signing the informed consent form and interviews. Results: The Collective's work to confront violence against women includes strategies within the community, thus emerging the categories: space for listening to women; space for sharing women's experiences; space for liaison with referral services; and space for referral and/or accompaniment of women to services. Final considerations: the Collective promoted actions to confront violence against women, signaling the importance of feminist social organizations as a reference point in the community.

Cuidados de enfermagem a gestantes em tempos de pandemia do SARS-COV-2 / Cuidado de enfermería para mujeres embarazadas en tiempos de pandemia de sars-cov-2 / Cuidado de enfermería para mujeres embarazadas en tiempos de pandemia de sars-cov-2

Objetivo: Identificar, na literatura, os cuidados de enfermagem no período gestacional, no contexto pandêmico. E expor aos leitores, a importância dele, visando prevenir a forma grave da doença e seus desfechos, evitando assim, a ocorrência de morbimortalidade. Método: Para obtenção dos dados foi realizada uma revisão integrativa, seguindo a identificação da questão norteadora, com critério de inclusão os artigos selecionados nas bases de dados MEDLINE, LILACS, BDENF, PUBMED e manuais publicados pelo Ministério da Saúde e organização de saúde entre os anos de 2020 e 2021. Resultado: De acordo com os artigos selecionados e revisados, as boas práticas de higiene, bem como a precoce dos casos suspeitos são ações de suma importância a serem adotados pela equipe de enfermagem, diminuindo os desfechos mais graves pós-infecção. Conclusão: A equipe de enfermagem tem em sua importância a promover a conscientização dos benefícios da vacinação e dos cuidados para prevenção de gestantes contra COVID-19 e pós contrair o vírus, promovendo um cuidado humanizado(AU)

Objective: To identify, in the literature, nursing care during pregnancy in the pandemic context. And expose to readers, its importance, aiming to prevent the severe form of the disease and its outcomes, thus avoiding the occurrence of morbidity and mortality. Method: To obtain the data, an integrative review was performed, following the identification of the guiding question, with inclusion criteria for articles selected in the MEDLINE, LILACS, BDENF, PUBMED databases and manuals published by the Ministry of Health and health organization among the years 2020 and 2021. Result: According to the selected and reviewed articles, good hygiene practices, as well as vaccination, social distancing and early screening of suspected cases are extremely important actions to be adopted by the nursing team, reducing the most severe post-infection outcomes. Conclusion: The nursing team has in its importance to promote awareness of the benefits of vaccination and care for the prevention of pregnant women against COVID-19 and after contracting the virus, promoting humanized care.(AU)

Objetivo: Identificar los cuidados de enfermería durante el embarazo en el contexto pandémico en la literatura. Y exponer a los lectores, su importancia, con el objetivo de prevenir la forma grave de la enfermedad y sus desenlaces, evitando así la ocurrencia de morbimortalidad. Método: Para la obtención de los datos se realizó una revisión integradora, previa identificación de la pregunta orientadora, con criterios de inclusión para los artículos seleccionados en las bases de datos MEDLINE, LILACS, BDENF, PUBMED y manuales publicados por el Ministerio de Salud y organización sanitaria entre los años 2020 y 2021. Resultado: De acuerdo con los artículos seleccionados y revisados, las buenas prácticas de higiene, así como la vacunación, el distanciamiento social y el cribado precoz de los casos sospechosos son acciones de suma importancia a ser adoptadas por el equipo de enfermería, reduciendo las consecuencias de la infección. . Conclusión: El equipo de enfermería es importante para promover el conocimiento de los beneficios de la vacunación y el cuidado para la prevención de la gestante contra COVID-19 y luego de contraer el virus, promoviendo el cuidado humanizado(AU)

Molecular Detection of Tick-Borne Agents in Cats from Southeastern and Northern Brazil.

