Reprogramming Cancer Cells to Antigen-presenting Cells.

Cancer cells evade the immune system by downregulating antigen presentation. Although immune checkpoint inhibitors (ICI) and adoptive T-cell therapies revolutionized cancer treatment, their efficacy relies on the intrinsic immunogenicity of tumor cells and antigen presentation by dendritic cells. Here, we describe a protocol to directly reprogram murine and human cancer cells into tumor-antigen-presenting cells (tumor-APCs), using the type 1 conventional dendritic cell (cDC1) transcription factors PU.1, IRF8, and BATF3 delivered by a lentiviral vector. Tumor-APCs acquire a cDC1 cell-like phenotype, transcriptional and epigenetic programs, and function within nine days (Zimmermannova et al., 2023). Tumor-APCs express the hematopoietic marker CD45 and acquire the antigen presentation complexes MHC class I and II as well as co-stimulatory molecules required for antigen presentation to T cells, but do not express high levels of negative immune checkpoint regulators. Enriched tumor-APCs present antigens to Naïve CD8+ and CD4+ T cells, are targeted by activated cytotoxic T lymphocytes, and elicit anti-tumor responses in vivo. The tumor-APC reprogramming protocol described here provides a simple and robust method to revert tumor evasion mechanisms by increasing antigen presentation in cancer cells. This platform has the potential to prime antigen-specific T-cell expansion, which can be leveraged for developing new cancer vaccines, neoantigen discovery, and expansion of tumor-infiltrating lymphocytes. Key features • This protocol describes the generation of antigen-presenting cells from cancer cells by direct reprogramming using lineage-instructive transcription factors of conventional dendritic cells type I. • Verification of reprogramming efficiency by flow cytometry and functional assessment of tumor-APCs by antigen presentation assays.

GATA2 mitotic bookmarking is required for definitive haematopoiesis.

In mitosis, most transcription factors detach from chromatin, but some are retained and bookmark genomic sites. Mitotic bookmarking has been implicated in lineage inheritance, pluripotency and reprogramming. However, the biological significance of this mechanism in vivo remains unclear. Here, we address mitotic retention of the hemogenic factors GATA2, GFI1B and FOS during haematopoietic specification. We show that GATA2 remains bound to chromatin throughout mitosis, in contrast to GFI1B and FOS, via C-terminal zinc finger-mediated DNA binding. GATA2 bookmarks a subset of its interphase targets that are co-enriched for RUNX1 and other regulators of definitive haematopoiesis. Remarkably, homozygous mice harbouring the cyclin B1 mitosis degradation domain upstream Gata2 partially phenocopy knockout mice. Degradation of GATA2 at mitotic exit abolishes definitive haematopoiesis at aorta-gonad-mesonephros, placenta and foetal liver, but does not impair yolk sac haematopoiesis. Our findings implicate GATA2-mediated mitotic bookmarking as critical for definitive haematopoiesis and highlight a dependency on bookmarkers for lineage commitment.

Prone position effect in intensive care patients with SARS-COV-2 pneumonia.

Ventilation in the prone position (PP) has been used for decades in patients with acute respiratory distress syndrome (ARDS) and is associated with a reduction in mortality rate. Its application has been extended to patients with SARS-Cov-2 pneumonia and is recommended by the main international organizations. The objective is to evaluate the effects of PP on the outcomes of patients with SARS-Cov-2 pneumonia admitted to a multipurpose intensive care unit. This is a quantitative, quasi-experimental, single-group, longitudinal and retrospective study. Data were collected based on clinical records. Data were processed using SPSS (version 26.0). PP significantly increased oxygenation in patients with SARS-Cov-2 pneumonia, with a mean increase of 21.27% between the PaO2/FiO2 ratio before and after the PP. However, its effectiveness was inversely proportional to the number of cycles performed and the timing of orotracheal intubation. PP improves oxygenation in patients with SARS-Cov-2 pneumonia. However, multiple PP sessions are not beneficial, as this procedure is no longer effective after the fourth cycle. This study thus contributes to better management in the approach of critically ill patients with SARS-Cov-2 pneumonia.

Restoring tumor immunogenicity with dendritic cell reprogramming.

