The role of time in involving patients with cancer in treatment decision making: A scoping review.

BACKGROUND: Time is often perceived as a barrier to shared decision making in cancer care. It remains unclear how time functions as a barrier and how it could be most effectively utilized. OBJECTIVE: This scoping review aimed to describe the role of time in patient involvement, and identify strategies to overcome time-related barriers. METHODS: Seven databases were searched for any publications on patient involvement in cancer treatment decisions, focusing on how time is used to involve patients, the association between time and patient involvement, and/or strategies to overcome time-related barriers. Reviewers worked independently and in duplicate to select publications and extract data. One coder thematically analyzed data, a second coder checked these analyses. RESULTS: The analysis of 26 eligible publications revealed four themes. Time was a resource 1) to process the diagnosis, 2) to obtain/process/consider information, 3) for patients and clinicians to spend together, and 4) for patient involvement in making decisions. DISCUSSION: Time is a resource throughout the treatment decision-making process, and generic strategies have been proposed to overcome time constraints. PRACTICE VALUE: Clinicians could co-create decision-making timelines with patients, spread decisions across several consultations, share written information with patients, and support healthcare redesigns that allocate the necessary time.

Maternal mortality: protocol of a study integrated to the Birth in Brazil II survey. / Mortalidade materna: protocolo de um estudo integrado à pesquisa Nascer no Brasil II.

The Maternal Mortality Study conducts a hospital investigation of maternal deaths that occurred in 2020/2021 in the maternity hospitals sampled by the Birth in Brazil II survey, with the following objectives: estimate the maternal mortality underreporting; calculate a correction factor and the corrected (MMR); validate the causes of maternal mortality reported in the death certificate (DC); and analyze the factors associated with maternal mortality. The Birth in Brazil II includes approximately 24,250 puerperal women distributed in 465 public, private, and mixed hospitals with ≥ 100 live births/year in the five macroregions of Brazil. The Maternal Mortality Study data will be completed using the same Birth in Brazil II questionnaire, from the consultation of hospital records. Trained obstetricians will fill out a new DC (redone DC) from independent analysis of this questionnaire, comparing it to official data. The database of the investigated deaths will be related to the deaths listed in the Mortality Information System of the Brazilian Ministry of Health, allowing the estimation of underreporting and calculation of the corrected MMR. To calculate the reliability of the causes of death, the kappa test and prevalence-adjusted kappa with 95% confidence interval will be used. A case-control study to estimate the risk factors for maternal mortality will be developed with the investigated deaths (cases) and the controls obtained in the Birth in Brazil II survey, using conditional multiple logistic regression models. We expect this research to contribute to the correction of the underreporting of maternal mortality and to a better understanding of the determinants of the persistence of a high MMR in Brazil.

O Estudo da Mortalidade Materna conduz uma investigação hospitalar dos óbitos maternos ocorridos em 2020/2021 nas maternidades amostradas na pesquisa Nascer no Brasil II, com os seguintes objetivos: estimar o sub-registro da mortalidade materna e calcular um fator de correção e a razão de mortalidade materna (RMM) corrigida; validar as causas de mortalidade materna informadas na declaração de óbito (DO); e analisar os fatores associados à mortalidade materna. O Nascer no Brasil II inclui aproximadamente 24.255 puérperas distribuídas em 465 hospitais públicos, privados e mistos com ≥ 100 partos de nascidos vivos/ano nas cinco macrorregiões do país. Os dados do Estudo da Mortalidade Materna serão preenchidos utilizando o mesmo questionário do Nascer no Brasil II, a partir da consulta aos prontuários hospitalares. Obstetras treinados preencherão uma nova DO (DO refeita) a partir de análise independente desse questionário, comparando aos dados oficiais. A base de dados dos óbitos investigados será relacionada com os óbitos constantes no Sistema de Informações sobre Mortalidade do Ministério da Saúde, permitindo a estimativa do sub-registro e cálculo da RMM corrigida. Para o cálculo da confiabilidade das causas de morte, serão utilizados os testes kappa e kappa ajustado à prevalência com intervalo de 95% de confiança. Um estudo de caso-controle para estimar os fatores de risco para mortalidade materna será desenvolvido com os óbitos investigados (casos) e os controles obtidos na pesquisa Nascer no Brasil II, utilizando-se modelos de regressão logística múltipla condicional. Espera-se contribuir para a correção do sub-registro da mortalidade materna e para a melhor compreensão dos fatores determinantes da persistência de RMM elevada no Brasil.

El Estudio de Mortalidad Materna evalúa las muertes maternas ocurridas en 2020-2021 en las muestras de maternidades del encuesta Nacer en Brasil II con los objetivos de estimar el subregistro de mortalidad materna y calcular el factor de corrección y la tasa de mortalidad materna corregida (TMM); validar las causas de mortalidad materna reportadas en el certificado de defunción (CD); y analizar los factores asociados a la mortalidad materna. La Nacer en Brasil II incluye aproximadamente 24.250 mujeres puerperales, distribuidas en 465 hospitales públicos, privados y mixtos con ≥ 100 nacidos vivos/año en las cinco macrorregiones de Brasil. Los datos de Estudio de Mortalidad Materna se completarán con la información del cuestionario Nacer en Brasil II a partir de una búsqueda de los registros médicos hospitalarios. Los obstetras capacitados completarán un nuevo CD (CD rehecho) desde un análisis independiente de este cuestionario, comparándolo con los datos oficiales. La base de datos de muertes investigadas se relacionará con las muertes que constan en el Sistema de Informaciones sobre la Mortalidad del Ministerio de Salud para permitir la estimación del subregistro y el cálculo de la TMM corregida. Para calcular la exactitud de las causas de muerte, se utilizarán las pruebas kappa y kappa ajustada a la prevalencia con un intervalo de 95% de confianza. Un estudio de casos y controles se aplicará para estimar los factores de riesgo de las mortalidad materna con las muertes investigadas (casos) y los controles obtenidos en el estudio Nacer en Brasil II utilizando modelos de regresión logística múltiple condicional. Se espera que este estudio pueda contribuir a la corrección del subregistro de la mortalidad materna y a una mejor comprensión de los determinantes de la persistencia de alta TMM en Brasil.

Perinatal mortality, severe maternal morbidity and maternal near miss: protocol of a study integrated with the Birth in Brazil II survey. / Mortalidade perinatal, morbidade materna grave e near miss materno: protocolo de um estudo integrado à pesquisa Nascer no Brasil II.