Even though the epidemiology of tick-borne agents (TBA) in dogs has been extensively investigated around the world, the occurrence, vectors involved, and molecular identity of these agents in cats remains elusive in many regions. Among TBA, Ehrlichia, Anaplasma, Babesia, Cytauxzoon, and Hepatozoon are responsible for diseases with non-specific clinical signs in cats, making essential the use of molecular techniques for accurate diagnosis and proper treatment. The present work aimed to investigate the occurrence and molecular identity of tick-borne agents (Ehrlichia, Anaplasma, Babesia/Theileria, Cytauxzoon, and Hepatozoon) in cats from southeastern (states of São Paulo (SP) and Minas Gerais (MG)) and northern (state of Rondônia (RO)) Brazil. For this purpose, 390 blood samples were collected from domiciled cats in MG (n = 155), SP (n = 151), and RO(n = 84) states, submitted to DNA extraction and PCR assays for Ehrlichia spp. (dsb gene), Anaplasma spp. (rrs gene), piroplasmids (18S rRNA gene), and Hepatozoon spp. (18S rRNA gene), sequencing, and phylogenetic inferences. The overall positivity for Anaplasma spp., Ehrlichia spp., Babesia/Theileria spp., Cytauxzoon spp., and Hepatozoon spp. were 7.4% (12.3% (MG) and 6.6% (SP)), 2% (4.5% (MG) and 0.6% (SP)), 0.7% (0.6% (MG), 0.6% (SP) and 1.2% (RO)), 27.2% (41.9% (MG), 24.5% (SP) and 4.8% (RO), and 0%, respectively. The phylogenetic analysis grouped the obtained sequences with 'Candidatus Anaplasma amazonensis', A. platys, B. vogeli, and Cytauxzoon sp. previously detected in wild felids from Brazil. qPCR specific for E. canis based on the dsb gene confirmed the molecular identity of the detected ehrlichial agent. The present study expanded the list and geographical distribution of hemoparasites in cats. 'Candidatus Anaplasma amazonensis', recently detected in sloths from northern Brazil, was described for the first time in cats. This is the first report of piroplasmids infecting cats in northern Brazil. Coinfection by Cytauxzoon and other TBA (Ehrlichia, Anaplasma, and B. vogeli) reported in the present study raises the need for veterinary practitioners' awareness of cats parasitized by multiple TBA.

Curso de biossegurança para equipes de saúde bucal em tempos de covid-19: relato de experiência / Biosafety course for oral health teams in covid-19 times: an experience report / Curso de bioseguridad para equipos de salud bucal en tiempos de covid-19: informe de experiencia

Este relato apresenta a experiência da elaboração e desenvolvimento da primeira etapa (turmas 1 a 5) do Curso de Biossegurança para Equipes de Saúde Bucal em tempos de Covid-19, por docentes da Escola de Saúde Pública do Estado da Bahia Professor Jorge Novis (ESPBA), instituição pertencente à Superintendência de Recursos Humanos da Secretaria de Saúde do Estado da Bahia (Sesab). A experiência decorre do enfrentamento da pandemia da Covid-19 no estado da Bahia, considerando as formas de transmissão da doença pelo contato direto entre pessoas, pela fala, tosse, espirro e aerossóis. As glândulas salivares são reservatórios do SARS-CoV-2, vírus responsável pela doença, e o ambiente odontológico possui grande risco de propagação desse microrganismo. Trata-se de um curso autoinstrucional, que utiliza a plataforma Moodle EAD-SUS da ESPBA, composto por cinco videoaulas, contemplando a parte operativa e a prática clínica sobre biossegurança em tempos de Covid-19. O curso foi ofertado por regiões de saúde, priorizando as turmas iniciais de acordo com os indicadores epidemiológicos do número de casos. Foi contabilizado o número de inscritos por região de saúde, o número de acessos e o número de avaliações de conteúdo e do curso. Notou-se interesse dos profissionais da área na temática de biossegurança, mas questões estruturais e de sobrecarga de trabalho podem ter comprometido a realização de todas as etapas do curso. Ainda assim, o curso obteve ótima avaliação pelos discentes, revelando sucesso da ação educativa.

This report shows the experience of report of the elaboration and development of the first stage (classes 1 to 5) of the "Biosafety Course for Oral Health Teams in times of Covid-19", by professors from the School of Public Health of the State of Bahia Professor Jorge Novis (ESPBA), an institution belonging to Superintendence of Human Resources of the Health Department of the State of Bahia. The experience stems from coping with the Covid-19 pandemic in the State of Bahia, Brazil, considering the forms of transmission of the disease through direct contact with people, through speech, coughing, sneezing and aerosols. Salivary glands are reservoirs of SARS-CoV-2, the virus responsible for the disease, and the dental environment has a high risk of spreading this microorganism. It was a self-instructional course using ESPBA's Moodle EAD-SUS platform, consisting of five video classes, covering the operational part and clinical practice on Biosafety in Covid-19 times. The course was offered by health regions, prioritizing the initial classes according to the epidemiological indicators of the number of cases. The number of enrolled students by health regions, the number of accesses and the number of content and course evaluations were estimated. The interest of professionals in the area in the theme of Biosafety was noted; however, structural and work overload issues may have compromised the performance of all stages of the course. The course obtained excellent evaluation by the students, showing the success of the educational action.