Decreased antigen presentation contributes to the ability of cancer cells to evade the immune system. We used the minimal gene regulatory network of type 1 conventional dendritic cells (cDC1) to reprogram cancer cells into professional antigen-presenting cells (tumor-APCs). Enforced expression of the transcription factors PU.1, IRF8, and BATF3 (PIB) was sufficient to induce the cDC1 phenotype in 36 cell lines derived from human and mouse hematological and solid tumors. Within 9 days of reprogramming, tumor-APCs acquired transcriptional and epigenetic programs associated with cDC1 cells. Reprogramming restored the expression of antigen presentation complexes and costimulatory molecules on the surfaces of tumor cells, allowing the presentation of endogenous tumor antigens on MHC-I and facilitating targeted killing by CD8+ T cells. Functionally, tumor-APCs engulfed and processed proteins and dead cells, secreted inflammatory cytokines, and cross-presented antigens to naïve CD8+ T cells. Human primary tumor cells could also be reprogrammed to increase their capability to present antigen and to activate patient-specific tumor-infiltrating lymphocytes. In addition to acquiring improved antigen presentation, tumor-APCs had impaired tumorigenicity in vitro and in vivo. Injection of in vitro generated melanoma-derived tumor-APCs into subcutaneous melanoma tumors delayed tumor growth and increased survival in mice. Antitumor immunity elicited by tumor-APCs was synergistic with immune checkpoint inhibitors. Our approach serves as a platform for the development of immunotherapies that endow cancer cells with the capability to process and present endogenous tumor antigens.

Essential Oils Encapsulated in Zeolite Structures as Delivery Systems (EODS): An Overview.

Essential oils (EO) obtained from plants have proven industrial applications in the manufacturing of perfumes and cosmetics, in the production and flavoring of foods and beverages, as therapeutic agents in aromatherapy, and as the active principles or excipients of medicines and pharmaceutics due to their olfactory, physical-chemical, and biological characteristics. On behalf of the new paradigm of a more natural and sustainable lifestyle, EO are rather appealing due to their physical, chemical, and physiological actions in human beings. However, EO are unstable and susceptible to degradation or loss. To tackle this aspect, the encapsulation of EO in microporous structures as zeolites is an attractive solution, since these host materials are cheap and non-toxic to biological environments. This overview provides basic information regarding essential oils, including their recognized benefits and functional properties. Current progress regarding EO encapsulation in zeolite structures is also discussed, highlighting some representative examples of essential oil delivery systems (EODS) based on zeolites for healthcare applications or aromatherapy.

Single-cell transcriptional profiling informs efficient reprogramming of human somatic cells to cross-presenting dendritic cells.

Type 1 conventional dendritic cells (cDC1s) are rare immune cells critical for the induction of antigen-specific cytotoxic CD8+ T cells, although the genetic program driving human cDC1 specification remains largely unexplored. We previously identified PU.1, IRF8, and BATF3 transcription factors as sufficient to induce cDC1 fate in mouse fibroblasts, but reprogramming of human somatic cells was limited by low efficiency. Here, we investigated single-cell transcriptional dynamics during human cDC1 reprogramming. Human induced cDC1s (hiDC1s) generated from embryonic fibroblasts gradually acquired a global cDC1 transcriptional profile and expressed antigen presentation signatures, whereas other DC subsets were not induced at the single-cell level during the reprogramming process. We extracted gene modules associated with successful reprogramming and identified inflammatory signaling and the cDC1-inducing transcription factor network as key drivers of the process. Combining IFN-γ, IFN-ß, and TNF-α with constitutive expression of cDC1-inducing transcription factors led to improvement of reprogramming efficiency by 190-fold. hiDC1s engulfed dead cells, secreted inflammatory cytokines, and performed antigen cross-presentation, key cDC1 functions. This approach allowed efficient hiDC1 generation from adult fibroblasts and mesenchymal stromal cells. Mechanistically, PU.1 showed dominant and independent chromatin targeting at early phases of reprogramming, recruiting IRF8 and BATF3 to shared binding sites. The cooperative binding at open enhancers and promoters led to silencing of fibroblast genes and activation of a cDC1 program. These findings provide mechanistic insights into human cDC1 specification and reprogramming and represent a platform for generating patient-tailored cDC1s, a long-sought DC subset for vaccination strategies in cancer immunotherapy.

Long-term Efficacy and Safety of Everolimus Versus Mycophenolate in Kidney Transplant Recipients Receiving Tacrolimus.

