Avdoralimab (Anti-C5aR1 mAb) Versus Placebo in Patients With Severe COVID-19: Results From a Randomized Controlled Trial (FOR COVID Elimination [FORCE]).

OBJECTIVES: Severe COVID-19 is associated with exaggerated complement activation. We assessed the efficacy and safety of avdoralimab (an anti-C5aR1 mAb) in severe COVID-19. DESIGN: FOR COVID Elimination (FORCE) was a double-blind, placebo-controlled study. SETTING: Twelve clinical sites in France (ICU and general hospitals). PATIENTS: Patients receiving greater than or equal to 5 L oxygen/min to maintain Sp o2 greater than 93% (World Health Organization scale ≥ 5). Patients received conventional oxygen therapy or high-flow oxygen (HFO)/noninvasive ventilation (NIV) in cohort 1; HFO, NIV, or invasive mechanical ventilation (IMV) in cohort 2; and IMV in cohort 3. INTERVENTIONS: Patients were randomly assigned, in a 1:1 ratio, to receive avdoralimab or placebo. The primary outcome was clinical status on the World Health Organization ordinal scale at days 14 and 28 for cohorts 1 and 3, and the number of ventilator-free days at day 28 (VFD28) for cohort 2. MEASUREMENTS AND MAIN RESULTS: We randomized 207 patients: 99 in cohort 1, 49 in cohort 2, and 59 in cohort 3. During hospitalization, 95% of patients received glucocorticoids. Avdoralimab did not improve World Health Organization clinical scale score on days 14 and 28 (between-group difference on day 28 of -0.26 (95% CI, -1.2 to 0.7; p = 0.7) in cohort 1 and -0.28 (95% CI, -1.8 to 1.2; p = 0.6) in cohort 3). Avdoralimab did not improve VFD28 in cohort 2 (between-group difference of -6.3 (95% CI, -13.2 to 0.7; p = 0.96) or secondary outcomes in any cohort. No subgroup of interest was identified. CONCLUSIONS: In this randomized trial in hospitalized patients with severe COVID-19 pneumonia, avdoralimab did not significantly improve clinical status at days 14 and 28 (funded by Innate Pharma, ClinicalTrials.gov number, NCT04371367).

Antitumor immunity induced by antibody-based natural killer cell engager therapeutics armed with not-alpha IL-2 variant.

Harnessing innate immunity is emerging as a promising therapeutic approach in cancer. We report here the design of tetraspecific molecules engaging natural killer (NK) cell-activating receptors NKp46 and CD16a, the ß-chain of the interleukin-2 receptor (IL-2R), and a tumor-associated antigen (TAA). In vitro, these tetraspecific antibody-based natural killer cell engager therapeutics (ANKETs) induce a preferential activation and proliferation of NK cells, and the binding to the targeted TAA triggers NK cell cytotoxicity and cytokine and chemokine production. In vivo, tetraspecific ANKETs induce NK cell proliferation and their accumulation at the tumor bed, as well as the control of local and disseminated tumors. Treatment of non-human primates with CD20-directed tetraspecific ANKET leads to CD20+ circulating B cell depletion, with minimal systemic cytokine release and no sign of toxicity. Tetraspecific ANKETs, thus, constitute a technological platform for harnessing NK cells as next-generation cancer immunotherapies.

Single-cell transcriptomic landscape reveals tumor specific innate lymphoid cells associated with colorectal cancer progression.

Innate lymphoid cells (ILCs) are tissue-resident lymphocytes differing from conventional T lymphocytes in having no antigen-specific receptors. ILCs include natural killer (NK) cells, helper-like ILC1s, ILC2s, and ILC3s, and lymphoid tissue-inducer (LTi) cells. Tumor ILCs are frequently found in various cancers, but their roles in cancer immunity and immunotherapy remain largely unclear. We report here the single-cell characterization of blood and gut helper-like ILC subsets in healthy conditions and in colorectal cancer (CRC). The healthy gut contains ILC1s, ILC3s, and ILC3/NKs, but no ILC2s. Additional tumor-specific ILC1-like and ILC2 subsets were identified in CRC patients. Signaling lymphocytic activation molecule family member 1 (SLAMF1) was found to be selectively expressed on tumor-specific ILCs, and higher levels of SLAMF1+ ILCs were observed in the blood of CRC patients. The SLAMF1-high group of CRC patients had a significantly higher survival rate than the SLAMF1-low group, suggesting that SLAMF1 is an anti-tumor biomarker in CRC.

