Spatiotemporal dynamics of cytokines expression dictate fetal liver hematopoiesis.

During embryogenesis, yolk-sac and intra-embryonic-derived hematopoietic progenitors, comprising the precursors of adult hematopoietic stem cells, converge into the fetal liver. With a new staining strategy, we defined all non-hematopoietic components of the fetal liver and found that hepatoblasts are the major producers of hematopoietic growth factors. We identified mesothelial cells, a novel component of the stromal compartment, producing Kit ligand, a major hematopoietic cytokine. A high-definition imaging dataset analyzed using a deep-learning based pipeline allowed the unambiguous identification of hematopoietic and stromal populations, and enabled determining a neighboring network composition, at the single cell resolution. Throughout active hematopoiesis, progenitors preferentially associate with hepatoblasts, but not with stellate or endothelial cells. We found that, unlike yolk sac-derived progenitors, intra-embryonic progenitors respond to a chemokine gradient created by CXCL12-producing stellate cells. These results revealed that FL hematopoiesis is a spatiotemporal dynamic process, defined by an environment characterized by low cytokine concentrations.

Assembling the layers of the hematopoietic system: A window of opportunity for thymopoiesis in the embryo.

During embryonic development, several independent generations of hematopoietic cells were identified. They occur in the yolk sac and the intra-embryonic major arteries, in a narrow window of development. They arise sequentially, starting with primitive erythrocytes in the yolk sac blood islands, progressing to less differentiated erythromyeloid progenitors still in the yolk sac, and culminating with multipotent progenitors, some of which will generate the adult hematopoietic stem cell compartment. All these cells contribute to the formation of a layered hematopoietic system that reflects adaptative strategies to the fetal environment and the embryo's needs. It is mostly composed, at these stages, of erythrocytes and tissue-resident macrophages both of yolk sac origin, the latter persisting throughout life. We propose that subsets of lymphocytes of embryonic origin derive from a different intra-embryonic generation of multipotent cells occurring before the emergence of hematopoietic stem cell progenitors. These multipotent cells have a limited lifespan and generate cells that provide basic protection against pathogens before the adaptive immune system is functional, contribute to tissue development and homeostasis, and shape the establishment of a functional thymus. Understanding the properties of these cells will impact the understanding of childhood leukemia and of adult autoimmune pathology and thymic involution.

Identification of fetal liver stroma in spectral cytometry using the parameter autofluorescence.

The fetal liver (FL) is the main hematopoietic organ during embryonic development. The FL is also the unique anatomical site where hematopoietic stem cells expand before colonizing the bone marrow, where they ensure life-long blood cell production and become mostly resting. The identification of the different cell types that comprise the hematopoietic stroma in the FL is essential to understand the signals required for the expansion and differentiation of the hematopoietic stem cells. We used a panel of monoclonal antibodies to identify FL stromal cells in a 5-laser equipped spectral flow cytometry (FCM) analyzer. The "Autofluorescence Finder" of SONY ID7000 software identified two distinct autofluorescence emission spectra. Using autofluorescence as a fluorescence parameter we could assign the two autofluorescent signals to three distinct cell types and identified surface markers that characterize these populations. We found that one autofluorescent population corresponds to hepatoblast-like cells and cholangiocytes whereas the other expresses mesenchymal transcripts and was identified as stellate cells. Importantly, after birth, autofluorescence becomes the unique identifying property of hepatoblast-like cells because mature cholangiocytes are no longer autofluorescent. These results show that autofluorescence used as a parameter in spectral FCM is a useful tool to identify new cell subsets that are difficult to analyze in conventional FCM.

Application of Optimal Control of Infectious Diseases in a Model-Free Scenario.

Optimal control for infectious diseases has received increasing attention over the past few decades. In general, a combination of cost state variables and control effort have been applied as cost indices. Many important results have been reported. Nevertheless, it seems that the interpretation of the optimal control law for an epidemic system has received less attention. In this paper, we have applied Pontryagin's maximum principle to develop an optimal control law to minimize the number of infected individuals and the vaccination rate. We have adopted the compartmental model SIR to test our technique. We have shown that the proposed control law can give some insights to develop a control strategy in a model-free scenario. Numerical examples show a reduction of 50% in the number of infected individuals when compared with constant vaccination. There is not always a prior knowledge of the number of susceptible, infected, and recovered individuals required to formulate and solve the optimal control problem. In a model-free scenario, a strategy based on the analytic function is proposed, where prior knowledge of the scenario is not necessary. This insight can also be useful after the development of a vaccine to COVID-19, since it shows that a fast and general cover of vaccine worldwide can minimize the number of infected, and consequently the number of deaths. The considered approach is capable of eradicating the disease faster than a constant vaccination control method.

Crosstalk Between the Hepatic and Hematopoietic Systems During Embryonic Development.