Este informe presenta la experiencia de la elaboración y desarrollo de la primera etapa (clases 1 a 5) del Curso de Bioseguridad para Equipos de Salud Bucal en tiempos de Covid-19 por profesores de la Escuela de Salud Pública del Estado de Bahía Profesor Jorge Novis (ESPBA), institución perteneciente a Superintendencia de Recursos Humanos de la Secretaría de Salud del Estado de Bahía (Sesab). La experiencia surge del afrontamiento de la pandemia de covid-19 en el estado de Bahía, considerando las formas de transmisión de la enfermedad mediante el contacto directo entre personas, habla, tos, estornudos y aerosoles. Las glándulas salivales son reservorios del Sars-CoV-2, el virus responsable de la enfermedad, y el entorno dental tiene un alto riesgo de propagar este microorganismo. Este curso de autoaprendizaje utiliza la plataforma Moodle EAD-SUS de ESPBA y consta de cinco videoclases, cubriendo la parte operativa y práctica clínica sobre bioseguridad en tiempos de covid-19. El curso fue impartido en regiones sanitarias, priorizando las clases iniciales según los indicadores epidemiológicos del número de casos. Se contabilizó el número de inscritos por regiones sanitarias, el número de accesos y el número de evaluaciones de contenido y cursos. Se observó que los profesionales del área se interesaban en el tema de bioseguridad, pero los problemas estructurales y de sobrecarga de trabajo pueden haber comprometido el desempeño de todas las etapas del curso. El programa obtuvo una excelente evaluación por parte de los estudiantes, revelando el éxito de la acción educativa.

RNA-regulatory exosome complex confers cellular survival to promote erythropoiesis.

Cellular differentiation requires vast remodeling of transcriptomes, and therefore machinery mediating remodeling controls differentiation. Relative to transcriptional mechanisms governing differentiation, post-transcriptional processes are less well understood. As an important post-transcriptional determinant of transcriptomes, the RNA exosome complex (EC) mediates processing and/or degradation of select RNAs. During erythropoiesis, the erythroid transcription factor GATA1 represses EC subunit genes. Depleting EC structural subunits prior to GATA1-mediated repression is deleterious to erythroid progenitor cells. To assess the importance of the EC catalytic subunits Dis3 and Exosc10 in this dynamic process, we asked if these subunits function non-redundantly to control erythropoiesis. Dis3 or Exosc10 depletion in primary murine hematopoietic progenitor cells reduced erythroid progenitors and their progeny, while sparing myeloid cells. Dis3 loss severely compromised erythroid progenitor and erythroblast survival, rendered erythroblasts hypersensitive to apoptosis-inducing stimuli and induced γ-H2AX, indicative of DNA double-stranded breaks. Dis3 loss-of-function phenotypes were more severe than those caused by Exosc10 depletion. We innovated a genetic rescue system to compare human Dis3 with multiple myeloma-associated Dis3 mutants S447R and R750K, and only wild type Dis3 was competent to rescue progenitors. Thus, Dis3 establishes a disease mutation-sensitive, cell type-specific survival mechanism to enable a differentiation program.

Cardiovascular Physiotherapy on Respiratory Sinus Arrhythmia of Patients Undergoing Coronary Artery Bypass Grafting.

INTRODUCTION: Patients in the postoperative period of coronary artery bypass grafting (CABG) present respiratory and autonomic dysfunctions. In this sense, cardiovascular physiotherapy has been offered as an indispensable differential for the improvement of the prognosis of this population. Heart rate variability is a simple, noninvasive method to analyze autonomic modulation, as well as the accentuation maneuver of respiratory sinus arrhythmia, which demonstrates the parasympathetic autonomic control over the heart. Five patients undergoing cardiac surgery performed a protocol of cardiovascular physiotherapy in the postoperative period and had their data referring to the preoperative period, the 1st and 4th postoperative days analyzed.

Hidden wounds of violence: Abnormal motor oscillatory brain activity is related to posttraumatic stress symptoms.