Diálogos da enfermagem durante a pandemia: reflexões, desafios e perspectivas para a integração ensino-serviço / Nursing dialogues during the pandemic: reflections, challenges and perspectives for teaching-service integration / Diálogos de enfermería durante la pandemia: reflexiones, desafíos y perspectivas para la integración enseñanza-servcio

Objetivo: abordar, de forma crítica e reflexiva, desafios e perspectivas da prática profissional da enfermagem, da formação e da integração ensino-serviço no cenário da pandemia da Covid-19. Método: as atividades práticas de uma disciplina, que aborda a gestão do Sistema Único de Saúde, foram suspensas durante a pandemia. Diante desse fato, constituiu-se um grupo para discutir a prática profissional, assegurando a integração ensino-serviço. A partir dos diálogos e dos textos produzidos elaborou-se essa reflexão, tendo como referencial teórico a Análise Institucional. Resultados: alguns analisadores revelaram desafios como a influência e o difícil acesso às tecnologias digitais no ensino e no processo de trabalho, além do medo e da insegurança vivenciados pelas autoras. O grupo analisou suas implicações, compartilhando sentimentos e angústias, sem perder de vista as mudanças necessárias nos processos de trabalho. Conclusão e implicações para a prática: a Análise Institucional contribuiu para realizar este estudo "à quente", nesse contexto de pandemia, trazendo à tona questionamentos e contradições vivenciadas nos serviços de saúde e na universidade, fortalecendo a integração ensino-serviço. Mas, mediante o recorte de tempo, práticas e cenários este estudo traz limitações quanto aos impactos para o ensino e para a assistência prestada, possibilitando a realização de outras pesquisas

Objective: critically and reflexively address challenges and perspectives of professional nursing practice, training, and teachingservice integration in the context of the Covid-19 pandemic. Method: the practical activities of a discipline that addresses the management of the Unified Health System were suspended during the pandemic. In view of this fact, a group was formed to discuss the professional practice, ensuring the teaching-service integration. From the dialogues and texts produced, this reflection was elaborated, using Institutional Analysis as a theoretical framework. Results: some analyzers revealed challenges such as the influence and difficult access to digital technologies in teaching and in the work process, as well as the fear and insecurity experienced by the authors. The group analyzed their implications, sharing feelings and anguish, without losing sight of the necessary changes in the work processes. Conclusion and implications for the practice: the Institutional Analysis contributed to carry out this study "in the heat of the moment", in this pandemic context, bringing to light questions and contradictions experienced in health services and in the university, strengthening the teaching-service integration. But, due to the cut-off of time, practices and scenarios, this study has limitations regarding the impacts on teaching and the care provided, making it possible to carry out other research

Objetivo: abordar de manera crítica y reflexiva, los desafíos y perspectivas de la práctica profesional de enfermería, de la formación y la integración enseñanza-servicio en el escenario de la pandemia Covid-19. Método: las actividades prácticas de una disciplina, que aborda la gestión del Sistema Único de Salud, fueron suspendidas durante la pandemia. Ante este hecho, se formó un grupo para discutir la práctica profesional, asegurando la integración entre enseñanza y servicio. A partir de los diálogos y textos producidos, se elaboró esta reflexión, teniendo como marco teórico el Análisis Institucional. Resultados: algunos analizadores revelaron desafíos como la influencia y el difícil acceso a las tecnologías digitales en la enseñanza y en el proceso de trabajo, además del miedo y la inseguridad vivenciados por las autoras. El grupo analizó sus implicaciones, compartiendo sentimientos y ansiedades, sin perder de vista los cambios necesarios en los procesos de trabajo. Conclusión e implicaciones para la práctica: El Análisis Institucional contribuyó a realizar este estudio "en caliente", en este contexto de pandemia, planteando interrogantes y contradicciones vividas en los servicios de salud y en la universidad, fortaleciendo la integración enseñanza -servicio. Pero, a través del recorte de tiempo, prácticas y escenarios, este estudio trae limitaciones en cuanto a los impactos para la enseñanza y la asistencia brindada, permitiendo la realización de otras investigaciones

Association of COVID-19 inflammation with activation of the C5a-C5aR1 axis.

Coronavirus disease 2019 (COVID-19) is a disease caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has resulted in a pandemic1. The C5a complement factor and its receptor C5aR1 (also known as CD88) have a key role in the initiation and maintenance of several inflammatory responses by recruiting and activating neutrophils and monocytes1. Here we provide a longitudinal analysis of immune responses, including phenotypic analyses of immune cells and assessments of the soluble factors that are present in the blood and bronchoalveolar lavage fluid of patients at various stages of COVID-19 severity, including those who were paucisymptomatic or had pneumonia or acute respiratory distress syndrome. The levels of soluble C5a were increased in proportion to the severity of COVID-19 and high expression levels of C5aR1 receptors were found in blood and pulmonary myeloid cells, which supports a role for the C5a-C5aR1 axis in the pathophysiology of acute respiratory distress syndrome. Anti-C5aR1 therapeutic monoclonal antibodies prevented the C5a-mediated recruitment and activation of human myeloid cells, and inhibited acute lung injury in human C5aR1 knock-in mice. These results suggest that blockade of the C5a-C5aR1 axis could be used to limit the infiltration of myeloid cells in damaged organs and prevent the excessive lung inflammation and endothelialitis that are associated with acute respiratory distress syndrome in patients with COVID-19.