BACKGROUND: The short-term efficacy and safety of everolimus in combination with tacrolimus have been described in several clinical trials. Yet, detailed long-term data comparing the use of everolimus or mycophenolate in kidney transplant recipients receiving tacrolimus are lacking. METHODS: This is a 5-y follow-up post hoc analysis of a prospective trial including 288 patients who were randomized to receive a single 3-mg/kg dose of rabbit antithymocyte globulin, tacrolimus, everolimus (EVR), and prednisone (rabbit antithymocyte globulin/EVR, n = 85); basiliximab, tacrolimus, everolimus, and prednisone (basiliximab/EVR, n = 102); or basiliximab, tacrolimus, mycophenolate, and prednisone (basiliximab/mycophenolate, n = 101). RESULTS: There were no differences in the incidence of treatment failure (31.8% versus 40.2% versus 34.7%, P = 0.468), de novo donor-specific HLA antibodies (6.5% versus 11.7% versus 4.0%, P = 0.185), patient (92.9% versus 94.1% versus 92.1%, P = 0.854), and death-censored graft (87.1% versus 90.2% versus 85.1%, P = 0.498) survivals. Using a sensitive analysis, the trajectories of estimated glomerular filtration rate were comparable in the intention-to-treat (P = 0.145) and per protocol (P = 0.354) populations. There were no differences in study drug discontinuation rate (22.4% versus 30.4% versus 17.8%, P = 0.103). CONCLUSIONS: In summary, this analysis in a cohort of de novo low/moderate immunologic risk kidney transplant recipients suggests that the use of a single 3 mg/kg rabbit antithymocyte globulin dose followed by EVR combined with reduced tacrolimus concentrations was associated with similar efficacy and renal function compared with the standard of care immunosuppressive regimen.

Cell Fate Reprogramming in the Era of Cancer Immunotherapy.

Advances in understanding how cancer cells interact with the immune system allowed the development of immunotherapeutic strategies, harnessing patients' immune system to fight cancer. Dendritic cell-based vaccines are being explored to reactivate anti-tumor adaptive immunity. Immune checkpoint inhibitors and chimeric antigen receptor T-cells (CAR T) were however the main approaches that catapulted the therapeutic success of immunotherapy. Despite their success across a broad range of human cancers, many challenges remain for basic understanding and clinical progress as only a minority of patients benefit from immunotherapy. In addition, cellular immunotherapies face important limitations imposed by the availability and quality of immune cells isolated from donors. Cell fate reprogramming is offering interesting alternatives to meet these challenges. Induced pluripotent stem cell (iPSC) technology not only enables studying immune cell specification but also serves as a platform for the differentiation of a myriad of clinically useful immune cells including T-cells, NK cells, or monocytes at scale. Moreover, the utilization of iPSCs allows introduction of genetic modifications and generation of T/NK cells with enhanced anti-tumor properties. Immune cells, such as macrophages and dendritic cells, can also be generated by direct cellular reprogramming employing lineage-specific master regulators bypassing the pluripotent stage. Thus, the cellular reprogramming toolbox is now providing the means to address the potential of patient-tailored immune cell types for cancer immunotherapy. In parallel, development of viral vectors for gene delivery has opened the door for in vivo reprogramming in regenerative medicine, an elegant strategy circumventing the current limitations of in vitro cell manipulation. An analogous paradigm has been recently developed in cancer immunotherapy by the generation of CAR T-cells in vivo. These new ideas on endogenous reprogramming, cross-fertilized from the fields of regenerative medicine and gene therapy, are opening exciting avenues for direct modulation of immune or tumor cells in situ, widening our strategies to remove cancer immunotherapy roadblocks. Here, we review current strategies for cancer immunotherapy, summarize technologies for generation of immune cells by cell fate reprogramming as well as highlight the future potential of inducing these unique cell identities in vivo, providing new and exciting tools for the fast-paced field of cancer immunotherapy.

A Multidisciplinary Fingerprinting Approach for Authenticity and Geographical Traceability of Portuguese Wines.