Brazil presents high maternal and perinatal morbidity and mortality. Cases of severe maternal morbidity, maternal near miss, and perinatal deaths are important health indicators and share the same determinants, being closely related to living conditions and quality of perinatal care. This article aims to present the study protocol to estimate the perinatal mortality rate and the incidence of severe maternal morbidity and maternal near miss in the country, identifying its determinants. Cross-sectional study integrated into the research Birth in Brazil II, conducted from 2021 to 2023. This study will include 155 public, mixed and private maternities, accounting for more than 2,750 births per year, participating in the Birth in Brazil II survey. We will collect retrospective data from maternal and neonatal records of all hospitalizations within a 30-day period in these maternities, applying a screening form to identify cases of maternal morbidity and perinatal deaths. Medical record data of all identified cases will be collected after hospital discharge, using a standardized instrument. Cases of severe maternal morbidity and maternal near miss will be classified based on the definition adopted by the World Health Organization. The perinatal deaths rate and the incidence of severe maternal morbidity and maternal near miss will be estimated. Cases will be compared to controls obtained in the Birth in Brazil II survey, matched by hospital and duration of pregnancy, in order to identify factors associated with negative outcomes. Results are expected to contribute to the knowledge on maternal morbidity and perinatal deaths in Brazil, as well as the development of strategies to improve care.

O Brasil apresenta elevada morbimortalidade materna e perinatal. Casos de morbidade materna grave, near miss materno e óbitos perinatais são indicadores importantes de saúde e compartilham dos mesmos determinantes sociais, tendo estreita relação com as condições de vida e qualidade da assistência perinatal. Este artigo pretende apresentar o protocolo de estudo que visa estimar a taxa de mortalidade perinatal e a incidência de morbidade materna grave e near miss materno no país, assim como identificar seus determinantes. Trata-se de estudo transversal integrado à pesquisa Nascer no Brasil II, realizada entre 2021 e 2023. Serão incluídas neste estudo 155 maternidades públicas, mistas e privadas, com mais de 2.750 partos por ano, participantes do Nascer no Brasil II. Nessas maternidades, será realizada coleta retrospectiva de dados de prontuário materno e neonatal de todas as internações ocorridas num período de 30 dias, com aplicação de uma ficha de triagem para identificação de casos de morbidade materna e de óbito perinatal. Dados de prontuário de todos os casos identificados serão coletados após a alta hospitalar, utilizando instrumento padronizado. Casos de morbidade materna grave e near miss materno serão classificados por meio da definição adotada pela Organização Mundial da Saúde. Será estimada a taxa de mortalidade perinatal e a incidência de morbidade materna grave e near miss materno. Os casos serão comparados a controles obtidos na pesquisa Nascer no Brasil II, pareados por hospital e duração da gestação, visando a identificação de fatores associados aos desfechos negativos. Espera-se que os resultados deste artigo contribuam para o conhecimento sobre a morbidade materna e a mortalidade perinatal no país, bem como para a elaboração de estratégias de melhoria do cuidado.

Brasil tiene una alta morbimortalidad materna y perinatal. Los casos de morbilidad materna severa, maternal near miss y muertes perinatales son importantes indicadores de salud y comparten los mismos determinantes sociales, y tienen una estrecha relación con las condiciones de vida y la calidad de la asistencia perinatal. Este artículo pretende presentar el protocolo de estudio que tiene como objetivo estimar la tasa de mortalidad perinatal y la incidencia de morbilidad materna severa y maternal near miss en el país, así como identificar sus determinantes. Se trata de un estudio transversal integrado a la investigación Nacer en Brasil II, realizada entre el 2021 y el 2023. Este estudio incluirá 155 maternidades públicas, mixtas y privadas, con más de 2.750 partos al año, que participan en el Nacer en Brasil II. En estas maternidades, se realizará una recopilación retrospectiva de datos de las historias clínicas maternas y neonatales de todas las hospitalizaciones ocurridas en un período de 30 días, con la aplicación de un formulario de triaje para identificar casos de morbilidad materna y de muerte perinatal. Los datos de las historias clínicas de todos los casos identificados se recopilarán tras el alta hospitalaria, mediante un instrumento estandarizado. Los casos de morbilidad materna severa y maternal near miss se clasificarán por medio de la definición adoptada por la Organización Mundial de la Salud. Se estimará la tasa de mortalidad perinatal y la incidencia de morbilidad materna severa y maternal near miss. Los casos se compararán con los controles obtenidos en el estudio Nacer en Brasil II, emparejados por hospital y duración del embarazo, para identificar factores asociados con desenlaces negativos. Se espera que los resultados de este artículo contribuyan al conocimiento sobre la morbilidad materna y la mortalidad perinatal en el país, así como a la elaboración de estrategias para mejorar el cuidado.

Health care itineraries for women in situations of abortion: methodological aspects of a qualitative study for Birth in Brazil II survey. / Itinerários de cuidado à saúde de mulheres em situações de abortamento: aspectos metodológicos do estudo qualitativo da pesquisa Nascer no Brasil II.

In recent decades, several academic studies on abortion have been produced in Brazil, with different designs, objectives, and methodologies. However, due to the diversity of situations in which Brazilian women experience abortion, the complexity of this topic, and its modulations in different political and sociocultural contexts, it still challenges academicians and the fields of health and reproductive rights. In this article, we present methodological aspects of a qualitative study on health care itineraries of women in situations of abortion, a component of the Birth in Brazil II survey, whose objective is to discuss the effects of gender; race/ethnicity; social class; generational, regional, and territorial inequalities on care itineraries. We discuss the study design development, the construction of the theoretical framework and specific analytical axes, the development of interview instrument, definition of participant selection criteria, strategies to contact participants and conduct the interviews, management of field work and materials produced, analytical procedures, and ethical issues. In total, 120 narrative interviews were conducted in order to include a diversity of women and obtain detailed results from the quantitative analysis under Birth in Brazil II survey. The context of criminalization of abortion has an impact on the production of knowledge on this subject, creating challenges such as difficult access to women, women's anonymity, privacy and data confidentiality, creation of objective and subjective conditions so that they can narrate their experiences in depth. With this article, we seek to contribute to the debate about these challenges in abortion research in Brazil.