Analytical validation of the Immunoscore and its associated prognostic value in patients with colon cancer.

BACKGROUND: New and fully validated tests need to be brought into clinical practice to improve the estimation of recurrence risk in patients with colon cancer. The aim of this study was to assess the analytical performances of the Immunoscore (IS) and show its contribution to prognosis prediction. METHODS: Immunohistochemical staining of CD3+ and CD8+ T cells on adjacent sections of colon cancer tissues were quantified in the core of the tumor and its invasive margin with dedicated IS modules integrated into digital pathology software. Staining intensity across samples collected between 1989 and 2016 (n=595) was measured. The accuracy of the IS workflow was established by comparing optical and automatic counts. Analytical precision of the IS was evaluated within individual tumor block on distant sections and between eligible blocks. The IS interlaboratory reproducibility (n=100) and overall assay precision were assessed (n=3). Contribution of the IS to prediction of recurrence based on clinical and molecular parameters was determined (n=538). RESULTS: Optical and automatic counts for CD3+ or CD8+ were strongly correlated (r=0.94, p<0.001 and r=0.92, p<0.001, respectively). CD3 and CD8 staining intensities were not altered by the age of the tumor block over a period of 30 years. Neither the position of tested tissue sections within a tumor block nor the selection of the tissue blocks affected the IS. Reproducibility of the IS was not affected by multiple variables (eg, antibody lots, DAB revelation kits, immunohistochemistry automates and operators). Interassay repeatability of the IS was 100% and interlaboratory reproducibility between two testing centers was 93%. Finally, in a case series of patients with stage II-III colon cancer, the relative proportion of variance for time to recurrence was greatest for the IS (53% of prognostic variability) in a model that included IS, T-stage, microsatellite instability status and total number of lymph nodes. CONCLUSION: IS is a robust and validated clinical assay leveraging immune scoring to predict recurrence risk of patient with localized colon cancer. The strong and independent prognostic value of IS should pave the way for it use in clinical practice.

Os principais fatores causadores de Estresse em profissionais de enfermagem que atuam em Unidade de Terapia Intensiva / The main factors causing Stress in nursing professionals who work in the Intensive Care Unit / Los principales factores que causan estrés en los profesionales de enfermería que trabajan en la Unidad de Cuidados Intensivos

Objetivo: identificar os principais fatores causadores de Estresse nos profissionais de enfermagem que atuam em Unidade de Terapia Intensiva. Método: Trata-se de um artigo de revisão integrativa realizado através da análise de 6 artigos científicos extraídos da biblioteca virtual de saúde. Resultados: foram identificados os principais fatores causadores do estresse nesses profissionais, como: baixa remuneração, múltiplos vínculos, incluindo as tarefas domésticas como jornada de trabalho, tempo de atuação, cansaço físico, privação do sono e rotinas da UTI (contato constante com sofrimento, morte, ruídos dos equipamentos entre outro). Conclusão: as próprias funções da profissão e as responsabilidades designadas a esses profissionais requer esforço e dedicação, pois causam diversas alterações físicas, emocionais e psicológicas, que impactam na saúde, e consequentemente, na segurança e qualidade da assistência prestada aos pacientes.

Objective: to identify the main factors that cause stress in nursing professionals working in the Intensive Care Unit. Method: This is an integrative review article carried out through the analysis of 6 scientific articles extracted from the virtual health library. Results: the main factors causing stress in these professionals were identified, such as: low remuneration, multiple bonds, including domestic chores such as working hours, working hours, physical tiredness, sleep deprivation and ICU routines (constant contact with suffering, death, equipment noise, among others). Conclusion: the profession's own functions and the responsibilities assigned to these professionals require effort and dedication, as they cause various physical, emotional and psychological changes, which impact on health, and consequently, on the safety and quality of care provided to patients.

Objetivo: identificar los principales factores que causan estrés en los profesionales de enfermería que trabajan en la Unidad de Cuidados Intensivos. Método: Este es un artículo de revisión integrador realizado a través del análisis de 6 artículos científicos extraídos de la biblioteca virtual de salud. Resultados: se identificaron los principales factores que causan estrés en estos profesionales, tales como: baja remuneración, múltiples vínculos, incluidos los quehaceres domésticos, como las horas de trabajo, las horas de trabajo, el cansancio físico, la privación del sueño y las rutinas de la UCI (contacto constante con el sufrimiento, muerte, ruido de equipo, entre otros). Conclusión: las funciones propias de la profesión y las responsabilidades asignadas a estos profesionales requieren esfuerzo y dedicación, ya que causan varios cambios físicos, emocionales y psicológicos, que afectan la salud y, en consecuencia, la seguridad y la calidad de la atención brindada a los pacientes.