Hematopoietic stem cells (HSCs) generated during embryonic development are able to maintain hematopoiesis for the lifetime, producing all mature blood lineages. HSC transplantation is a widely used cell therapy intervention in the treatment of hematologic, autoimmune and genetic disorders. Its use, however, is hampered by the inability to expand HSCs ex vivo, urging for a better understanding of the mechanisms regulating their physiological expansion. In the adult, HSCs reside in the bone marrow, in specific microenvironments that support stem cell maintenance and differentiation. Conversely, while developing, HSCs are transiently present in the fetal liver, the major hematopoietic site in the embryo, where they expand. Deeper insights on the dynamics of fetal liver composition along development, and on how these different cell types impact hematopoiesis, are needed. Both, the hematopoietic and hepatic fetal systems have been extensively studied, albeit independently. This review aims to explore their concurrent establishment and evaluate to what degree they may cross modulate their respective development. As insights on the molecular networks that govern physiological HSC expansion accumulate, it is foreseeable that strategies to enhance HSC proliferation will be improved.

Hematopoiesis: A Layered Organization Across Chordate Species.

The identification of distinct waves of progenitors during development, each corresponding to a specific time, space, and function, provided the basis for the concept of a "layered" organization in development. The concept of a layered hematopoiesis was established by classical embryology studies in birds and amphibians. Recent progress in generating reliable lineage tracing models together with transcriptional and proteomic analyses in single cells revealed that, also in mammals, the hematopoietic system evolves in successive waves of progenitors with distinct properties and fate. During embryogenesis, sequential waves of hematopoietic progenitors emerge at different anatomic sites, generating specific cell types with distinct functions and tissue homing capacities. The first progenitors originate in the yolk sac before the emergence of hematopoietic stem cells, some giving rise to progenies that persist throughout life. Hematopoietic stem cell-derived cells that protect organisms against environmental pathogens follow the same sequential strategy, with subsets of lymphoid cells being only produced during embryonic development. Growing evidence indicates that fetal immune cells contribute to the proper development of the organs they seed and later ensure life-long tissue homeostasis and immune protection. They include macrophages, mast cells, some γδ T cells, B-1 B cells, and innate lymphoid cells, which have "non-redundant" functions, and early perturbations in their development or function affect immunity in the adult. These observations challenged the view that all hematopoietic cells found in the adult result from constant and monotonous production from bone marrow-resident hematopoietic stem cells. In this review, we evaluate evidence for a layered hematopoietic system across species. We discuss mechanisms and selective pressures leading to the temporal generation of different cell types. We elaborate on the consequences of disturbing fetal immune cells on tissue homeostasis and immune development later in life.

Gerenciamento de segurança do cuidado do paciente em cenário hospitalar: produção de vídeo educativo para prevenção e notificação de eventos adversos / Patient care safety management in a hospital setting: educational video production for adverse event prevention and reporting

Esta pesquisa de mestrado destaca o ambiente temático pertencente ao segmento de Segurança em Saúde em Enfermagem. Sobretudo, o intuito na eleição deste tema foi a vontade de aprofundamento do assunto no processo de notificação dos eventos adversos no cuidado do paciente em cenário hospitalar. Objetivos: estruturar vídeo educativo contendo orientações para o registro de notificações de eventos adversos no sistema informatizado adotado na instituição de saúde; identificar os indicadores de monitoramento de processos e de notificação de eventos adversos; mapear os resultados do monitoramento dos indicadores de processos e de notificação; avaliar o registro dos eventos adversos e os fatores associados às ações de cuidado. Metodologia: trata-se de uma pesquisa avaliativa do tipo metodológico com o desenvolvimento de um vídeo educativo. Neste estudo, foram levantados e mapeados os indicadores de monitoramento de processos e de notificação de eventos adversos. Com base na análise desses indicadores e dos problemas identificados nos processos de notificação e nas diretrizes das Seis Metas Internacionais de Segurança do Paciente da OMS, presentes nos Protocolos de Segurança do Paciente, procedeu-se com a etapa de desenvolvimento do vídeo educativo. Resultados: de modo geral, os motivos das notificações se relacionaram mais a queixas técnicas do que propriamente a registros de incidentes. A relação entre os eventos adversos e as metas de segurança acompanhou o padrão de classificação identificado para os incidentes em geral, uma vez que a maioria se apresentou como Não estabelecidos pela JCI/OMS. Conclusão: considera-se que avanços no cenário atual das organizações de saúde seja desafiador, uma vez que constituem ambientes complexos onde a ocorrência de incidentes deriva de um conjunto de fatores que envolvem desde as práticas dos profissionais aos produtos e processos instituídos na unidade. Diante do exposto, o estudo tem papel importante já que oferece subsídios informativos para a melhora na relação dos profissionais de saúde com o paciente, evitando possíveis situações de risco, além de estimular a prática da notificação de incidentes