Nas últimas décadas, produziu-se um robusto corpus de pesquisas sobre aborto no Brasil, com diferentes desenhos, objetos e metodologias. Contudo, pela diversidade de situações em que as mulheres brasileiras vivenciam o abortamento, pela complexidade do tema e por suas modulações em contextos políticos e socioculturais distintos, o assunto não cessa de desafiar a academia, o campo da saúde e dos direitos reprodutivos. Neste artigo, apresentamos aspectos metodológicos de um estudo qualitativo sobre itinerários de cuidado à saúde de mulheres em situações de abortamento, componente da pesquisa Nascer no Brasil II, que objetiva discutir efeitos das desigualdades de gênero, de raça/etnia, de classe social, geracionais, regionais e territoriais nesses percursos. Discutimos o desenvolvimento do desenho do estudo; a construção do arcabouço teórico e recortes analíticos específicos; a elaboração do instrumento de entrevista; os critérios de seleção das mulheres; as estratégias de abordagem e condução das entrevistas; a gestão do fluxo do campo e dos materiais produzidos; os procedimentos analíticos; e os problemas éticos. Para incluir uma diversidade de mulheres e aprofundar resultados do componente quantitativo do Nascer no Brasil II, serão realizadas 120 entrevistas narrativas. O contexto de criminalização do aborto impacta a produção de conhecimento sobre o tema, impondo desafios como conseguir acesso às mulheres, assegurar o anonimato e sua privacidade, além do sigilo das informações, gerar condições objetivas e subjetivas para que possam narrar em profundidade as suas experiências. Com este artigo, procuramos contribuir para o debate sobre esses desafios das pesquisas sobre aborto no Brasil.

En las últimas décadas, se produjo un robusto corpus de investigaciones sobre el aborto en Brasil, con diferentes diseños, objetos y metodologías. Sin embargo, debido a la diversidad de situaciones en las que las mujeres brasileñas vivencian el abortamiento, la complejidad del tema y sus modulaciones en diferentes contextos políticos y socioculturales, el tema continúa desafiando a la academia, el campo de la salud y los derechos reproductivos. En este artículo, presentamos aspectos metodológicos de un estudio cualitativo sobre los itinerarios de cuidados de la salud de mujeres en situación de abortamiento, componente de la encuesta Nacer en Brasil II, que tiene como objetivo discutir los efectos de las desigualdades de género, raza/etnia, clase social, generacionales, regionales y territoriales en esos recorridos. Discutimos el desarrollo del diseño del estudio, la construcción del marco teórico y los recortes analíticos específicos, la elaboración del instrumento de entrevista, los criterios de selección de las mujeres, las estrategias de abordaje y realización de las entrevistas, el manejo del flujo del campo y de los materiales producidos, los procedimientos analíticos y los problemas éticos. Para abarcar una diversidad de mujeres y profundizar los resultados del componente cuantitativo de Nacer en Brasil II, se realizarán 120 entrevistas narrativas. El contexto de criminalización del aborto impacta la producción de conocimiento sobre el tema, imponiendo desafíos, tales como conseguir acceso a las mujeres, asegurar su anonimato y privacidad y la confidencialidad de la información, generar condiciones objetivas y subjetivas para que puedan narrar en profundidad sus experiencias. Con este artículo buscamos contribuir al debate sobre estos desafíos de las investigaciones sobre el aborto en Brasil.

Birth in Brazil II: a postpartum maternal, paternal and child health research protocol. / Nascer no Brasil II: protocolo de investigação da saúde materna, paterna e da criança no pós-parto.

Pregnancy, parturition and birth bring major changes to the lives of mothers and fathers. This article presents a research protocol for estimating the prevalence of postpartum mental health outcomes in mothers and fathers, abuse and satisfaction in delivery/abortion care, and the correlations between them and socioeconomic, obstetric, and child health factors. As a 2-component research, it consists of a prospective cohort study with all postpartum women interviewed in the 465 maternity hospitals included at the Birth in Brazil II baseline survey conducted from 2021 to 2023, and a cross-sectional study with the newborns' fathers/partners. Interviews will be conducted via telephone or self-completion link sent by WhatsApp with the mother at 2 and 4 months after delivery/abortion. Partners will be approached three months after birth (excluding abortions, stillbirths and newborn death) using the telephone number informed by the mother at the maternity ward. Postpartum women will be inquired about symptoms of depression, anxiety and post-traumatic stress disorder, abuse during maternity care and quality of the mother-newborn bond. Maternal and neonatal morbidity, use of postnatal services, and satisfaction with maternity care are also investigated. Fathers will be asked to report on symptoms of depression and anxiety, and the quality of the relationship with the partner and the newborn. The information collected in this research stage may help to plan and improve care aimed at the postpartum health of the mother-father-child triad.

A gravidez, o parto e o nascimento são momentos de grandes mudanças na vida das mães e dos pais. Este artigo tem como objetivo apresentar o protocolo da pesquisa para estimar a prevalência dos desfechos em saúde mental nas mães e pais no pós-parto, dos maus tratos e satisfação na atenção ao parto/abortamento, e as inter-relações entre eles e fatores socioeconômicos, obstétricos e da saúde da criança. A pesquisa tem dois componentes: estudo de coorte prospectiva com todas as puérperas entrevistadas nas 465 maternidades incluídas na linha de base da pesquisa Nascer no Brasil II realizada entre 2021 e 2023, e estudo seccional com os companheiros/pais dos bebês. As entrevistas são realizadas por ligação telefônica ou link de autopreenchimento enviado por WhatsApp com as puérperas aos 2 e 4 meses após o parto/aborto. Os companheiros são abordados três meses após o nascimento (excluídos os abortos, natimortos e neomortos), a partir do telefone informado pela puérpera na maternidade. As entrevistas abordam, entre as puérperas, sintomas de depressão, ansiedade e transtorno de estresse pós-traumático, maus-tratos na atenção na maternidade e qualidade do vínculo mãe-bebê. São investigados também a presença de morbidade materna e neonatal, utilização de serviços pós-natais, e satisfação com o atendimento na maternidade. Entre os pais, é abordada a ocorrência de sintomas de depressão e ansiedade, e a qualidade do relacionamento com a esposa/companheira e o bebê. As informações coletadas nessa etapa da pesquisa poderão subsidiar o planejamento e melhoria do cuidado voltado para a saúde da tríade mãe-pai-filho após o nascimento.