Elaboração de roteiro de sistematização da assistência de enfermagem na atenção à gestante: proposta de utilização da CIPESC / Development of the Nursing Care Systematization guide in care for pregnant women: proposal to use CIPESC®

A sistematização da assistência de enfermagem tornou-se um instrumento valioso no trabalho do enfermeiro, por nortear as consultas, produzir registro de suas práticas por meio de processo organizado com linguagem padronizada, pensamento crítico e habilidades lógicas. Na Atenção Básica, para o enfermeiro realizar a SAE, necessita de classificação voltada não apenas para o modelo fisiopatológico, mas que contemple o ser humano de forma integral, respeitando os princípios do SUS de universalidade, equidade, integralidade, resolutividade e de qualidade. A Classificação Internacional de Práticas de Enfermagem em Saúde Coletiva, CIPESC®, atende a essas características, constituindo a opção de classificação para esta elaboração. Assim, o presente estudo teve como objetivo reformular e validar roteiro para primeira consulta de enfermagem à gestante de baixo risco utilizando a CIPESC®. A pesquisa buscou consistência teórica no histórico das classificações das práticas de enfermagem para contribuir no aprimoramento do conhecimento, assim como, na consulta de enfermagem e da saúde da mulher para entendermos a evolução do atendimento à gestante, grupo populacional escolhido como foco do roteiro. Trata-se de Estudo Metodológico realizado em duas fases. A primeira constituiu-se no desenvolvimento de revisão integrativa, analisando as produções científicas sobre Cuidados de Enfermagem, Enfermagem em Saúde Pública, Atenção Primária à Saúde, Saúde da Mulher, Classificação Internacional de Atenção Primária, Gestante e Pré-Natal para fundamentar a reconstrução do roteiro em uso em uma unidade básica de saúde. Foram utilizadas três bases de dados: Lilacs, Pubmed e Cinahl. Obteve-se nove publicações que possibilitaram extrair evidências das informações para aprimorar o roteiro. O resultado da Revisão Integrativa acrescido de analise de documentos oficiais do Ministério da Saúde sobre o tema forneceram os elementos para a formulação do roteiro, que também foi apreciado pelo grupo de trabalho sobre a SAE, constituído de enfermeiras da rede de Atenção Básica, gerando a versão para a próxima fase. Na segunda fase, foi realizada validação por oito experts que, após duas apreciações com incorporação das observações e sugestões, obteve-se como produto final, o roteiro de SAE para primeira consulta da gestante na Atenção Básica. Conclui-se que o roteiro validado oferece subsídios para direcionar os enfermeiros a documentarem a consulta de enfermagem, permitindo além da adequação das exigências do Conselho de Enfermagem espaço para novos estudos relacionados à sua aplicabilidade. O roteiro reformulado e validado, de sistematização de assistência de enfermagem da primeira consulta à gestante na Atenção Básica visa, como finalidade, à sua aplicação prática, para tanto, será apresentado à Secretária Municipal de Saúde do município de Ribeirão Preto para ser incorporado aos protocolos municipais, propondo-se a substituição da Versão inicial atualmente em uso

The Nursing Care Systematization (NCS) has become a valuable tool in the nurses' work for guiding the consultations and producing a record of their practices through an organized process with standardized language, critical thinking and logical skills. In Primary Care, to perform the NCS, nurses need of the classification not only for the pathophysiological model, but also to contemplate the human being integrally, respecting the SUS principles of universality, equity, integrality, problem solving and quality. The International Classification of the Nursing Practices in Collective Health - CIPESC® meets these characteristics, constituting the option of classification for this development. Thus, this study aimed to reformulate and validate a guide for the first nursing consultation of the low-risk pregnant women using the CIPESC®. The research sought theoretical consistency in the history of the classification of nursing practices to contribute to the improvement of knowledge as well as of the nursing consultation and women's health to understand the evolution of care to pregnant women, a population group chosen as the focus of the guide. This is a Methodological Study carried out in two phases. The first was the development of an integrative review, analyzing the scientific productions on Nursing Care, Public Health Nursing, Primary Health Care, Women's Health, International Classification of Primary Care, Pregnant Women and Prenatal Care to support the reconstruction of the guide which was being used in a basic health unit. Three databases were used: Lilacs, Pubmed and Cinahl. There were 9 articles that made it possible to extract evidence of the information to improve the guide. The result of the Integrative Review and the analysis of official Ministry of Health documents on the theme provided the elements for the development of the guide, which was also appreciated by the work group on NCS composed by nurses from the Primary Care network, generating the version for the next phase. In the second phase, the validation was performed by 8 experts, and after two evaluations with incorporation of the observations and suggestions, it was obtained as final product, the NCS guide for the first consultation of the pregnant women in Primary Care. It was concluded that the validated guide offers subsidies to help nurses to document the nursing consultation, allowing the adequacy of the requirements of the Nursing Board and the opportunity for further studies related to its applicability. The revised and validated guide of the systematization of first nursing consultation of the pregnant woman in Primary Care aimed at its practical application. For this purpose, it will be presented to the Municipal Health Secretary of the city of Ribeirão Preto to be incorporated into the municipal protocols with the proposal to replace the initial version, which is currently in use