Victims of urban violence are at risk of developing Posttraumatic Stress Disorder (PTSD), one of the most debilitating consequences of violence. Considering that PTSD may be associated with inefficient selection of defensive responses, it is important to understand the relation between motor processing and PTSD. The present study aims to investigate the extent to which the severity of posttraumatic stress symptoms (PTSS) is related to motor preparation against visual threat cues in victims of urban violence. Participants performed a choice reaction time task while ignoring a picture that could be threating or neutral. The EEG indices extracted were the motor-related amplitude asymmetry (MRAA) in the alpha frequency range, and the lateralized readiness potential (LRP). We observed a linear relation between longer LRP latency and a slower reaction time, selectively during threat processing (compared to neutral) in low PTSS, but not in high PTSS participants. Alpha MRAA suppression and the PTSS were also linearly related: the smaller the alpha MRAA suppression in the threat condition relative to neutral, the greater the PTSS. These results provide evidence that threatening cues affect motor processing that is modulated by the severity of PTSS in victims of urban violence.

Psychosocial care for people with suicidal behavior from the perspective of users and health professionals. / Atenção psicossocial às pessoas com comportamento suicida na perspectiva de usuários e profissionais de saúde.

OBJECTIVE: To understand the implications of the assistance provided to people with suicidal behavior within the scope of the Psychosocial Care Network, from the perspective of users and health professionals. METHOD: A qualitative research, under the theoretical framework of complex and methodological thinking in Grounded Theory. Interviews were conducted from May to December 2017, with users assisted due to suicidal behavior and with health professionals in psychosocial care settings. The comparative data analysis technique was used. RESULTS: 18 users and health professionals participated. Non-acceptance intensifies users' introspection, demotivation and hopelessness, increasing the difficulty of exposing their desires. In situations of embracement, availability and bonding with professionals, patients feel more open, to the point of giving new meanings to life and reducing thoughts of death. CONCLUSION: Weaknesses and potentialities were noticed in the care provided by health professionals to users with suicidal behavior, within the scope of the Psychosocial Care Network. The need for management committed to the quality of care in the face of the risk of suicide stands out.

Post-transcriptional control of cellular differentiation by the RNA exosome complex.

Given the complexity of intracellular RNA ensembles and vast phenotypic remodeling intrinsic to cellular differentiation, it is instructive to consider the role of RNA regulatory machinery in controlling differentiation. Dynamic post-transcriptional regulation of protein-coding and non-coding transcripts is vital for establishing and maintaining proteomes that enable or oppose differentiation. By contrast to extensively studied transcriptional mechanisms governing differentiation, many questions remain unanswered regarding the involvement of post-transcriptional mechanisms. Through its catalytic activity to selectively process or degrade RNAs, the RNA exosome complex dictates the levels of RNAs comprising multiple RNA classes, thereby regulating chromatin structure, gene expression and differentiation. Although the RNA exosome would be expected to control diverse biological processes, studies to elucidate its biological functions and how it integrates into, or functions in parallel with, cell type-specific transcriptional mechanisms are in their infancy. Mechanistic analyses have demonstrated that the RNA exosome confers expression of a differentiation regulatory receptor tyrosine kinase, downregulates the telomerase RNA component TERC, confers genomic stability and promotes DNA repair, which have considerable physiological and pathological implications. In this review, we address how a broadly operational RNA regulatory complex interfaces with cell type-specific machinery to control cellular differentiation.

Atenção psicossocial às pessoas com comportamento suicida na perspectiva de usuários e profissionais de saúde / Atención psicosocial para personas con conducta suicida desde la perspectiva de usuarios y profesionales de la salud / Psychosocial care for people with suicidal behavior from the perspective of users and health professionals

RESUMO Objetivo Compreender as implicações da assistência prestada às pessoas com comportamento suicida no âmbito da Rede de Atenção Psicossocial, na perspectiva de usuários e profissionais de saúde. Método Pesquisa qualitativa, sob o referencial teórico do pensamento complexo e metodológico na Grounded Theory. Foram realizadas entrevistas, no período de maio a dezembro de 2017, com usuários assistidos por comportamento suicida e com profissionais de saúde em cenários da atenção psicossocial. Utilizou-se a técnica de análise comparativa dos dados. Resultados Participaram 18 usuários e 15 profissionais de saúde. O não acolhimento intensifica a introspecção, desmotivação e desesperança nos usuários, aumentando a dificuldade de exporem seus anseios. Em situações de acolhimento, disponibilidade e vinculação com os profissionais, os mesmos sentem-se mais abertos, a ponto de darem novos sentidos à vida e reduzirem os pensamentos de morte. Conclusão Foram identificadas fragilidades e potencialidades no atendimento prestado por profissionais de saúde aos usuários com comportamento suicida, no âmbito da Rede de Atenção Psicossocial. Ressalta-se a necessidade de uma gestão comprometida com a qualidade da assistência em face do risco de suicídio.