El embarazo, el parto y el nacimiento son momentos de grandes cambios en la vida de madres y padres. Este artículo tiene como objetivo presentar el protocolo de investigación para estimar la prevalencia de los resultados de la salud mental en madres y padres en el posparto, maltratos y la satisfacción durante la atención del parto/aborto, y las interrelaciones entre ellos y los factores socioeconómicos, obstétricos y de salud infantil. La investigación tiene dos componentes: un estudio de cohorte prospectivo con todas las puérperas entrevistadas en las 465 maternidades incluidas en la línea de base de la encuesta Nacer en Brasil II realizada entre 2021 y 2023, y un estudio seccional con las parejas/padres de los bebés. Las entrevistas se efectúan mediante llamada telefónica o enlace de autocumplimentación enviado vía WhatsApp a las puérperas a los 2 y 4 meses después del parto/aborto. El contacto con la pareja se hace a los tres meses del nacimiento (excluyendo abortos, mortinatos y muertes de recién nacidos), a través del teléfono facilitado por la puérpera en la sala de maternidad. Las entrevistas abordan, entre las puérperas, los síntomas de depresión, ansiedad y trastorno de estrés postraumático, maltrato durante la atención en la maternidad y la calidad del vínculo madre-bebé. También se investiga la presencia de morbilidad materna y neonatal, uso de servicios posnatales y satisfacción con la atención en la maternidad. Entre los padres, se aborda la ocurrencia de síntomas de depresión y ansiedad, y la calidad de la relación con la esposa/pareja y el bebé. La información recopilada en esta etapa de la investigación puede apoyar la planificación y mejora de la atención dirigida a la salud de la tríada madre-padre-hijo después del nacimiento.

Protocol of Birth in Brazil II: National Research on Abortion, Labor and Childbirth. / Protocolo do Nascer no Brasil II: Pesquisa Nacional sobre Aborto, Parto e Nascimento.

Brazil has made advances in obstetric care in public and private hospitals; however, weaknesses in this system still require attention. The Brazilian Ministry of Health, aware of this need, funded the second version of the Birth in Brazil survey. This study aimed to evaluate: prenatal, labor and birth, postpartum, and abortion care, comparing the results with those of Birth in Brazil I; and analyze the main determinants of perinatal morbidity and mortality; evaluate the care structure and processes of obstetrics and neonatology services in maternity hospitals; analyze the knowledge, practices, and attitudes of health professionals who provide birth and abortion care; and identify the main barriers and facilitators related to care of this nature in Brazil. With a national scope and a 2-stage probability sample: 1-hospitals and 2-women, stratified into 59 strata, 465 hospitals were selected with a total planned sample of around 24,255 women - 2,205 for abortion reasons and 22,050 for labor reasons. Data collection was conducted using six electronic instruments during hospital admission for labor or abortion, with two follow-up waves, at two and four months. In order to expand the number of cases of severe maternal morbidity, maternal and perinatal mortality, three case control studies were incorporated into Birth in Brazil II. The fieldwork began in November 2021 and is scheduled to end in 2023. It will allow a comparison between current labor and birth care results and those obtained in the first study and will evaluate the advances achieved in 10 years.

Com o passar do tempo, o Brasil vem apresentando avanços na assistência obstétrica em hospitais públicos e privados; no entanto, ainda existem pontos frágeis que necessitam de atenção. O Ministério da Saúde, ciente dessa necessidade, financiou a segunda versão da pesquisa Nascer no Brasil. Os objetivos gerais são: avaliar a assistência pré-natal, ao parto e nascimento, ao puerpério e ao aborto, comparando com os resultados do Nascer no Brasil I, e analisar os principais determinantes da morbimortalidade perinatal; avaliar a estrutura e processos assistenciais dos serviços de obstetrícia e neonatologia das maternidades; analisar os conhecimentos, atitudes e práticas de profissionais de saúde que prestam assistência ao parto e ao aborto; e identificar as principais barreiras e facilitadores para essa assistência no país. Com escopo nacional e amostra probabilística em dois estágios (1-hospitais e 2-mulheres), dividida em 59 estratos, foram selecionados 465 hospitais com total planejado de, aproximadamente, 24.255 mulheres, 2.205 por motivo de aborto e 22.050 por motivo de parto. A coleta de dados, realizada por meio de seis instrumentos eletrônicos, ocorre durante a internação hospitalar para o parto ou aborto, com duas ondas de seguimento, aos dois e quatro meses. Com o intuito de expandir o número de casos de morbidade materna grave, mortalidade materna e perinatal, três estudos caso controle foram incorporados ao Nascer no Brasil II. O trabalho de campo foi iniciado em novembro de 2021 com término previsto para 2023. Os resultados permitirão comparar a atenção atual ao parto e ao nascimento com a retratada no primeiro inquérito e, com isso, avaliar os avanços alcançados no decorrer desses 10 anos.

Aunque Brasil ha presentado avances en la atención obstétrica en hospitales públicos y privados, todavía hay puntos débiles que necesitan atención. El Ministerio de Salud, consciente de esta necesidad, financió la segunda versión de la encuesta Nacer en Brasil. Los objetivos generales son: evaluar la atención prenatal, el parto y el nacimiento, el puerperio y el aborto, comparando con los resultados del Nacer en Brasil I, y analizar los principales determinantes de la morbimortalidad perinatal; evaluar la estructura y los procesos de atención de los servicios de obstetricia y neonatología en las maternidades; analizar los conocimientos, prácticas y actitudes de los profesionales de la salud que brindan atención para el parto y el aborto; e identificar las principales barreras y facilitadores para esta atención en el país. Tiene un alcance nacional y muestra probabilística en dos etapas (1-hospitales y 2-mujeres), la cual se dividió en 59 estratos; y se seleccionaron 465 hospitales con un total planificado de aproximadamente 24.255 mujeres, de las cuales 2.205 tuvieron procedimientos por aborto y 22.050 por parto. Para la recolección de datos se aplicó seis instrumentos electrónicos, que se realizó durante la hospitalización por parto o aborto, con dos rondas de seguimiento, a los dos y cuatro meses. Con el fin de ampliar el número de casos de morbilidad materna grave, mortalidad materna y perinatal, se incorporaron tres estudios de casos y controles en Nacer en Brasil II. El trabajo de campo comenzó en noviembre de 2021 y finalizará en 2023. Los resultados nos permitirán evaluar la atención al parto y al nacimiento actual con lo que se retrató en la primera encuesta, de esta manera se podrá evaluar los avances alcanzados a lo largo de estos 10 años.

Bioprospecting of extremophilic perchlorate-reducing bacteria: report of promising Bacillus spp. isolated from sediments of the bay of Cartagena, Colombia.