Elaboração de roteiro de sistematização da assistência de enfermagem na atenção à gestante: proposta de utilização da CIPESC / Development of the Nursing Care Systematization guide in care for pregnant women: proposal to use CIPESC®

A sistematização da assistência de enfermagem tornou-se um instrumento valioso no trabalho do enfermeiro, por nortear as consultas, produzir registro de suas práticas por meio de processo organizado com linguagem padronizada, pensamento crítico e habilidades lógicas. Na Atenção Básica, para o enfermeiro realizar a SAE, necessita de classificação voltada não apenas para o modelo fisiopatológico, mas que contemple o ser humano de forma integral, respeitando os princípios do SUS de universalidade, equidade, integralidade, resolutividade e de qualidade. A Classificação Internacional de Práticas de Enfermagem em Saúde Coletiva, CIPESC®, atende a essas características, constituindo a opção de classificação para esta elaboração. Assim, o presente estudo teve como objetivo reformular e validar roteiro para primeira consulta de enfermagem à gestante de baixo risco utilizando a CIPESC®. A pesquisa buscou consistência teórica no histórico das classificações das práticas de enfermagem para contribuir no aprimoramento do conhecimento, assim como, na consulta de enfermagem e da saúde da mulher para entendermos a evolução do atendimento à gestante, grupo populacional escolhido como foco do roteiro. Trata-se de Estudo Metodológico realizado em duas fases. A primeira constituiu-se no desenvolvimento de revisão integrativa, analisando as produções científicas sobre Cuidados de Enfermagem, Enfermagem em Saúde Pública, Atenção Primária à Saúde, Saúde da Mulher, Classificação Internacional de Atenção Primária, Gestante e Pré-Natal para fundamentar a reconstrução do roteiro em uso em uma unidade básica de saúde. Foram utilizadas três bases de dados: Lilacs, Pubmed e Cinahl. Obteve-se nove publicações que possibilitaram extrair evidências das informações para aprimorar o roteiro. O resultado da Revisão Integrativa acrescido de analise de documentos oficiais do Ministério da Saúde sobre o tema forneceram os elementos para a formulação do roteiro, que também foi apreciado pelo grupo de trabalho sobre a SAE, constituído de enfermeiras da rede de Atenção Básica, gerando a versão para a próxima fase. Na segunda fase, foi realizada validação por oito experts que, após duas apreciações com incorporação das observações e sugestões, obteve-se como produto final, o roteiro de SAE para primeira consulta da gestante na Atenção Básica. Conclui-se que o roteiro validado oferece subsídios para direcionar os enfermeiros a documentarem a consulta de enfermagem, permitindo além da adequação das exigências do Conselho de Enfermagem espaço para novos estudos relacionados à sua aplicabilidade. O roteiro reformulado e validado, de sistematização de assistência de enfermagem da primeira consulta à gestante na Atenção Básica visa, como finalidade, à sua aplicação prática, para tanto, será apresentado à Secretária Municipal de Saúde do município de Ribeirão Preto para ser incorporado aos protocolos municipais, propondo-se a substituição da Versão inicial atualmente em uso