The interest in developing reliable wine authenticity schemes is a hot-topic, especially for wines with recognized added-value. In order to accomplish this goal, two dimensions need to be considered: the grapevine variety determination and the geographical provenance. The aim of this study was to develop a multidisciplinary approach applicable to wines from the sub region Melgaço and Monção of the demarcated Vinho Verde region and from the demarcated Douro region. The proposed scheme consists on the use of DNA-based assays to detect Single Nucleotide Polymorphisms (SNPs) on three genes of the anthocyanin pathway (UFGT, F3H and LDOX) coupled with High-resolution melting (HRM) analysis aiming the varietal identification. The Alvarinho wines revealed to have the same haplotype using this marker set, demonstrating its applicability for genetic identification. In addition, to assess their geographical provenance, a multi-elemental approach using Sr and Pb isotopic ratios of wine, soil and bedrock samples was used. The isotopic data suggest a relation between Sr and Pb uptake by vine roots and soil's texture and clay content, rather than with the whole rock's isotopic ratios, but also highlights the potential of a discriminating method based on the combination of selected isotopic signatures.

Mortalidade por suicídio em adolescentes, adultos e idosos, nas regiões do Brasil, entre 1996 e 2016 / Suicide mortality in adolescents, adults and older adults, in the regions of Brazil, between 1996 and 2016

Objetivo: Verificar a tendência da taxa de mortalidade por suicídio em adolescentes, adultos e idosos, nas Regiões do Brasil, entre 1996 e 2016. Métodos: Estudo de séries temporais, incluindo óbitos por suicídio de adolescentes, adultos e idosos. Foram utilizados dados secundários, disponibilizados pelo Sistema de Informação de Mortalidade e pelo Instituto Brasileiro de Geografia e Estatística. A análise de regressão linear segmentada foi adotada para calcular a variação anual percentual e alterações significativas na tendência. Resultados: Entre 1996 e 2016 ocorreram 195.440 óbitos por suicídio no Brasil. Houve aumento significativo na taxa de mortalidade por suicídio na região Nordeste em adolescentes e adultos do sexo feminino. As taxas aumentaram no Nordeste e reduziram significativamente no Sudeste e Sul para as idosas. O sexo masculino apresentou aumento da taxa de mortalidade por suicídio nas regiões Norte, Nordeste e CentroOeste para os adolescentes; aumento nas regiões Norte e Nordeste e, redução significativa da taxa na região Sul para os adultos. Para os idosos, houve aumento na região Norte e redução significativa da taxa na região Sul. Conclusão: Observou-se diferentes taxas de mortalidade por suicídio entre regiões, sexos e grupos etários.

Role of nurses for continuity of care after hospital discharge / Papel do enfermeiro para a continuidade do cuidado na alta hospitalar / Rol enfermero para continuidad del cuidado en el alta hospitalaria

ABSTRACT Objective: to recognize the role of nurses to maintain continuity of care for users after hospital discharge. Method: an exploratory, descriptive study with a qualitative approach. The study was applied at hospital discharge originating from the most complex health center in Magallanes, the Hospital Clinico Magallanes, Chile. Data were collected through interviews with nurses, carried out between May and August 2018. To analyze the material, the content analysis technique was used. Results: three categories emerged, which bring together what nurses mention in their discourse: How they see the implementation of hospital nursing services, which facilitate continuity of care in the healthcare network of discharged patients (known as care networks); Who they identify in the nursing service for continuity of care after discharge (care networks), which these nursing professionals make and suggestions for their performance; and How care networks affect users in continuity of care after discharge. Conclusion: the role of nurses is key in patient discharge from hospital. With autonomy and competencies for comprehensive care, professionals facilitate the healthcare transition; manage hospital discharge, convening the institutional nursing network and the emerging networks with primary health care; aspire to develop strategies for an inter-level care network, with systematic participation.