Three extremophile bacterial strains (BBCOL-009, BBCOL-014 and BBCOL-015), capable of degrading high concentrations of perchlorate at a range of pH (6.5 to 10.0), were isolated from Colombian Caribbean Coast sediments. Morphological features included Gram negative strain bacilli with sizes averaged of 1.75 × 0.95, 2.32 × 0.65 and 3.08 × 0.70 µm, respectively. The reported strains tolerate a wide range of pH (6.5 to 10.0); concentrations of NaCl (3.5 to 7.5% w/v) and KClO4- (250 to 10000 mg/L), reduction of KClO4- from 10 to 25%. LB broth with NaCl (3.5-30% w/v) and KClO4- (250-10000 mg/L) were used in independent trials to evaluate susceptibility to salinity and perchlorate, respectively. Isolates increased their biomass at 7.5 % (w/v) NaCl with optimal development at 3.5 % NaCl. Subsequently, ClO4- reduction was assessed using LB medium with 3.5% NaCl and 10000 mg/L ClO4-. BBCOL-009, BBCOL-014 and BBCOL-015 achieved 10%, 17%, and 25% reduction of ClO4-, respectively. The 16 S rRNA gene sequence grouped them as Bacillus flexus T6186-2, Bacillus marisflavi TF-11 (T), and Bacillus vietnamensis 15 - 1 (T) respectively, with < 97.5% homology. In addition, antimicrobial resistance to ertapenem, vancomycine, amoxicillin clavulanate, penicillin, and erythromycin was present in all the isolates, indicating their high adaptability to stressful environments. The isolated strains from marine sediments in Cartagena Bay, Colombia are suitable candidates to reduce perchlorate contamination in different environments. Although the primary focus of the study of perchlorate-reducing and resistant bacteria is in the ecological and agricultural realms, from an astrobiological perspective, perchlorate-resistant bacteria serve as models for astrobiological investigations.

Dynamic microglia alterations associate with hippocampal network impairments: A turning point in amyloid pathology progression.

Alzheimer's disease is a progressive neurological disorder causing memory loss and cognitive decline. The underlying causes of cognitive deterioration and neurodegeneration remain unclear, leading to a lack of effective strategies to prevent dementia. Recent evidence highlights the role of neuroinflammation, particularly involving microglia, in Alzheimer's disease onset and progression. Characterizing the initial phase of Alzheimer's disease can lead to the discovery of new biomarkers and therapeutic targets, facilitating timely interventions for effective treatments. We used the AppNL-G-F knock-in mouse model, which resembles the amyloid pathology and neuroinflammatory characteristics of Alzheimer's disease, to investigate the transition from a pre-plaque to an early plaque stage with a combined functional and molecular approach. Our experiments show a progressive decrease in the power of cognition-relevant hippocampal gamma oscillations during the early stage of amyloid pathology, together with a modification of fast-spiking interneuron intrinsic properties and postsynaptic input. Consistently, transcriptomic analyses revealed that these effects are accompanied by changes in synaptic function-associated pathways. Concurrently, homeostasis- and inflammatory-related microglia signature genes were downregulated. Moreover, we found a decrease in Iba1-positive microglia in the hippocampus that correlates with plaque aggregation and neuronal dysfunction. Collectively, these findings support the hypothesis that microglia play a protective role during the early stages of amyloid pathology by preventing plaque aggregation, supporting neuronal homeostasis, and overall preserving the oscillatory network's functionality. These results suggest that the early alteration of microglia dynamics could be a pivotal event in the progression of Alzheimer's disease, potentially triggering plaque deposition, impairment of fast-spiking interneurons, and the breakdown of the oscillatory circuitry in the hippocampus.

Migration process of Venezuelan women to Brazil: living conditions and use of health services in Manaus and Boa Vista, 2018-2021.

BACKGROUND: The last decade saw the emergence of a new significant migration corridor due to the mass migration of Venezuelans to neighboring countries in South America. Since 2018, Brazil became the third host country of Venezuelan displaced populations. Little is known about how migratory processes affect needs, access to social programs, and public health services of migrant women. The goal of this study is to shed light on the socio-economic profile, living conditions, and use of health services of Venezuelan migrant women in two main reception cities in Brazil. METHODS: A survey was conducted using respondent-driven sampling (RDS) in the cities of Boa Vista (Roraima), and Manaus (Amazonas). The study included 2012 Venezuelan migrant women aged between 15 and 49 years old who migrated from Venezuela to Brazil between 2018 and 2021. Relative prevalence was calculated, and the χ2 test was used to analyse the homogeneity of proportions. All analyses considered the complex sampling. RESULTS: The main reasons for migrating relate to difficulties obtaining food (54%) and accessing health services (37.8%) in their country of origin. They were young and mixed race (65.7%) and had high school education (69.9%). In Manaus, 3.7% of the interviewees declared that they had no family income in the last month, while in Boa Vista, it was higher (66.2%) (p-value < 0.001). Almost one-third of them sought health care in the last 15 days, and 95% of them received care. The residents of Boa Vista arrived more recently and family income and access to paid work improved with time of residence in Brazil. CONCLUSIONS: Given the increasing flow of Venezuelan migrants crossing to Brazil, a reception system was established for the provision of food, shelter, access to health services, and income transfer programs to migrants. This was the case despite high unemployment and poverty levels and income inequality, particularly in the city of Boa Vista. However, the majority had legal migrant status and had access to the public and universal healthcare system in Brazil (SUS). The use of the SUS was similar in both cities, acting as a buffer for the differences in opportunities offered.

Impaired astrocytic synaptic function by peripheral cholesterol metabolite 27-hydroxycholesterol.

Astrocytes represent the most abundant cell type in the brain, where they play critical roles in synaptic transmission, cognition, and behavior. Recent discoveries show astrocytes are involved in synaptic dysfunction during Alzheimer's disease (AD). AD patients have imbalanced cholesterol metabolism, demonstrated by high levels of side-chain oxidized cholesterol known as 27-hydroxycholesterol (27-OH). Evidence from our laboratory has shown that elevated 27-OH can abolish synaptic connectivity during neuromaturation, but its effect on astrocyte function is currently unclear. Our results suggest that elevated 27-OH decreases the astrocyte function in vivo in Cyp27Tg, a mouse model of brain oxysterol imbalance. Here, we report a downregulation of glutamate transporters in the hippocampus of CYP27Tg mice together with increased GFAP. GLT-1 downregulation was also observed when WT mice were fed with high-cholesterol diets. To study the relationship between astrocytes and neurons, we have developed a 3D co-culture system that allows all the cell types from mice embryos to differentiate in vitro. We report that our 3D co-cultures reproduce the effects of 27-OH observed in 2D neurons and in vivo. Moreover, we found novel degenerative effects in astrocytes that do not appear in 2D cultures, together with the downregulation of glutamate transporters GLT-1 and GLAST. We propose that this transporter dysregulation leads to neuronal hyperexcitability and synaptic dysfunction based on the effects of 27-OH on astrocytes. Taken together, these results report a new mechanism linking oxysterol imbalance in the brain and synaptic dysfunction through effects on astrocyte function.