The Nursing Care Systematization (NCS) has become a valuable tool in the nurses' work for guiding the consultations and producing a record of their practices through an organized process with standardized language, critical thinking and logical skills. In Primary Care, to perform the NCS, nurses need of the classification not only for the pathophysiological model, but also to contemplate the human being integrally, respecting the SUS principles of universality, equity, integrality, problem solving and quality. The International Classification of the Nursing Practices in Collective Health - CIPESC® meets these characteristics, constituting the option of classification for this development. Thus, this study aimed to reformulate and validate a guide for the first nursing consultation of the low-risk pregnant women using the CIPESC®. The research sought theoretical consistency in the history of the classification of nursing practices to contribute to the improvement of knowledge as well as of the nursing consultation and women's health to understand the evolution of care to pregnant women, a population group chosen as the focus of the guide. This is a Methodological Study carried out in two phases. The first was the development of an integrative review, analyzing the scientific productions on Nursing Care, Public Health Nursing, Primary Health Care, Women's Health, International Classification of Primary Care, Pregnant Women and Prenatal Care to support the reconstruction of the guide which was being used in a basic health unit. Three databases were used: Lilacs, Pubmed and Cinahl. There were 9 articles that made it possible to extract evidence of the information to improve the guide. The result of the Integrative Review and the analysis of official Ministry of Health documents on the theme provided the elements for the development of the guide, which was also appreciated by the work group on NCS composed by nurses from the Primary Care network, generating the version for the next phase. In the second phase, the validation was performed by 8 experts, and after two evaluations with incorporation of the observations and suggestions, it was obtained as final product, the NCS guide for the first consultation of the pregnant women in Primary Care. It was concluded that the validated guide offers subsidies to help nurses to document the nursing consultation, allowing the adequacy of the requirements of the Nursing Board and the opportunity for further studies related to its applicability. The revised and validated guide of the systematization of first nursing consultation of the pregnant woman in Primary Care aimed at its practical application. For this purpose, it will be presented to the Municipal Health Secretary of the city of Ribeirão Preto to be incorporated into the municipal protocols with the proposal to replace the initial version, which is currently in use

Regulation of miR-200c/141 expression by intergenic DNA-looping and transcriptional read-through.

The miR-200 family members have been implicated in stress responses and ovarian tumorigenesis. Here, we find that miR-200c/141 transcription is intimately linked to the transcription of the proximal upstream gene PTPN6 (SHP1) in all physiological conditions tested. PTPN6 and miR-200c/141 are transcriptionally co-regulated by two complementary mechanisms. First, a bypass of the regular PTPN6 polyadenylation signal allows the transcription of the downstream miR-200c/141. Second, the promoters of the PTPN6 and miR-200c/141 transcription units physically interact through a 3-dimensional DNA loop and exhibit similar epigenetic regulation. Our findings highlight that transcription of intergenic miRNAs is a novel outcome of transcriptional read-through and reveal a yet unexplored type of DNA loop associating two closely located promoters. These mechanisms have significant relevance in ovarian cancers and stress response, pathophysiological conditions in which miR-200c/141 exert key functions.

Desenvolvimento bucal e aleitamento materno em crianças com fissura labiopalatal / Oral development and breastfeeding in children with cleft lip and palate

OBJETIVO:Aspectos funcionais do estado de saúde bucal de crianças portadoras de fissuras de lábio e/ou palato interferem na capacidade natural de serem adequadamente alimentadas, como também em seu crescimento e desenvolvimento. Essa revisão visou verificar a influência do aleitamento materno sobre o desenvolvimento buco-maxilo-facial em crianças com fissuras labiais. FONTES DE DADOS: Revisão das bases de dados Medline e SciELO entre 2000 e 2010, utilizando os termos: "fenda labial", "fissura palatina", "aleitamento materno", "alimentação artificial" e "higiene bucal". As informações foram agrupadas, de modo a estabelecer a relação entre a amamentação natural e artificial no desenvolvimento bucofacial e estado de saúde bucal. SÍNTESE DOS DADOS: A pesquisa inicial selecionou um total de 27.046 artigos, dos quais 26.793 abordaram o aleitamento materno e a alimentação artificial, 119 relacionavam a influência do aleitamento materno sobre o desenvolvimento bucofacial, enquanto 134 analisaram a relação entre a amamentação e o estado de saúde bucal. Foram selecionados para a análise 34 artigos, sendo 20 com crianças portadoras de fendas labiais e/ou fissuras palatinas. CONCLUSÕES: O aleitamento natural em crianças portadoras de fissuras de lábio e/ou palato é fator decisivo para a correta maturação e crescimento craniofacial em nível ósseo, muscular e funcional e na prevenção de problemas bucais. Além disso, essas crianças apresentam maior prevalência de cárie dental, problemas relacionados à doença periodontal, podendo ainda apresentar problemas de má oclusão.

OBJECTIVE:Functional aspects of oral health of children with cleft lip and/or palate interfere in their possibility of being naturally fed, as well as in their growth and development. This review aimed to verify the influence of breastfeeding on orofacial development of children with cleft lip and/or palate. DATA SOURCES: Data were obtained by literature search (2000-2010) of Medline and SciELO databases, using as key-words "cleft lip", "cleft palate", "breast feeding", "complementary feeding" and "oral hygiene". Information was grouped in order to establish the relationship between natural breastfeeding and complementary feeding with orofacial development and oral health status. DATA SYNTHESIS: Initial search retrieved 27,046 articles and in 26,793 of them, the subject was breastfeeding and complementary feeding. Among those, there were 119 about the influence of breastfeeding on orofacial development and 134 about the relationship between breastfeeding and oral health status; 34 articles were selected and in 20 children with cleft lip and/or palate were enrolled. CONCLUSIONS: Breastfeeding in children with cleft lip and/or palate is a decisive factor not only for correct craniofacial maturation and growth at bone, muscular and functional levels, but also for the prevention of oral problems. These children present higher prevalence of dental caries, periodontal diseases, as well as occlusion related problems.

miR-141 and miR-200a act on ovarian tumorigenesis by controlling oxidative stress response.