This master's research highlights the thematic environment belonging to the Health Safety in Nursing segment. Above all, the intention of this theme election was the desire to deepen the subject in the process of adverse events notification in the care of patients in a hospital setting. Objectives: structure educational film containing guidelines for the registration of adverse event notifications in the computerized system adopted at the health institution; identify the process monitoring and adverse event notification indicators; map the results of the monitoring of the process and notification indicators; evaluate the registry of adverse events and the factors associated with care actions. Methodology: this is an evaluation research of the methodological type with the development of an educational film. In this study, the indicators of process monitoring and adverse event notification were raised and mapped. Based on the analysis of these indicators and the problems identified in the notification processes and the guidelines of the Six International Patient Safety Goals of WHO, presented in the Patient Safety Protocols, the educational video development stage was carried out. Results: In general, the reasons for notifications related more to technical complaints than to incident records. The relationship between adverse events and the safety goals followed the classification pattern identified for incidents in general, since most were presented as Not established by JCI/WHO. Conclusion: it is considered that advances in the current scenario of health organizations are challenging, since they are complex environments where the occurrence of incidents derives from a set of factors that involve from the practices of the professionals to the products and processes instituted in the unit. In view of the above, the study has an important role since it provides informational subsidies for improving the relationship between health professionals and patients, avoiding possible risk situations, and encouraging the practice of incident reporting

Esta investigación de maestría destaca el ambiente temático perteneciente al segmento de Seguridad en Salud en Enfermería. Sobre todo, la intención en la elección de este tema fue la voluntad de profundizar el asunto en el proceso de notificación de los eventos adversos en el cuidado del paciente en un escenario hospitalario. Objetivos: estructurar película educativa que contenga orientaciones para el registro de notificaciones de eventos adversos en el sistema informatizado adoptado en la institución de salud; identificar los indicadores de monitoreo de procesos y de notificación de eventos adversos; mapear los resultados del monitoreo de los indicadores de procesos y de notificación; evaluar el registro de los eventos adversos y los factores asociados a las acciones de cuidado. Metodología: se trata de una investigación de evaluación del tipo metodológico con el desarrollo de una película educativa. En este estudio, fueron levantados y mapeados los indicadores de monitoreo de procesos y de notificación de eventos adversos. Con base en el análisis de estos indicadores y de los problemas identificados en los procesos de notificación y en las directrices de las seis metas internacionales de seguridad del paciente de la OMS presentes en los protocolos de seguridad del paciente, se procedió con la etapa de desarrollo del video educativo. Resultados: En general, los motivos de las notificaciones se relacionaron más con quejas técnicas que a los registros de incidentes. La relación entre los eventos adversos y las metas de seguridad acompañó el patrón de clasificación identificado para los incidentes en general, ya que la mayoría se presentó como No establecidos por la JCI/OMS. Conclusión: se considera que avances en el escenario actual de las organizaciones de salud es desafiante, ya que constituyen ambientes complejos donde la ocurrencia de incidentes deriva de un conjunto de factores que involucran desde las prácticas de los profesionales a los productos y procesos instituidos en la unidad. Ante lo expuesto, el estudio tiene un papel importante ya que ofrece subsidios informativos para la mejora en la relación de los profesionales de la salud con el paciente, evitando posibles situaciones de riesgo, además de estimular la práctica de la notificación de incidentes

CPAP increases 6-minute walk distance after lung resection surgery.

BACKGROUND: The application of CPAP has been used to minimize postoperative pulmonary complications after lung resection surgery. The aim of this study was to quantify both the CPAP effects upon lung function and functional capacity in early postoperative lung resection, as well as to evaluate if CPAP prolongs air leak through the chest drain. METHODS: Thirty patients in the postoperative period of lung resection were allocated into 2 groups: an experimental group, consisting of 15 patients who underwent a 10 cm H(2)O CPAP, and a 15 patient control group, who performed breathing exercises. Arterial blood gas analysis, peak expiratory flow (PEF), respiratory muscle strength, spirometry, and 6-min walk test (6MWT) were assessed in the preoperative period, and repeated postoperatively on the first and on the seventh day (6MWT was repeated only on the seventh day). RESULTS: Significant increases in PEF, muscle strength, and FEV(1) between the first and seventh postoperative day were observed, both in the experimental and in the control group, whereas FVC and P(aO(2)) increased significantly between the first and seventh postoperative day only in the experimental group. The average loss in 6-min walk distance (6MWD) from preoperative to postoperative day 7 in the experimental group was significantly lower than in control group. When comparing the 2 groups, only 6MWD was statistically different (P < .001). There was no air leakage increase through the drain with the early use of CPAP. CONCLUSION: When compared to breathing exercises, CPAP increases the 6MWD in postoperative lung resection patients, without prolonging air leak through the chest drain.