[Factors associated with breastfeeding at birth in maternity hospitals linked to the Rede Cegonha, Brazil, 2016-2017]. / Fatores associados ao aleitamento materno ao nascer em maternidades vinculadas à Rede Cegonha, Brasil, 2016-2017.

Breastfeeding (BF) is a human right, and it must start from birth. The adequacy of Rede Cegonha (RC) strategies can contribute to the promotion of BF. The objective was to identify factors associated with BF in the first and 24 hours of live births at full-term maternity hospitals linked to CR. Cross-sectional study with data from the second evaluation cycle 2016-2017 of the RC that covered all of Brazil. Odds ratios were obtained through binary logistic regression according to a hierarchical model, with 95% confidence intervals and p-value < 0.01. The prevalence of BF in the first hour was 31% and in the 24 hours 96.6%. The chances of BF in the first hour increased: presence of a companion during hospitalization, skin-to-skin contact, vaginal delivery, delivery assistance by a nurse and accreditation of the unit in the Baby-Friendly Hospital Initiative. Similar results at 24 hours, and association with maternal age below 20 years. BF in the first hour was less satisfactory than in the 24 hours, probably due to the high prevalence of cesarean sections, a factor associated with a lower chance of early BF. Continuous training of professionals about BF and the presence of an obstetric nurse during childbirth are recommended to expand BF in the first hour.

O aleitamento materno (AM) é um direito humano e deve ser iniciado desde o nascimento. A adequação das estratégias da Rede Cegonha (RC) pode contribuir na promoção do AM. O objetivo foi identificar os fatores associados ao AM na primeira e nas 24 horas de nascidos vivos a termo em maternidades vinculadas à RC. Estudo transversal com dados do segundo ciclo avaliativo 2016-2017 da RC, que abrangeu todo o Brasil. Foram obtidas razões de chance por meio de regressão logística binária segundo modelo hierarquizado, com intervalos de confiança a 95% e p-valor < 0,01. A prevalência de AM na primeira hora foi de 31%, e nas 24 horas, de 96,6%. Aumentaram as chances de AM na primeira hora: presença de acompanhante na internação, contato pele a pele, parto vaginal, assistência ao parto por enfermeira e acreditação da unidade na Iniciativa Hospital Amigo da Criança. Resultados semelhantes nas 24 horas, e associação com idade materna inferior a 20 anos. O AM na primeira hora foi menos satisfatório do que nas 24h, provavelmente pela elevada prevalência de cesariana, fator associado à menor chance de AM precoce. A capacitação dos profissionais sobre AM de forma contínua e a presença de enfermeiro obstetra no parto são recomendadas para ampliar o AM na primeira hora.

An implementation analysis of a quality improvement project to reduce cesarean section in Brazilian private hospitals.

BACKGROUND: Brazil has one of the highest prevalence of cesarean sections in the world. The private health system is responsible for carrying out most of these surgical procedures. A quality improvement project called Adequate Childbirth Project ("Projeto Parto Adequado"- PPA) was developed to identify models of care for labor and childbirth, which place value on vaginal birth and reduce the frequency of cesarean sections without a clinical indication. This research aims to evaluate the implementation of PPA in private hospitals in Brazil. METHOD: Evaluative hospital-based survey, carried out in 2017, in 12 private hospitals, including 4,322 women. We used a Bayesian network strategy to develop a theoretical model for implementation analysis. We estimated and compared the degree of implementation of two major driving components of PPA-"Participation of women" and "Reorganization of care" - among the 12 hospitals and according to type of hospital (belonging to a health insurance company or not). To assess whether the degree of implementation was correlated with the rate of vaginal birth data we used the Bayesian Network and compared the difference between the group "Exposed to the PPA model of care" and the group "Standard of care model". RESULTS: PPA had a low degree of implementation in both components "Reorganization of Care" (0.17 - 0.32) and "Participation of Women" (0.21 - 0.34). The combined implementation score was 0.39-0.64 and was higher in hospitals that belonged to a health insurance company. The vaginal birth rate was higher in hospitals with a higher degree of implementation of PPA. CONCLUSION: The degree of implementation of PPA was low, which reflects the difficulties in changing childbirth care practices. Nevertheless, PPA increased vaginal birth rates in private hospitals with higher implementation scores. PPA is an ongoing quality improvement project and these results demonstrate the need for changes in the involvement of women and the care offered by the provider.

Women's preference for a vaginal birth in Brazilian private hospitals: effects of a quality improvement project.

BACKGROUND: In 2015, a quality improvement project called "Adequate Childbirth Project" (PPA) was implemented in Brazilian private hospitals in order to reduce cesarean sections without clinical indication. The PPA is structured in four components, one of which is directed at women and families. The objective of this study is to evaluate the effects of PPA on women's preference for vaginal birth (VB) at the end of pregnancy. METHODS: Evaluative research conducted in 12 private hospitals participating in the PPA. Interviews were carried out in the immediate postpartum period and medical record data were collected at hospital discharge. The implementation of PPA activities and women's preference for type of birth at the beginning and end of pregnancy were compared in women assisted in the PPA model of care and in the standard of care model, using a chi-square statistical test. To estimate the effect of PPA on women's preference for VB at the end of pregnancy, multiple logistic regression was performed with selection of variables using a causal diagram. RESULTS: Four thousand seven hundred ninety-eight women were interviewed. The implementation of the planned activities of PPA was less than 50%, but were significantly more frequent among women assisted in the PPA model of care. Women in this group also showed a greater preference for VB at the beginning and end of pregnancy. The PPA showed an association with greater preference for VB at the end of pregnancy in primiparous (OR 2.54 95% CI 1.99-3.24) and multiparous women (OR 1.44 95% CI 0.97-2.12), although in multiparous this association was not significant. The main factor associated with the preference for VB at the end of pregnancy was the preference for this type of birth at the beginning of pregnancy, both in primiparous (OR 18.67 95% CI 14.22-24.50) and in multiparous women (OR 53.11 95% CI 37.31-75.60). CONCLUSIONS: The PPA had a positive effect on women's preference for VB at the end of pregnancy. It is plausible that more intense effects are observed with the expansion of the implementation of the planned activities. Special attention should be given to information on the benefits of VB in early pregnancy.