Although there is evidence that redox regulation has an essential role in malignancies, its impact on tumor prognosis remains unclear. Here we show crosstalk between oxidative stress and the miR-200 family of microRNAs that affects tumorigenesis and chemosensitivity. miR-141 and miR-200a target p38α and modulate the oxidative stress response. Enhanced expression of these microRNAs mimics p38α deficiency and increases tumor growth in mouse models, but it also improves the response to chemotherapeutic agents. High-grade human ovarian adenocarcinomas that accumulate miR-200a have low concentrations of p38α and an associated oxidative stress signature. The miR200a-dependent stress signature correlates with improved survival of patients in response to treatment. Therefore, the role of miR-200a in stress could be a predictive marker for clinical outcome in ovarian cancer. In addition, although oxidative stress promotes tumor growth, it also sensitizes tumors to treatment, which could account for the limited success of antioxidants in clinical trials.

População indígena: uma reflexão sobre a influência da civilização urbana no estado nutricional e na saúde bucal / Indigenous peoples: reflection about the influence of urban civilization on nutritional status and oral health

Embora ainda existam sociedades indígenas que mantêm um modo tradicional de viver, nas quais uma alimentação adequada em quantidade e qualidade provém da caça e da prática de agricultura, a maioria dos índios vem sofrendo um processo de aculturação oriundo do contato com a civilização urbana, pois eles não mais dispõem de terra suficiente que garanta a subsistência. Desse modo, acabam tornando-se dependentes do comércio local e consumindo alimentos industrializados que podem ser prejudiciais à saúde bucal e ao estado nutricional. A presente comunicação tem como objetivo identificar a influência da transição alimentar, devido ao contato com a civilização urbana, no estado nutricional e na condição bucal da população indígena brasileira. Os dados relacionados nessa investigação foram obtidos na base de dados do SciELO e do MedLine, PubMed, pesquisando-se os termos de indexação: "índios sul-americanos", "comportamento alimentar", "estado nutricional", "saúde bucal". Estudos revelaram a prevalência de desnutrição infantil, sobrepeso e obesidade em adultos, índice de cárie elevado e doença periodontal nas comunidades indígenas que vêm passando por mudanças de hábitos culturais. Conclui-se que a transição alimentar pode levar a desordens nutricionais e ao desenvolvimento de doenças bucais, sugerindo a necessidade de uma intervenção e/ou monitoramento por meio de programas dirigidos à assistência à saúde, ao saneamento básico, ao acesso à terra e à educação.

Although there are still some indigenous societies that have maintained their traditional way of life, where food consumption in terms of amount and quality is based on hunting and agriculture, most indigenous peoples have been undergoing an acculturation process secondary to the contact with urban civilizations, since they no longer have enough land to guarantee their subsistence. Thus, they become dependent on local trade and consume processed foods that may be harmful to their oral health and nutritional status. The objective of this communication is to identify the influence of the dietary transition due to contact with urban civilization on the nutritional status and oral condition of native Brazilian populations. The data included in this investigation were obtained from the SciELO and MedLine, PubMed databases using the keywords: "South American natives", "dietary behavior", "nutritional status", "oral health". Studies have revealed a prevalence of childhood malnutrition, adult overweight and obesity, high caries rates and periodontal disease in the native Brazilian communities that have been experiencing changes in their cultural habits. In conclusion, dietary transition can lead to nutritional disorders and the development of oral diseases, suggesting the need for health care and basic sanitation programs and access to land and education, in order to intervene in or monitor these occurrences.

Oral health and nutritional status of semi-institutionalized persons with mental retardation in Brazil.

Association between oral health status and nutritional status was investigated in 200 semi-institutionalized persons with mental retardation aged 5-53 years, 45.5% female, in the cities of Florianópolis and São José, province of Santa Catarina, Brazil. In this cross-sectional study, clinical-odontological examination revealed a high percentage of individuals (68%) with heavily compromised dentition. The index of decayed, missing and filled deciduous and permanent teeth, which increased from 2.85+/-2.87 in children to 20.5+/-6.86 units in adults, was used to classify the individuals' oral health status. Anthropometric evaluation revealed the prevalence of suboptimal nutritional status in 52% of children and adolescents [22% underweight, 30% at risk of overweight or overweight], and in 60% of adults [7% underweight, 53% overweight or obese]. Significant association was found between unsatisfactory oral health status and overweight in children (chi(2)=4.627; p=0.031). Findings evidenced the existence of a relationship between oral health status and nutritional status in persons with mental retardation.