RESUMO Objetivo: reconhecer o papel do enfermeiro em manter a continuidade do cuidado do usuário com a alta hospitalar. Método: estudo descritivo, exploratório, com abordagem qualitativa. O estudo foi aplicado na alta hospitalar, originária da unidade de saúde mais complexa de Magallanes, o Hospital Clinico de Magallanes, Chile. Os dados foram coletados por meio de entrevistas com enfermeiros, realizadas entre maio e agosto de 2018. Para a análise do material, foi utilizada a técnica de análise de conteúdo. Resultados: foram obtidas três categorias, que reúnem as expressões dos enfermeiros: Como vêem a implantação dos serviços de enfermagem hospitalar, que facilitam a continuidade do cuidado na rede de atenção do paciente com alta hospitalar (denominada rede de atenção); Quem eles identificam no serviço de enfermagem para a continuidade dos cuidados pós-alta (redes de atenção), que esses profissionais de enfermagem fazem e sugestões para seu desempenho; e, Como as redes de atendimento afetam o usuário na continuidade de seus cuidados pós-alta. Conclusão: o papel da enfermagem é fundamental na alta hospitalar do paciente. Com autonomia e competências para o cuidado integral, o profissional facilita a transição da assistência à saúde; gerencia a alta hospitalar, convocando a rede institucional de enfermagem e as redes emergentes com a atenção primária à saúde; aspira a desenvolver estratégias para uma rede de atenção inter-nível, com participação sistemática.

RESUMEN Objetivo: reconocer rol enfermero para mantener la continuidad del cuidado del usuario con alta hospitalaria. Método: estudio de carácter exploratorio, descriptivo, con abordaje cualitativo. El estudio se aplicó en el alta hospitalaria, que se origina en el centro de salud de mayor complejidad de Magallanes, el Hospital Clínico de Magallanes, Chile. Los datos fueron recolectados a través de entrevistas con enfermeras, que se realizaron entre mayo y agosto de 2018. Para el análisis del material, se utilizó la técnica análisis de contenido. Resultados: se obtienen tres categorías, que reúnen lo que los enfermeros mencionan en su discurso: Como ven la implementación de servicios de enfermería hospitalaria, que facilitan continuidad de la atención en la red asistencial del paciente con alta hospitalaria (conocido como redes de cuidado); A quiénes identifican en el servicio de enfermería para la continuidad de la atención post alta (redes de cuidado), que hacen estos profesionales de enfermería y sugerencias para su desempeño; y Como redes de cuidado afectan al usuario en la continuidad de su cuidado post alta. Conclusión: el rol enfermero es clave en el alta hospitalaria del paciente. Con autonomía y competencias para la atención integral, el profesional facilita la transición asistencial; gestiona el alta hospitalaria, convocando la red de enfermería institucional y las incipientes redes con Atención Primaria de Salud; aspira a desarrollar estrategias para una red de cuidado interniveles, con participación sistemica.

Trabalho noturno e alterações de peso corporal autopercebidas pelos profissionais de enfermagem / Night work and self-perceived body weight changes among nursing professionals / Trabajo nocturno y alteraciones en el peso corporal según los trabajadores de enfermería

Objetivo: avaliar as alterações de peso corporal em trabalhadores de enfermagem do turno noturno. Metodologia: estudo quantitativo, exploratório, descritivo, realizado em um hospital federal de grande porte do Rio de Janeiro. Foram estudadas variáveis sóciodemográficas; influências do turno noturno sobre o organismo e índice de massa corporal, após aprovação do Comitê de Ética em Pesquisa da instituição. Resultados: os 89 trabalhadores de enfermagem apresentaram ganho de peso médio de aproximadamente 20Kg a partir da admissão no turno noturno, sendo que os enfermeiros referiram maior influência da ausência de sono sobre o organismo, e maior exaustão quando comparados aos dados das demais categorias. Conclusão: considerando as desordens hormonais e os impactos sociais do serviço noturno, é imprescindível a implementação de mudanças para uma cultura prevencionista, seja por programas institucionais ou pesquisas intervencionistas, capazes de desenvolver medidas que conduzam ao autorreconhecimento e à promoção do bem-estar físico, mental e social dos trabalhadores de enfermagem.

Objective: to evaluate body weight changes in nursing workers on the night shift. Methodology: this quantitative, exploratory, descriptive study, conducted at a large federal hospital in Rio de Janeiro, after approval of the institution's research ethics committee, considered socio-demographic variables, influence of the night work on the organism, and body mass index. Results: average weight gain among the 89 nursing workers was approximately 20kg since admission to night work, and nurses reported greater influence of lack of sleep on the body, and greater exhaustion as compared with data on the other categories. Conclusion: considering the hormonal disorders and social impacts of night work, it is essential to implement changes towards a culture of prevention, through either institutional programs or interventionist research able to develop measures that lead to self-recognition and promotion of nursing workers' physical, mental and social wellbeing.