Cesarean rates have been increasing worldwide and constitute the most frequent type of childbirth in Brazil since 2009. In 2015, a quality improvement project was implemented in Brazilian private hospitals, with the objective of reducing medically unnecessary cesarean sections and increasing the number of vaginal births. This project, called "Adequate Childbirth Project" (PPA), has four components, one of which is directed at women and families, aiming to increase their participation in decision-making processes related to childbirth. In this study, we assessed whether this program contributed to increased preference for vaginal birth at the end of pregnancy. In previous studies in Brazil, we saw that women who maintained preference for vaginal birth throughout pregnancy were those who had the lowest proportion of cesarean sections. We found that the PPA increased preference for vaginal birth by almost three times in primiparous women. Among women with previous births, this increase was smaller. In this group of women, having a previous cesarean section was an important factor for not wanting a vaginal birth, and this is a very common condition in Brazil. For all women, having preference for vaginal birth at the beginning of pregnancy was the main factor in wanting this type of birth at the end of pregnancy. The results demonstrate the importance of educational activities that disseminate information about the benefits of vaginal birth, increasing the preference of women for this type of childbirth, in addition to supporting them throughout pregnancy, so that they feel empowered in their choice.

Costs-effectiveness and cost components of pharmaceutical and non-pharmaceutical interventions affecting antibiotic resistance outcomes in hospital patients: a systematic literature review.

INTRODUCTION: Limited information on costs and the cost-effectiveness of hospital interventions to reduce antibiotic resistance (ABR) hinder efficient resource allocation. METHODS: We conducted a systematic literature review for studies evaluating the costs and cost-effectiveness of pharmaceutical and non-pharmaceutical interventions aimed at reducing, monitoring and controlling ABR in patients. Articles published until 12 December 2023 were explored using EconLit, EMBASE and PubMed. We focused on critical or high-priority bacteria, as defined by the WHO, and intervention costs and incremental cost-effectiveness ratio (ICER). Following Preferred Reporting Items for Systematic review and Meta-Analysis guidelines, we extracted unit costs, ICERs and essential study information including country, intervention, bacteria-drug combination, discount rates, type of model and outcomes. Costs were reported in 2022 US dollars ($), adopting the healthcare system perspective. Country willingness-to-pay (WTP) thresholds from Woods et al 2016 guided cost-effectiveness assessments. We assessed the studies reporting checklist using Drummond's method. RESULTS: Among 20 958 articles, 59 (32 pharmaceutical and 27 non-pharmaceutical interventions) met the inclusion criteria. Non-pharmaceutical interventions, such as hygiene measures, had unit costs as low as $1 per patient, contrasting with generally higher pharmaceutical intervention costs. Several studies found that linezolid-based treatments for methicillin-resistant Staphylococcus aureus were cost-effective compared with vancomycin (ICER up to $21 488 per treatment success, all 16 studies' ICERs

CYP46A1-mediated cholesterol turnover induces sex-specific changes in cognition and counteracts memory loss in ovariectomized mice.

The brain-specific enzyme CYP46A1 controls cholesterol turnover by converting cholesterol into 24S-hydroxycholesterol (24OH). Dysregulation of brain cholesterol turnover and reduced CYP46A1 levels are observed in Alzheimer's disease (AD). In this study, we report that CYP46A1 overexpression in aged female mice leads to enhanced estrogen signaling in the hippocampus and improved cognitive functions. In contrast, age-matched CYP46A1 overexpressing males show anxiety-like behavior, worsened memory, and elevated levels of 5α-dihydrotestosterone in the hippocampus. We report that, in neurons, 24OH contributes to these divergent effects by activating sex hormone signaling, including estrogen receptors. CYP46A1 overexpression in female mice protects from memory impairments induced by ovariectomy while having no effects in gonadectomized males. Last, we measured cerebrospinal fluid levels of 24OH in a clinical cohort of patients with AD and found that 24OH negatively correlates with neurodegeneration markers only in women. We suggest that CYP46A1 activation is a valuable pharmacological target for enhancing estrogen signaling in women at risk of developing neurodegenerative diseases.

Individualised, perioperative open-lung ventilation strategy during one-lung ventilation (iPROVE-OLV): a multicentre, randomised, controlled clinical trial.

BACKGROUND: It is uncertain whether individualisation of the perioperative open-lung approach (OLA) to ventilation reduces postoperative pulmonary complications in patients undergoing lung resection. We compared a perioperative individualised OLA (iOLA) ventilation strategy with standard lung-protective ventilation in patients undergoing thoracic surgery with one-lung ventilation. METHODS: This multicentre, randomised controlled trial enrolled patients scheduled for open or video-assisted thoracic surgery using one-lung ventilation in 25 participating hospitals in Spain, Italy, Turkey, Egypt, and Ecuador. Eligible adult patients (age ≥18 years) were randomly assigned to receive iOLA or standard lung-protective ventilation. Eligible patients (stratified by centre) were randomly assigned online by local principal investigators, with an allocation ratio of 1:1. Treatment with iOLA included an alveolar recruitment manoeuvre to 40 cm H2O of end-inspiratory pressure followed by individualised positive end-expiratory pressure (PEEP) titrated to best respiratory system compliance, and individualised postoperative respiratory support with high-flow oxygen therapy. Participants allocated to standard lung-protective ventilation received combined intraoperative 4 cm H2O of PEEP and postoperative conventional oxygen therapy. The primary outcome was a composite of severe postoperative pulmonary complications within the first 7 postoperative days, including atelectasis requiring bronchoscopy, severe respiratory failure, contralateral pneumothorax, early extubation failure (rescue with continuous positive airway pressure, non-invasive ventilation, invasive mechanical ventilation, or reintubation), acute respiratory distress syndrome, pulmonary infection, bronchopleural fistula, and pleural empyema. Due to trial setting, data obtained in the operating and postoperative rooms for routine monitoring were not blinded. At 24 h, data were acquired by an investigator blinded to group allocation. All analyses were performed on an intention-to-treat basis. This trial is registered with ClinicalTrials.gov, NCT03182062, and is complete. FINDINGS: Between Sept 11, 2018, and June 14, 2022, we enrolled 1380 patients, of whom 1308 eligible patients (670 [434 male, 233 female, and three with missing data] assigned to iOLA and 638 [395 male, 237 female, and six with missing data] to standard lung-protective ventilation) were included in the final analysis. The proportion of patients with the composite outcome of severe postoperative pulmonary complications within the first 7 postoperative days was lower in the iOLA group compared with the standard lung-protective ventilation group (40 [6%] vs 97 [15%], relative risk 0·39 [95% CI 0·28 to 0·56]), with an absolute risk difference of -9·23 (95% CI -12·55 to -5·92). Recruitment manoeuvre-related adverse events were reported in five patients. INTERPRETATION: Among patients subjected to lung resection under one-lung ventilation, iOLA was associated with a reduced risk of severe postoperative pulmonary complications when compared with conventional lung-protective ventilation. FUNDING: Instituto de Salud Carlos III and the European Regional Development Funds.

