Lei do acompanhante na mídia: a pandemia e suas implicações nos direitos do parto / Companion Law in the media: the pandemic and its impacts on birth rights

Resumo Gestantes têm direito a acompanhante de sua escolha durante o período de internação, pré-parto, parto e pós-parto, em todo o território nacional garantido pela Lei 11.108/2005. Contudo, com a pandemia da covid-19, protocolos de saúde restringiram esses direitos sob o argumento de cuidados contra o vírus. Buscou-se compreender abordagens, atores envolvidos e argumentações sobre o descumprimento da lei de acompanhante durante a pandemia de covid-19 por meio de análise de matérias do portal G1 publicadas de março de 2020 a abril de 2022, utilizando o recurso de mapas. Os dados evidenciaram que o descumprimento da Lei do Acompanhante se concentrou no primeiro semestre de 2020 e as principais justificativas foram questões de biossegurança, falta de orçamento para compras de equipamentos de proteção individual e o momento atípico. Em vários locais foram necessárias intervenções jurídicas para cumprimento da lei, tornando-se pauta jornalística, e o caso mais emblemático foi o do Tocantins, cuja proibição perdurou até abril de 2022. Houve uma discrepância em relação à garantia do direito em diversos municípios e estados, apesar do Ministério da Saúde e diversos órgãos jurídicos terem emitido pareceres e protocolos recomendando a presença de acompanhante.

Abstract Pregnant women have the right to a companion of their choice during hospitalization, pre-delivery, delivery and postpartum, a right assured nationwide by Law no. 11,108, implemented in 2005. However, health protocols have restricted these rights on the grounds of mitigating the COVID-19 pandemic. Hence, this study sought to understand the approaches, actors involved, and arguments presented about noncompliance with the Companion Law during the COVID-19 pandemic by analyzing G1 Portal news articles published from March 2020 to April 2022, using the map feature. Results show that failure to comply with the aforementioned law occurred most often in the first half of 2020, justified by biosafety issues, lack of budget for purchasing personal protective equipment, and the atypical moment. In several places legal intervention was necessary for compliance, becoming a journalistic agenda, with the most emblematic case happening in Tocantins, where the veto lasted until April 2022. Analysis showed a discrepancy regarding law compliance in several municipalities and states, despite the Ministry of Health and several legal bodies having issued opinions and protocols recommending the presence of a companion.

The production of health news by the press: the context of the coverage of the 2007/2008 yellow fever epidemic. / A produção de notícias de saúde pela imprensa: o contexto da cobertura da epizootia da febre amarela 2007/2008.

The COVID-19 pandemic scenario raises the amplification of the debate around the production and circulation of information about epidemics. In this sense, the objective of this article is to discuss how social contexts shape the news, taking as an example the case of the news coverage that transformed an epizootic of yellow fever, in the summer of 2007/2008, into an epidemic of urban yellow fever. This is a qualitative research with journalists who worked in two large circulation newspapers and actively participated in the coverage of the event. The interviews were recorded, transcribed and submitted to discourse analysis, which allowed the identification of three factors that influenced the production of a media epidemic of yellow fever: the working conditions and the modus operandi of the newsrooms; the political-ideological dimension of the newspapers; and the difficulties of translation of technical-scientific information. A critical understanding of the production process of the journalistic text can contribute to the construction of communication strategies that minimize the circulation of misinformation on public health in traditional media (newspapers, magazines, radio, TV and news portals).

O cenário da pandemia de COVID-19 suscita a ampliação do debate em torno da produção e circulação de informações sobre epidemias. Nesse sentido, o objetivo deste artigo é discutir como os contextos sociais configuram as notícias, tomando como exemplo o caso da cobertura jornalística que transformou uma epizootia de febre amarela, no verão 2007/2008, em uma epidemia de febre amarela urbana. Trata-se de uma pesquisa qualitativa com jornalistas que trabalhavam em dois jornais de grande circulação e participaram ativamente da cobertura do evento. As entrevistas foram gravadas, transcritas e submetidas à análise de discurso, o que permitiu identificar três fatores que influenciaram a produção de uma epidemia midiática de febre amarela: as condições de trabalho e o modus operandi das redações; a dimensão político-ideológica dos jornais; e as dificuldades de tradução das informações técnico-científicas. A compreensão crítica do processo de produção do texto jornalístico pode contribuir para a construção de estratégias comunicacionais que minimizem a circulação de desinformação em saúde pública nas mídias tradicionais (jornais, revistas, rádio, tevê e portais de notícias).