RESUMEN Objetivo Comprender las implicaciones de la asistencia brindada a las personas con conducta suicida dentro del alcance de la Red de Atención Psicosocial, desde la perspectiva de los usuarios y profesionales de la salud. Método Investigación cualitativa, bajo el marco teórico del pensamiento complejo y metodológico en la Grounded Theory. Se realizaron entrevistas, de mayo a diciembre de 2017, com usuarios asistidos por conducta suicida y con profesionales de la salud en entornos de atención psicosocial. Se utilizó la técnica de análisis de datos comparativos. Resultados Participaron 18 usuarios y 15 profesionales de La salud. La no recepción intensifica la introspección, la desmotivación y la desesperanza de los usuarios, lo que aumenta la dificultad de exponer sus deseos. En situaciones de recepción, la disponibilidad y la vinculación con profesionales, se sienten más abiertos, hasta el punto de dar nuevos significados a la vida y reducir los pensamientos de muerte. Conclusión Se notaron debilidades y potencialidades en la atención brindada por profesionales de la salud a usuarios con conducta suicida, dentro del alcance de la Red de Atención Psicosocial. Destaca la necesidad de una gestión comprometida con la calidad de la atención ante el riesgo de suicidio.

ABSTRACT Objective To understand the implications of the assistance provided to people with suicidal behavior within the scope of the Psychosocial Care Network, from the perspective of users and health professionals. Method A qualitative research, under the theoretical framework of complex and methodological thinking in Grounded Theory. Interviews were conducted from May to December 2017, with users assisted due to suicidal behavior and with health professionals in psychosocial care settings. The comparative data analysis technique was used Results 18 users and health professionals participated. Non-acceptance intensifies users' introspection, demotivation and hopelessness, increasing the difficulty of exposing their desires. In situations of embracement, availability and bonding with professionals, patients feel more open, to the point of giving new meanings to life and reducing thoughts of death. Conclusion Weaknesses and potentialities were noticed in the care provided by health professionals to users with suicidal behavior, within the scope of the Psychosocial Care Network. The need for management committed to the quality of care in the face of the risk of suicide stands out.

Child and adolescent violence: oral story of women who attempted suicide / Violencia en la infancia y adolescencia: historia oral de mujeres que intentaron suicidio / Violência na infância e adolescência: história oral de mulheres que tentaram suicídio

ABSTRACT Objective: To unveil expressions of intrafamily violence experienced in childhood and/or adolescence by women who attempted suicide. Method: This is a study with a qualitative approach based on Oral Story. Participants were ten women with a history of suicide attempt, who experienced intrafamily violence in childhood and/or adolescence. The research was carried out at the Center for the Study and Prevention of Suicide, linked to a Toxicological Information Center in the city of Salvador, Bahia, Brazil. Results: From the orality of women, the study allowed the emergence of the following representative categories of intrafamily abuse experienced in childhood and/or adolescence: psychological violence, rejection, neglect, physical violence and sexual violence. Final considerations: The study alerts to intrafamily violence as an aggravation related to suicidal behavior, offering elements that help in the identification of their expressions, which will raise awareness to suicidal behavior and consequently suicide prevention.

RESUMEN Objetivo: Desvelar las expresiones de la violencia intrafamiliar vivenciadas en la infancia y/o adolescencia por mujeres que intentaron suicidio. Método: Se trata de un estudio con enfoque cualitativo, fundamentado en la Historia Oral. Participaron diez mujeres con historia de intento de suicidio, que experimentaron violencia intrafamiliar en la infancia y/o adolescencia. La investigación fue realizada en el Núcleo de Estudo e Prevenção do Suicídio (Núcleo de Estudio y Prevención del Suicidio), vinculado a un Centro de Información Toxicológica en la ciudad de Salvador, Bahía, Brasil. Resultados: A partir de la oralidad de las mujeres, el estudio permitió emerger las siguientes categorías representativas de la expresión de abuso intrafamiliar vivenciada en la niñez y/o adolescencia: violencia psicológica (rechazo y negligencia), violencia física y violencia sexual. Consideraciones finales: El estudio alerta sobre la violencia intrafamiliar como agravio relacionado al comportamiento suicida, ofreciendo elementos que auxilian en la identificación de sus expresiones, lo que posibilitará atención para el comportamiento suicida y consecuentemente la prevención del suicidio.