A Higher Skeletal Muscle Mass and Lower Adiposity Phenotype Is Associated with Better Cardiometabolic Control in Adults with Hip and Knee Osteoarthritis: Results from the Chilean National Health Survey 2016-2017.

OBJECTIVE: This study aimed to (1) characterize cardiometabolic factors in self-reported hip and knee osteoarthritis (OAD) across four body composition phenotypes defined by muscle mass and adiposity, and (2) associate risk factors with diabetes and hypertension (HTN). METHODS: A cross-sectional analysis of the Chilean National Health Survey 2016-17 (n = 4996) stratified participants into four groups: low skeletal muscle mass/high waist circumference (Low-SMM/High-WC), low SMM/low WC (Low-SMM/Low-WC), high SMM/high WC (High-SMM/High-WC), and high SMM/low WC (reference group). Each group was further divided into subgroups with or without diagnosed hip or knee OAD. The main outcomes were fasting plasma glucose, systolic (SBP)/diastolic (DBP) blood pressure (continuous outcomes), and other secondary factors such as cardiovascular risk (CVR). RESULTS: In the hip OAD subgroup, the Low-SMM/High-WC groups had significantly higher SBP versus the reference value (145 vs. 127 mmHg, p < 0.0001, diff +18 mmHg). In the knee OAD subgroup, the Low-SMM/High-WC groups had significantly higher SBP versus the reference value (141 vs. 134 mmHg, p < 0.0001, diff +7 mmHg). The SBP showed a significant interaction between the group and OAD diagnosis (p = 0.007 hip OAD; p < 0.0001 knee OAD). CONCLUSIONS: Hip and knee OAD associates with elevated SBP/DBP in older adults. OAD groups showed an OR above 2 for diabetes, 2.7 for HTN, 4.5 for metabolic syndrome, and over 2 for moderate-to-high cardiovascular risk. OAD interacts substantially with cardiometabolic factors, especially in low muscle mass/high adiposity phenotypes. Lifestyle optimization of physical activity and nutrition to preserve muscle mass and mitigate adiposity is essential for cardiometabolic health promotion in OAD patients.

Does the duration of ambulatory consultations affect the quality of healthcare? A systematic review.

BACKGROUND: The objective is to examine and synthesise the best available experimental evidence about the effect of ambulatory consultation duration on quality of healthcare. METHODS: We included experimental studies manipulating the length of outpatient clinical encounters between adult patients and clinicians (ie, therapists, pharmacists, nurses, physicians) to determine their effect on quality of care (ie, effectiveness, efficiency, timeliness, safety, equity, patient-centredness and patient satisfaction). INFORMATION SOURCES: Using controlled vocabulary and keywords, without restriction by language or year of publication, we searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials and Database of Systematic Reviews and Scopus from inception until 15 May 2023. RISK OF BIAS: Cochrane Risk of Bias instrument. DATA SYNTHESIS: Narrative synthesis. RESULTS: 11 publications of 10 studies explored the relationship between encounter duration and quality. Most took place in the UK's general practice over two decades ago. Study findings based on very sparse and outdated evidence-which suggested that longer consultations improved indicators of patient-centred care, education about prevention and clinical referrals; and that consultation duration was inconsistently related to patient satisfaction and clinical outcomes-warrant low confidence due to limited protections against bias and indirect applicability to current practice. CONCLUSION: Experimental evidence for a minimal or optimal duration of an outpatient consultation is sparse and outdated. To develop evidence-based policies and practices about encounter length, randomised trials of different consultation lengths-in person and virtually, and with electronic health records-are needed. TRIAL REGISTRATION NUMBER: OSF Registration DOI:10.17605/OSF.IO/EUDK8.

Microglia-secreted TNF-α affects differentiation efficiency and viability of pluripotent stem cell-derived human dopaminergic precursors.

Disease is a neurodegenerative disorder characterised by the progressive loss of dopaminergic cells of the substantia nigra pars compacta. Even though successful transplantation of dopamine-producing cells into the striatum exhibits favourable effects in animal models and clinical trials; transplanted cell survival is low. Since every transplant elicits an inflammatory response which can affect cell survival and differentiation, we aimed to study in vivo and in vitro the impact of the pro-inflammatory environment on human dopaminergic precursors. We first observed that transplanted human dopaminergic precursors into the striatum of immunosuppressed rats elicited an early and sustained activation of astroglial and microglial cells after 15 days' post-transplant. This long-lasting response was associated with Tumour necrosis factor alpha expression in microglial cells. In vitro, conditioned media from activated BV2 microglial cells increased cell death, decreased Tyrosine hydroxylase-positive cells and induced morphological alterations on human neural stem cells-derived dopaminergic precursors at two differentiation stages: 19 days and 28 days. Those effects were ameliorated by inhibition of Tumour necrosis factor alpha, a cytokine which was previously detected in vivo and in conditioned media from activated BV-2 cells. Our results suggest that a pro-inflammatory environment is sustained after transplantation under immunosuppression, providing a window of opportunity to modify this response to increase transplant survival and differentiation. In addition, our data show that the microglia-derived pro-inflammatory microenvironment has a negative impact on survival and differentiation of dopaminergic precursors. Finally, Tumour necrosis factor alpha plays a key role in these effects, suggesting that this cytokine could be an interesting target to increase the efficacy of human dopaminergic precursors transplantation in Parkinson's Disease.