Objetivo: evaluar las alteraciones de peso corporal en trabajadores de enfermería del turno nocturno. Metodología: estudio cuantitativo, exploratorio, descriptivo, realizado en un gran hospital federal en Río de Janeiro. Se estudiaron las variables sociodemográficas, la influencia reportada de la guardia nocturna en el organismo y el índice de masa corporal, tras la aprobación del Comité de Ética de Investigación de la Institución. Resultados: Los 89 trabajadores de enfermería tuvieron un aumento de peso promedio de aproximadamente 20 kg desde el ingreso en el turno nocturno, y los enfermeros informaron una mayor influencia de la falta de horas dormidas sobre el cuerpo y un mayor agotamiento en comparación con los datos de las otras categorías. Conclusión: Teniendo en cuenta los trastornos hormonales y los impactos sociales del servicio nocturno, es esencial implementar cambios hacia una cultura de prevención, ya sea a través de programas institucionales o de investigación intervencionista, capaces de desarrollar medidas que conduzcan al auto reconocimiento y a la promoción del bienestar físico, mentales y social de los trabajadores de enfermería.

Prospective randomized study comparing everolimus and mycophenolate sodium in de novo kidney transplant recipients from expanded criteria deceased donor.

The optimal immunosuppressive regimen for recipients of expanded criteria donor (ECD) kidneys has not been identified. In this single-center study, 171 recipients of ECD kidney transplants were randomized to receive antithymocyte globulin induction, and delayed introduction of reduced dose tacrolimus, prednisone and everolimus (r-ATG/EVR, n = 88), or mycophenolate (r-ATG/MPS, n = 83). No cytomegalovirus (CMV) pharmacological prophylaxis was used. The primary endpoint was the incidence of CMV infection/disease at 12 months. Secondary endpoints included treatment failure [first biopsy-proven acute rejection (BPAR), graft loss, or death] and safety. Patients treated with EVR showed a 89% risk reduction (13.6 vs. 71.6%; HR 0.11, 95% CI 0.06-0.220, P < 0.001) in the incidence of first CMV infection/disease. Incidences of BPAR (16% vs. 5%, P = 0.021), graft loss (11% vs. 1%, P = 0.008), death (10% vs. 1%, P = 0.013), and treatment discontinuation (40% vs. 28%, P = 0.12) were higher in the r-ATG/EVR, leading to premature study termination. Mean glomerular filtration rate was lower in r-ATG/EVR (31.8 ± 18.8 vs. 42.6 ± 14.9, P < 0.001). In recipients of ECD kidney transplants receiving no CMV pharmacological prophylaxis, the use of everolimus was associated with higher treatment failure compared with mycophenolate despite the significant reduction in the incidence of CMV infection/disease (ClinicalTrials.gov.NCT01895049).

Incidence and risk factors associated with cytomegalovirus infection after the treatment of acute rejection during the first year in kidney transplant recipients receiving preemptive therapy.

INTRODUCTION: The complex interaction between cytomegalovirus (CMV) infection and acute rejection after kidney transplantation is well recognized. METHODS: This single center retrospective cohort analysis investigated the incidence and risk factors associated with CMV infection after treatment for acute rejection (tAR) in kidney transplant recipients receiving only CMV preemptive therapy. Of the 938 kidney transplants performed between 04/30/2014 and 04/30/2015 we identified 87 (9.3%) that were treated for acute rejection within the first year. RESULTS: Most patients (64%) received rATG induction therapy followed by tacrolimus in combination with azathioprine (67%) or mycophenolate (33%) and corticosteroids. The incidence of CMV infection/disease after tAR was 47%, of which 73% occurred within 30 days. Using multivariable logistic regression analysis, eGFR at 1 month (OR = 0.98; 95% CI, 0.97-0.99; P = 0.007) and timing of tAR (OR = 0.98; 95% CI, 0.96-0.99; P = 0.021) were independently associated with CMV infection/disease after tAR. CONCLUSION: In this cohort of kidney transplant recipients receiving tacrolimus-based immunosuppressive and preemptive CMV therapy, almost 50% developed CMV infection/disease after tARin the first year of transplantation. Early rejection and poor initial renal function were risk factors associated with CMV infection or disease.