RESUMO Objetivo: Desvelar as expressões da violência intrafamiliar vivenciadas na infância e/ou adolescência por mulheres que tentaram suicídio. Método: Trata-se de um estudo com abordagem qualitativa, fundamentada na História Oral. Participaram dez mulheres com história de tentativa de suicídio, que experienciaram violência intrafamiliar na infância e/ou adolescência. A pesquisa foi realizada no Núcleo de Estudo e Prevenção do Suicídio, vinculado a um Centro de Informação Toxicológica na cidade de Salvador, Bahia, Brasil. Resultados: A partir da oralidade das mulheres, o estudo permitiu emergir as seguintes categorias representativas da expressão de abuso intrafamiliar vivenciada na infância e/ou adolescência: violência psicológica (rejeição, negligência), violência física e violência sexual. Considerações finais: O estudo alerta para a violência intrafamiliar enquanto agravo relacionado ao comportamento suicida, oferecendo elementos que auxiliam na identificação de suas expressões, o que possibilitará atenção para o comportamento suicida e consequentemente prevenção do suicídio.

Child and adolescent violence: oral story of women who attempted suicide.

OBJECTIVE: To unveil expressions of intrafamily violence experienced in childhood and/or adolescence by women who attempted suicide. METHOD: This is a study with a qualitative approach based on Oral Story. Participants were ten women with a history of suicide attempt, who experienced intrafamily violence in childhood and/or adolescence. The research was carried out at the Center for the Study and Prevention of Suicide, linked to a Toxicological Information Center in the city of Salvador, Bahia, Brazil. RESULTS: From the orality of women, the study allowed the emergence of the following representative categories of intrafamily abuse experienced in childhood and/or adolescence: psychological violence, rejection, neglect, physical violence and sexual violence. FINAL CONSIDERATIONS: The study alerts to intrafamily violence as an aggravation related to suicidal behavior, offering elements that help in the identification of their expressions, which will raise awareness to suicidal behavior and consequently suicide prevention.

Suporte social de familiares e amigos: discurso de pessoas com comportamento suicida / Apoyo social de familiares y amigos: discurso de personas con comportamiento suicida / Social support from family and friends: discourse of people with suicidal behavior

RESUMO Objetivo: identificar os elementos que favorecem o suporte social de familiares e amigos às pessoas com comportamento suicida. Método: trata-se de uma pesquisa qualitativa, desenvolvida com 18 pessoas em acompanhamento terapêutico no Núcleo de Estudo e Prevenção do Suicídio, Salvador, Bahia, Brasil. Os dados foram coletados de março a agosto de 2018 e organizados com base no Discurso do Sujeito Coletivo. Resultados: o estudo evidenciou que o vínculo afetivo, a experiência prévia de sofrimento psíquico, a empatia e a compreensão acerca do comportamento suicida constituem elementos que refletem suporte social importante por parte de familiares e amigos. Considerações Finais: o conhecimento e a utilização desses elementos poderão subsidiar ações para a prevenção do suicídio, uma vez que os profissionais de saúde ao cuidar das pessoas com comportamento suicida podem desenvolver estratégias que visem ao fortalecimento do suporte social.

RESUMEN Objetivo: identificar los elementos que favorecen el apoyo social de familiares y amigos a las personas con comportamiento suicida. Método: investigación cualitativa, desarrollada con 18 personas en acompañamiento terapéutico en el Núcleo de Estudio y Prevención del Suicidio, en Salvador, Bahia, Brasil. Se obtuvieron los datos de marzo a agosto de 2018 y estos se los organizaron con base en el Discurso del Sujeto Colectivo. Resultados: el estudio evidenció que el vínculo afectivo, la experiencia previa de sufrimiento psíquico, la empatía y la compresión acerca del comportamiento suicida constituyen elementos que revelan apoyo social importante por los familiares y amigos. Conclusión: el conocimiento y la utilización de esos elementos podrán subsidiar acciones para la prevención del suicidio, ya que, al cuidar de personas con comportamiento suicida, los profesionales de salud pueden desarrollar estrategias para fortalecer el apoyo social.