A produção de notícias de saúde pela imprensa: o contexto da cobertura da epizootia da febre amarela 2007/2008 / The production of health news by the press: the context of the coverage of the 2007/2008 yellow fever epidemic

Resumo O cenário da pandemia de COVID-19 suscita a ampliação do debate em torno da produção e circulação de informações sobre epidemias. Nesse sentido, o objetivo deste artigo é discutir como os contextos sociais configuram as notícias, tomando como exemplo o caso da cobertura jornalística que transformou uma epizootia de febre amarela, no verão 2007/2008, em uma epidemia de febre amarela urbana. Trata-se de uma pesquisa qualitativa com jornalistas que trabalhavam em dois jornais de grande circulação e participaram ativamente da cobertura do evento. As entrevistas foram gravadas, transcritas e submetidas à análise de discurso, o que permitiu identificar três fatores que influenciaram a produção de uma epidemia midiática de febre amarela: as condições de trabalho e o modus operandi das redações; a dimensão político-ideológica dos jornais; e as dificuldades de tradução das informações técnico-científicas. A compreensão crítica do processo de produção do texto jornalístico pode contribuir para a construção de estratégias comunicacionais que minimizem a circulação de desinformação em saúde pública nas mídias tradicionais (jornais, revistas, rádio, tevê e portais de notícias).

Abstract The COVID-19 pandemic scenario raises the amplification of the debate around the production and circulation of information about epidemics. In this sense, the objective of this article is to discuss how social contexts shape the news, taking as an example the case of the news coverage that transformed an epizootic of yellow fever, in the summer of 2007/2008, into an epidemic of urban yellow fever. This is a qualitative research with journalists who worked in two large circulation newspapers and actively participated in the coverage of the event. The interviews were recorded, transcribed and submitted to discourse analysis, which allowed the identification of three factors that influenced the production of a media epidemic of yellow fever: the working conditions and the modus operandi of the newsrooms; the political-ideological dimension of the newspapers; and the difficulties of translation of technical-scientific information. A critical understanding of the production process of the journalistic text can contribute to the construction of communication strategies that minimize the circulation of misinformation on public health in traditional media (newspapers, magazines, radio, TV and news portals).

Most-cited public health articles of scientific journals from Brazil.

OBJECTIVE: To describe the most-cited articles in public health scientific journals edited in Brazil. METHODS: Articles published between 2008 and 2010 by public health journals edited in Brazil and indexed in the Scopus database were included, and citations received up to five years after publication were ranked. We studied a total of 105 articles, as the last seven articles shared the same number of citations and so were given the same rank. RESULTS: The most-cited articles received a median of 28 citations, and the distribution ranged from 22 to 95 citations. These articles describe advances in the areas of Epidemiology (74%), Health Policies, Planning and Administration (19%), and Social and Human Sciences in Health (7%). Only half mentioned that they have received funding. About 75% of the articles were written by three or more authors and 90%, by authors affiliated to public institutions such as universities and government organizations. Fifteen individuals were responsible for authoring or coauthoring three or more of the 105 articles studied. The journals Cadernos de Saúde Pública, Revista de Saúde Pública, and Ciência & Saúde Coletiva have published the vast majority of the most-cited articles in the area (94%). CONCLUSIONS: In Brazil, the most-cited articles in public health mainly report Epidemiology research, are written by groups of authors and by researchers affiliated to public institutions and are published in journals with a greater impact. Periodical analyses of these data can show potential changes in the characteristics of articles that most attract public health scientists.