Configuração da gestão do cuidado de Enfermagem no Brasil: uma análise documental / Configuration of the management of Nursing care in Brazil: a documentary analysis

Objetivo: configurar a gestão do cuidado de enfermagem, segundo as Resoluções do Conselho Federal de Enfermagem. Metodologia: estudo qualitativo, de natureza exploratório-descritiva, do tipo documental, com fonte de dados na legislação do Conselho Federal de Enfermagem, de 1975 a 2017. As Resoluções foram organizadas em tabelas do Microsoft Word e analisadas no software MaxQDA®. Resultados: com base nas Resoluções do Conselho Federal de Enfermagem, os resultados deste estudo mostraram que o enfermeiro é o profissional que atua como gestor do cuidado de enfermagem. Dentre as 33 Resoluções que atenderam aos critérios de inclusão, identificaram-se e analisaram-se três categorias: atribuições privativas para o gerenciamento de enfermagem; deveres e obrigações do enfermeiro no âmbito gerencial e a autonomia profissional para a prática gerencial. Conclusão: o enfermeiro possui atividades privativas, autonomia profissional, deveres e obrigações e vedações diretamente relacionadas à sua atuação no gerenciamento dos serviços e cuidados de enfermagem.

Objective: to configure the management of nursing care, according to the Resolutions of the Federal Nursing Council. Methodology: a qualitative, exploratory-descriptive, documentary type study whose data source constituted the Council’s legislation Federal University of Nursing, from 1975 to 2017, available on its website. The Resolutions were organized into Microsoft Word tables and analyzed in MaxQDA® software. Results: based on the Resolutions of the Federal Nursing Council, the results of this study showed that the nurse is the professional who acts as nurse care manager. Among the 33 Resolutions that met the inclusion criteria, three categories were identified and analyzed: private assignments for nursing management; duties and obligations in the managerial scope and the professional autonomy for the managerial practice. Conclusion: the nurse has private activities, professional autonomy, duties and obligations and prohibitions directly related to their performance in the management of services and nursing care.

Meta: configurar la gestión del cuidado de enfermería, según las Resoluciones del Consejo Federal de Enfermería. Metodología: estudio cualitativo, de naturaleza exploratorio-descriptiva, del tipo documental, con fuente de datos en la legislación del Consejo Federal de Enfermería, de 1975 a 2017. Las Resoluciones fueron organizadas en tablas de Microsoft Word y analizadas en el software MaxQDA®. Resultados: Los resultados de este estúdio mostraron que El enfermero es el profesional que actúa como gestor del cuidado de enfermería. Entre las 33 Resoluciones que atendieron a los criterios de inclusión, se identificaron y analizaron tres categorías: atribuciones privativas para el manejo de enfermería; deberes y obligaciones del enfermero em el ámbito gerencial y la autonomia profesional para la práctica gerencial. Conclusión: el enfermero posee actividades privativas, autonomía profesional, deberes y obligaciones y vedaciones directamente relacionadas a su actuación en la gestión de los servicios y cuidados de enfermería.

Evitabilidade do óbito infantil e fetal: interlocução entre comitê e atenção primária à saúde / Evitabilidad del óbito infantil y fetal: diálogo entre comité y atención básica a la salud / Avoidance of infant and fetal death: interlocution between the committee and primary health care

RESUMO Objetivo: evidenciar como ocorre a interlocução entre o Comitê de Prevenção do Óbito Materno, Infantil e Fetal e a Atenção Primária à Saúde no município de Florianópolis, Santa Catarina. Método: estudo de caso único, com abordagem qualitativa, que teve como contexto o referido Comitê, justificado pelo caso decisivo, o Distrito Sanitário Norte. Na coleta de dados foram utilizadas quatro fontes de evidência e, na análise, a técnica de construção da explanação. Resultados: evidenciou-se a implantação e organização do Grupo Técnico de Estudos sobre Mortalidade Materno-Infantil, como o agente interlocutor entre o Comitê e a atenção primária, que revisa condutas e processos de trabalho e propõe melhorias na assistência durante o pré-natal. Conclusão: as estratégias de gestão implementadas pelo Distrito Norte podem ser tomadas como exemplo para outros cenários, sobretudo para a promoção de uma interlocução efetiva com a atenção primária.