ABSTRACT Objective: To identify the elements that favor the social support from family and friends to people with suicidal behavior. Method: Qualitative study with 18 individuals undergoing therapeutic follow-up in the Center for Suicide Research and Prevention (NEPS) of Salvador, Bahia, Brazil. Data was collected from March to August 2018 and organized based on the Collective Subject Discourse methodology. Results: The study showed that affectional bonds, previous experiences of mental suffering, empathy and understanding of suicidal behavior are elements that reflect significant social support from family and friends. Final Considerations: Knowledge and use of these elements may support actions for the prevention of suicide, since health professionals responsible for care to people with suicidal behavior may develop strategies aimed at strengthening social support.

Sinais de risco para o suicídio em mulheres com história de violência doméstica* / Signs of suicide risk in women with a history of domestic violence / Signos de riesgo para el suicidio en mujeres con antecedentes de violencia doméstica

OBJETIVO: identificar sinais de risco para o suicídio em mulheres com história de violência doméstica. MÉTODO: estudo exploratório-descritivo, com abordagem qualitativa. Participaram dez mulheres com história de violência doméstica e tentativa de suicídio por envenenamento. A pesquisa foi realizada no Núcleo de Estudo e Prevenção do Suicídio, vinculado a um Centro de Informação Toxicológica, em Salvador, Bahia, Brasil. RESULTADOS: sinaliza para a relação entre a vivência de violência doméstica e o comprometimento para a saúde mental, representado por Comportamento depressivo e Comportamento suicida. CONCLUSÃO: o estudo revelou comportamentos que consistem em sinais de alerta para o risco de suicídio, ao tempo em que oferece subsídios para a promoção de estratégias de cuidado às mulheres com história de violência doméstica.

OBJECTIVE: to analyze the meaning of the use and abuse of alcohol and / or other drugs among university students in accordance with Brazilian public policy on drugs. METHODS: 49 university students from a Public Institution of Higher Education in the Southeast region of Brazil participated. RESULTS: Bardin's Content Analysis elaborated the analytical category: "Dissonance between public policies and the meaning of drug use among university students". Drug use and abuse begin in adolescence; Stimulated by family and friends, and refers to the happiness and flight of problems. CONCLUSION: it is fundamental to know the meaning of drug use and abuse, from the perspective of the university for the elaboration and implementation of public policies.

OBJETIVO: identificar signos de riesgo para el suicidio en mujeres con historia de violencia doméstica. MÉTODO: estudio exploratorio-descriptivo, con abordaje cualitativo Participaron diez mujeres con historia de violencia doméstica e intento de suicidio por envenenamiento. La investigación fue realizada en el Núcleo de Estudio y Prevención del Suicidio, vinculado a un Centro de Información Toxicológica, en Salvador, Bahia, Brasil. RESULTADOS: señala para la relación entre la vivencia de violencia doméstica y el compromiso para la salud mental, representado por: Comportamiento depresivo y Comportamiento suicida. CONCLUSIONES: el estudio reveló comportamientos que consisten en señales de alerta para el riesgo de suicidio, al tiempo que ofrece subsidios para la promoción de estrategias de cuidado a las mujeres con historia de violencia doméstica.

Human leukemia mutations corrupt but do not abrogate GATA-2 function.

By inducing the generation and function of hematopoietic stem and progenitor cells, the master regulator of hematopoiesis GATA-2 controls the production of all blood cell types. Heterozygous GATA2 mutations cause immunodeficiency, myelodysplastic syndrome, and acute myeloid leukemia. GATA2 disease mutations commonly disrupt amino acid residues that mediate DNA binding or cis-elements within a vital GATA2 intronic enhancer, suggesting a haploinsufficiency mechanism of pathogenesis. Mutations also occur in GATA2 coding regions distinct from the DNA-binding carboxyl-terminal zinc finger (C-finger), including the amino-terminal zinc finger (N-finger), and N-finger function is not established. Whether distinct mutations differentially impact GATA-2 mechanisms is unknown. Here, we demonstrate that N-finger mutations decreased GATA-2 chromatin occupancy and attenuated target gene regulation. We developed a genetic complementation assay to quantify GATA-2 function in myeloid progenitor cells from Gata2 -77 enhancer-mutant mice. GATA-2 complementation increased erythroid and myeloid differentiation. While GATA-2 disease mutants were not competent to induce erythroid differentiation of Lin-Kit+ myeloid progenitors, unexpectedly, they promoted myeloid differentiation and proliferation. As the myelopoiesis-promoting activity of GATA-2 mutants exceeded that of GATA-2, GATA2 disease mutations are not strictly inhibitory. Thus, we propose that the haploinsufficiency paradigm does not fully explain GATA-2-linked pathogenesis, and an amalgamation of qualitative and quantitative defects instigated by GATA2 mutations underlies the complex phenotypes of GATA-2-dependent pathologies.