Planos de assistência à saúde: interfaces entre o público e o privado no setor odontológico / Health care plans: interfaces between the public and private system in the dental sector

O presente trabalho vislumbra um breve histórico dos planos de saúde no Brasil, examinando as interfaces entre o público e o privado. Realiza, ainda, uma análise da evolução e regulamentação da saúde suplementar, definindo as modalidades assistenciais de saúde, bem como enuncia as principais diferenças entre os planos e assistência médico-hospitalar e odontológico. Demonstra, em dados atuais, a cobertura exercida pelos planos de saúde suplementar e sua relação com a assistência pública de saúde. Por outro lado, enfoca a assistência, planos de saúde e o mercado de trabalho da odontologia, correlacionando, também com dados atuais, os desafios e as novas oportunidades do mercado de saúde suplementar, enfocado principalmente no setor odontológico. Ainda que o setor odontológico esteja em um momento extraordinário dentro do sistema privado de atenção à saúde, e que dados da ANS apontem para um crescimento desse setor de 210 por cento nos últimos sete anos, a cobertura de serviços do setor suplementar de saúde está aquém das reais demandas, não contemplando, portanto, a assistência integral à saúde.

The present work presents a brief history of health plans in Brazil examining the interface between the public and the private sector. The evolution and regulation of the supplementary care system is analyzed, the different care modalities are defined and the main differences between health plans and dental care insurance are pointed out. The coverage provided by the supplementary care system and its relationship with the public health system is shown on the basis of current data. On the other hand, the study focuses on the care services, health plans and the labor market in the sector correlating, also on the basis of current data, the challenges and new opportunities of the supplementary care market, mainly in the dental sector. Although the dental sector is living an extraordinary moment within the private health care system and given that ANS data are pointing to a growth of this sector of 210 percent over last the 7 years, the service coverage of the supplementary care sector mainly directed to medical and inpatient care does not meet the real demand for integrated health care.

[Health care plans: interfaces between the public and private system in the dental sector]. / Planos de assistência à saúde: interfaces entre o público e o privado no setor odontológico.

The present work presents a brief history of health plans in Brazil examining the interface between the public and the private sector. The evolution and regulation of the supplementary care system is analyzed, the different care modalities are defined and the main differences between health plans and dental care insurance are pointed out. The coverage provided by the supplementary care system and its relationship with the public health system is shown on the basis of current data. On the other hand, the study focuses on the care services, health plans and the labor market in the sector correlating, also on the basis of current data, the challenges and new opportunities of the supplementary care market, mainly in the dental sector. Although the dental sector is living an extraordinary moment within the private health care system and given that ANS data are pointing to a growth of this sector of 210% over last the 7 years, the service coverage of the supplementary care sector mainly directed to medical and inpatient care does not meet the real demand for integrated health care.

Alimentação, estado nutricional e condição bucal da criança / Food, nutritional status and oral condition of the child

A relação entre alimentação, estado nutricional e a condição bucal ainda não está bem esclarecida, apresentando, muitas vezes, versões controversas e conhecimento limitado. Existe certa concordância de que a alimentação e, conseqüentemente, o estado nutricional, possam exercer certa influência sobre a condição bucal imediata e futura da criança. O objetivo desta comunicação é apresentar possíveis relações entre alimentação, estado nutricional e a condição bucal da criança. O estado nutricional pode afetar os dentes durante o seu período de formação e após a erupção na cavidade bucal. Os efeitos sistêmicos provenientes da nutrição podem alterar o desenvolvimento dos dentes, a quantidade e a qualidade da saliva, assim como os efeitos externos também podem determinar uma maior prevalência de cárie dentária, uma vez que tanto a quantidade de sacarose ingerida, quanto a freqüência de ingestão são importantes fatores envolvidos em sua etiologia. As reflexões deste trabalho sugerem a necessidade de ações interdisciplinares para obtenção de resultados na prevenção e no tratamento das doenças bucais.

The relationship among food, nutritional status and oral condition is not yet well established, many times presenting controversial versions and limited knowledge. There seems to be an agreement that eating, and consequently, the nutritional status, may have a certain amount of influence over present and future oral conditions of the child. The objective of this communication is to discuss possible relations among food, nutritional status and oral condition in the child. Nutritional status may affect the teeth during their formation period and after eruption in the oral cavity. Systemic effects of nutrition may alter the development of teeth, quantity and quality of saliva, and the external effect may also determine a bigger prevalence of dental cavities, since both the quantity and the frequency of saccharose ingestion are important factors involved in their etiology. The reflections contained in this paper suggest that interdisciplinary actions are necessary in order to obtain results in the prevention and treatment of oral diseases.