RESUMEN: Objetivo: evidenciar cómo ocurre el diálogo entre el Comité de Prevención del Óbito Materno, Infantil y Fetal y la Atención Básica a la Salud en el municipio de Florianópolis, Santa Catarina. Método: estudio de caso único, con abordaje cualitativo, que tuvo como contexto el antedicho Comité, justificado por el caso decisivo, el Distrito Sanitario Norte. En la obtención de datos se utilizaron cuatro fuentes de evidencia y, en el análisis, la técnica de construcción de la explanación. Resultados: se evidenciaron la implantación y la organización del Grupo Técnico de Estudios sobre Mortalidad Materno Infantil, como el agente de diálogo entre el Comité y la atención básica, que revisa conductas y procesos de trabajo y propone mejorías en la asistencia durante el prenatal. Conclusión: las estrategias de gestión implementadas por el Distrito Norte pueden ser ejemplo para otros escenarios, sobre todo para la promoción de una interlocución efectiva con la atención básica.

ABSTRACT Objective: to investigate how the interlocution between the Committee for the Prevention of Maternal, Infant and Fetal Death and Primary Health Care takes place in the municipality of Florianópolis, Santa Catarina. Method: a single case study, with a qualitative approach, which had the Committee mentioned as the context, justified by the decisive case of the Northern Health District. ,Four sources of evidence were used in the data collection and the explanatory construction technique in the analysis,. Results: the implantation and organization of the Mother and Infant Mortality Study Technical Group was highlighted, this being the interlocutor agent between the Committee and primary care, which reviews behaviors and work processes and proposes improvements in prenatal care. Conclusion: the management strategies implemented by the Northern District can be taken as an example for other scenarios, especially for the promotion of an effective interlocution with primary care.

Direct reprogramming of fibroblasts into antigen-presenting dendritic cells.

Ectopic expression of transcription factors has been used to reprogram differentiated somatic cells toward pluripotency or to directly reprogram them to other somatic cell lineages. This concept has been explored in the context of regenerative medicine. Here, we set out to generate dendritic cells (DCs) capable of presenting antigens from mouse and human fibroblasts. By screening combinations of 18 transcription factors that are expressed in DCs, we have identified PU.1, IRF8, and BATF3 transcription factors as being sufficient to reprogram both mouse and human fibroblasts to induced DCs (iDCs). iDCs acquire a conventional DC type 1-like transcriptional program, with features of interferon-induced maturation. iDCs secrete inflammatory cytokines and have the ability to engulf, process, and present antigens to T cells. Furthermore, we demonstrate that murine iDCs generated here were able to cross-present antigens to CD8+ T cells. Our reprogramming system should facilitate better understanding of DC specification programs and serve as a platform for the development of patient-specific DCs for immunotherapy.

The influence of clinical, environmental, and socioeconomic factors on five-year patient survival after kidney transplantation.

INTRODUCTION: The risk of death after kidney transplant is associated with the age of the recipient, presence of comorbidities, socioeconomic status, local environmental characteristics and access to health care. OBJECTIVE: To investigate the causes and risk factors associated with death during the first 5 years after kidney transplantation. METHODS: This was a single-center, retrospective, matched case-control study. RESULTS: Using a consecutive cohort of 1,873 kidney transplant recipients from January 1st 2007 to December 31st 2009, there were 162 deaths (case group), corresponding to 5-year patient survival of 91.4%. Of these deaths, 25% occurred during the first 3 months after transplant. The most prevalent cause of death was infectious (53%) followed by cardiovascular (24%). Risk factors associated with death were history of diabetes, dialysis type and time, unemployment, delayed graft function, number of visits to center, number of hospitalizations, and duration of hospital stay. After multivariate analysis, only time on dialysis, number of visits to center, and days in hospital were still associated with death. Patients who died had a non-significant higher number of treated acute rejection episodes (38% vs. 29%, p = 0.078), higher mean number of adverse events per patient (5.1 ± 3.8 vs. 3.8 ± 2.9, p = 0.194), and lower mean eGFR at 3 months (50.8 ± 25.1 vs. 56.7 ± 20.7, p = 0.137) and 48 months (45.9 ± 23.8 vs. 58.5 ± 20.2, p = 0.368). CONCLUSION: This analysis confirmed that in this population, infection is the leading cause of mortality over the first 5 years after kidney transplantation. Several demographic and socioeconomic risk factors were associated with death, most of which are not readily modifiable.