Triagem auditiva neonatal com emissão otoacústica transiente utilizando estímulo de banda estreita / Neonatal hearing screening with transient evoked otoacoustic emissions using narrow band stimulus

OBJETIVO: avaliar a sensibilidade e a especificidade de um equipamento automático de Emissão Otoacustica Evocada Transiente que utiliza um estímulo de banda estreita, Narrow. MÉTODOS: foi analisado o resultado da Triagem Auditiva Neonatal de 300 neonatos. A Emissão Otoacústica Evocada Transiente foi realizada com um equipamento portátil automático, com o estímulo de banda estreita - Narrow. Todos os neonatos foram submetidos ao Potencial Evocado Auditivo de Tronco Encefálico com o estímulo clique, duração 100μs como padrão-ouro. RESULTADOS: o percentual de "passa" na Triagem Auditiva Neonatal foi de 90,7%. Considerando os resultados do padrão-ouro, foi observado uma taxa de falso-positivo de 9%. A sensibilidade e especificidade encontradas foram de 100% e 92%, respectivamente. CONCLUSÃO: o estímulo de banda estreita - Narrow mostrou-se eficaz para ser utilizado nos programa de Triagem Auditiva Neonatal Universal. .

PURPOSE: to assess the sensitivity and specificity of an automated Transient Evoked Otoacoustic Emissions equipment using narrow band stimulus. METHODS: the hearing screening results of 300 newborns were analyzed. A portable automated equipment was used with narrow band stimulus to conduct the Transient Evoked Otoacoustic Emissions. All newborns were also submitted to the Brainstem Auditory Evoked Potentials using 100μs-duration click stimuli, which was considered the gold standard test. RESULTS: the proportion of "pass" results in the neonatal hearing screening was 90.7%. Considering the gold standard results, it was observed a false-positive rate of 9%. The Transient Evoked Otoacoustic Emissions with narrow band stimulus presented sensitivity of 100% and specificity of 92%. CONCLUSION: the narrow band stimulus was efficient enough to be used in neonatal hearing screening programs. .

Epigenetic Determinants of Erythropoiesis: Role of the Histone Methyltransferase SetD8 in Promoting Erythroid Cell Maturation and Survival.

Erythropoiesis, in which committed progenitor cells generate millions of erythrocytes daily, involves dramatic changes in the chromatin structure and transcriptome of erythroblasts, prior to their enucleation. While the involvement of the master-regulatory transcription factors GATA binding protein 1 (GATA-1) and GATA-2 in this process is established, the mechanistic contributions of many chromatin-modifying/remodeling enzymes in red cell biology remain enigmatic. We demonstrated that SetD8, a histone methyltransferase that catalyzes monomethylation of histone H4 at lysine 20 (H4K20me1), is a context-dependent GATA-1 corepressor in erythroid cells. To determine whether SetD8 controls erythroid maturation and/or function, we used a small hairpin RNA (shRNA)-based loss-of-function strategy in a primary murine erythroblast culture system. In this system, SetD8 promoted erythroblast maturation and survival, and this did not involve upregulation of the established regulator of erythroblast survival Bcl-x(L). SetD8 catalyzed H4K20me1 at a critical Gata2 cis element and restricted occupancy by an enhancer of Gata2 transcription, Scl/TAL1, thereby repressing Gata2 transcription. Elevating GATA-2 levels in erythroid precursors yielded a maturation block comparable to that induced by SetD8 downregulation. As lowering GATA-2 expression in the context of SetD8 knockdown did not rescue erythroid maturation, we propose that SetD8 regulation of erythroid maturation involves multiple target genes. These results establish SetD8 as a determinant of erythroid cell maturation and provide a framework for understanding how a broadly expressed histone-modifying enzyme mediates cell-type-specific GATA factor function.