Most-cited public health articles of scientific journals from Brazil

ABSTRACT OBJECTIVE To describe the most-cited articles in public health scientific journals edited in Brazil. METHODS Articles published between 2008 and 2010 by public health journals edited in Brazil and indexed in the Scopus database were included, and citations received up to five years after publication were ranked. We studied a total of 105 articles, as the last seven articles shared the same number of citations and so were given the same rank. RESULTS The most-cited articles received a median of 28 citations, and the distribution ranged from 22 to 95 citations. These articles describe advances in the areas of Epidemiology (74%), Health Policies, Planning and Administration (19%), and Social and Human Sciences in Health (7%). Only half mentioned that they have received funding. About 75% of the articles were written by three or more authors and 90%, by authors affiliated to public institutions such as universities and government organizations. Fifteen individuals were responsible for authoring or coauthoring three or more of the 105 articles studied. The journals Cadernos de Saúde Pública, Revista de Saúde Pública, and Ciência & Saúde Coletiva have published the vast majority of the most-cited articles in the area (94%). CONCLUSIONS In Brazil, the most-cited articles in public health mainly report Epidemiology research, are written by groups of authors and by researchers affiliated to public institutions and are published in journals with a greater impact. Periodical analyses of these data can show potential changes in the characteristics of articles that most attract public health scientists.

Uncited articles in Brazilian public health journals.

Here, we describe the percentage of non-citation in Brazilian public health journals, a field that, until now, had not been investigated nationally or internationally. We analyzed articles, published between 2008 and 2012, of eight public health journals indexed in the scopus database. The percentage of non-citation differs between journals (from 5.7% to 58.1%). We identified four statistically distinct groups: História, Ciência, Saúde - Manguinhos (58% uncited articles); Physis: Revista de Saúde Coletiva, Interface, and Saúde e Sociedade (32% to 37%); Ciência & Saúde Coletiva and Revista Brasileira de Epidemiologia (16% to 17%); and Cadernos de Saúde Pública and Revista de Saúde Pública (6%). The non-citation in the first three years post-publication also varies according to journal. Four journals have shown a clear decline of non-citation: Cadernos de Saúde Pública, Ciência & Saúde Coletiva, Revista Brasileira de Epidemiologia, and Physis. Another three (Revista de Saúde Pública, Saúde e Sociedade, and Interface) presented an oscillation in non-citation, but the rates of 2008 and 2012 are similar, with different magnitudes. In turn, the journal História, Ciência, Saúde - Manguinhos maintains high rates of non-citation. Multidisciplinary journals attract more citation, but a comprehensive citation model still needs to be formulated and tested.

Desenvolvimento da habilidade na escrita e a produção científica: cursos são necessários? / Writing skills development and scientific production: are needed courses? / El desarrollo de la habilidad en la escritura y la producción científica: son necesarios cursos?

Este artigo é resultado de um estudo que tem como objetivo identificar se o aprimoramento do conhecimento sobre a produção de artigos científicos, reforçado por cursos de escrita científica, vem facilitando ao pesquisador (autor) a publicação de seus artigos. Entendemos que a relevância do estudo se deve ao reconhecimento da importância de investimentos no aprimoramento do pesquisador para a divulgação científica. Foi identificada a produção bibliográfica de egressos de cursos de aprimoramento da habilidade na escrita científica e comparada com o percurso de publicações desse egresso, antes e depois do curso. Foram utilizadas duas fontes de informação de acesso público para identificar a produção bibliográfica, científica e técnica, do pesquisador: currículo na Plataforma Lattes do CNPq; e fontes de dados bibliográficos: Lilacs e PubMed. Observou-se que o número de artigos publicados foi maior após a participação em um dos cursos e que, embora outros fatores influenciem na produção, iniciativas dessa natureza estimulam a divulgação científica.(AU)

This paper is product of a study to identify if the improvement in knowledge about writing scientific papers reinforced by writing courses had facilitated the publication by researcher (author) of his articles. We understand the relevance of the study is due to the recognition of the importance of investments intraining courses for researchers to improve the scientific dissemination of their papers. We identified the bibliographic production of the participants in courses on scientific writing, and then we compared it withthe number of publications by then prior to and after the course. We searched two public information sources to identify the scientific and technical bibliographic production by researcher: curriculum in the Plataforma Lattes do CNPq (Brazil) and bibliographic databases: Lilacs (Bireme/OPS) and PubMed. We observed that the number of papers published increased after the participation in one of these courses. Although other factors may influence the production, such initiatives stimulate scientific communication.

Este artículo es resultado de estudio que tiene el objetivo de identificar si la mejora en el conocimiento sobre como escribir artículos científicos, reforzada por los cursos de escritura científica, ha facilitado para el investigador (autor) la publicación de sus artículos. Entendemos que la relevancia del estudio se debe al reconocimiento de la importancia de inversiones en cursos de capacitación para investigadores que permitan ampliar la divulgación científica. Identificamos la producción bibliográfica de participantes de cursos de redacción científica y comparamos el número de publicaciones del participante antes y despuésdel curso. Se han utilizado dos fuentes de información a la disposición del público para identificar la producción bibliográfica, científica y técnica, del investigador: la Plataforma Lattes do CNPq (Brasil); y basede datos bibliográficos: Lilacs (Bireme/OPAS) y PubMed. Se observó que el número de artículos publicados fue mayor después de la participación en el curso. Aunque otros factores puedan influir en la producción, tales iniciativas estimulan la divulgación científica.

Uncited articles in Brazilian public health journals / Artigos não citados nas revistas brasileiras em saúde pública

ABSTRACT Here, we describe the percentage of non-citation in Brazilian public health journals, a field that, until now, had not been investigated nationally or internationally. We analyzed articles, published between 2008 and 2012, of eight public health journals indexed in the scopus database. The percentage of non-citation differs between journals (from 5.7% to 58.1%). We identified four statistically distinct groups: História, Ciência, Saúde - Manguinhos (58% uncited articles); Physis: Revista de Saúde Coletiva, Interface, and Saúde e Sociedade (32% to 37%); Ciência & Saúde Coletiva and Revista Brasileira de Epidemiologia (16% to 17%); and Cadernos de Saúde Pública and Revista de Saúde Pública (6%). The non-citation in the first three years post-publication also varies according to journal. Four journals have shown a clear decline of non-citation: Cadernos de Saúde Pública, Ciência & Saúde Coletiva, Revista Brasileira de Epidemiologia, and Physis. Another three (Revista de Saúde Pública, Saúde e Sociedade, and Interface) presented an oscillation in non-citation, but the rates of 2008 and 2012 are similar, with different magnitudes. In turn, the journal História, Ciência, Saúde - Manguinhos maintains high rates of non-citation. Multidisciplinary journals attract more citation, but a comprehensive citation model still needs to be formulated and tested.

RESUMO Aqui, descrevemos o percentual de não citação em revistas brasileiras de saúde pública, campo até agora não investigado nacional ou internacionalmente. Analisamos artigos, publicados entre 2008 e 2012, de oito revistas de saúde pública indexadas na base Scopus. O percentual de não citação difere entre as revistas (de 5,7% a 58,1%). Identificamos quatro grupos estatisticamente distintos: História, Ciência, Saúde - Manguinhos (58% de artigos não citados); Physis: Revista de Saúde Coletiva, Interface, e Saúde e Sociedade (32% a 37%); Ciência & Saúde Coletiva e Revista Brasileira de Epidemiologia (16% a 17%); e Cadernos de Saúde Pública e Revista de Saúde Pública (6%). A não citação nos primeiros três anos pós-publicação também varia segundo revista. Quatro revistas mostraram claro declínio da não citação: Cadernos de Saúde Pública, Ciência & Saúde Coletiva, Revista Brasileira de Epidemiologia e Physis. Outras três (Revista de Saúde Pública, Saúde e Sociedade e Interface) apresentaram oscilação na não citação, mas as taxas de 2008 e 2012 são similares, com magnitudes diferentes. Por sua vez, a revista História, Ciência, Saúde - Manguinhos mantém taxas elevadas de não citação. Revistas multidisciplinares atraem mais citação, mas um modelo compreensivo de citações ainda precisa ser formulado e testado.

Tuberculous pyomyositis in an immunosuppressed patient.

Tuberculous pyomyositis is a rare manifestation of extrapulmonary tuberculosis, most common in immunosuppressed patients, with clinical manifestations similar to pyomyositis of other etiologies, although with a lower age of presentation; notable risk factors include prior tuberculosis infection and pharmacological immunosuppression. Diagnosis depends on a high clinical suspicion of the infection in a susceptible population, given that microbiological isolation is often impossible. The response to treatment and prognosis are good. The case presented here is noteworthy given the rarity of this manifestation of tuberculosis and the slow response to first-line TB management in an HIV patient, despite susceptible microbiological isolation.

Piomiositis tuberculosa en un paciente inmunosuprimido / Tuberculous pyomyositis in an immunosuppressed patient

La piomiositis tuberculosa es una manifestación poco frecuente de la tuberculosis extrapulmonar que se presenta más comúnmente en pacientes inmunosuprimidos, con manifestaciones clínicas similares a las de la piomiositis de otras etiologías, pero a una edad más temprana. Los factores de riesgo más usuales son la infección tuberculosa previa y la inmunosupresión farmacológica. El diagnóstico depende de la sospecha clínica en una población expuesta, ya que en muchas ocasiones el aislamiento microbiológico no es posible. La respuesta al tratamiento y el pronóstico son buenos. El caso que se presenta es llamativo dada la rareza de esta manifestación de la tuberculosis y la lenta mejoría con el tratamiento antituberculoso de primera línea en este paciente con infección por HIV y recaída, a pesar de que el aislamiento microbiológico resultó sensible.

Tuberculous pyomyositis is a rare manifestation of extrapulmonary tuberculosis, most common in immunosuppressed patients, with clinical manifestations similar to pyomyositis of other etiologies, although with a lower age of presentation; notable risk factors include prior tuberculosis infection and pharmacological immunosuppression. Diagnosis depends on a high clinical suspicion of the infection in a susceptible population, given that microbiological isolation is often impossible. The response to treatment and prognosis are good. The case presented here is noteworthy given the rarity of this manifestation of tuberculosis and the slow response to first-line TB management in an HIV patient, despite susceptible microbiological isolation.

A Detailed Characterization of the Dysfunctional Immunity and Abnormal Myelopoiesis Induced by Severe Shock and Trauma in the Aged.

The elderly are particularly susceptible to trauma, and their outcomes are frequently dismal. Such patients often have complicated clinical courses and ultimately die of infection and sepsis. Recent research has revealed that although elderly subjects have increased baseline inflammation as compared with their younger counterparts, the elderly do not respond to severe infection or injury with an exaggerated inflammatory response. Initial retrospective analysis of clinical data from the Glue Grant trauma database demonstrated that despite a similar frequency, elderly trauma patients have worse outcomes to pneumonia than younger subjects do. Subsequent analysis with a murine trauma model also demonstrated that elderly mice had increased mortality after posttrauma Pseudomonas pneumonia. Blood, bone marrow, and bronchoalveolar lavage sample analyses from juvenile and 20-24-mo-old mice showed that increased mortality to trauma combined with secondary infection in the aged are not due to an exaggerated inflammatory response. Rather, they are due to a failure of bone marrow progenitors, blood neutrophils, and bronchoalveolar lavage cells to initiate and complete an emergency myelopoietic response, engendering myeloid cells that fail to clear secondary infection. In addition, elderly people appeared unable to resolve their inflammatory response to severe injury effectively.

Clostridium difficile Infections after Blunt Trauma: A Different Patient Population?

BACKGROUND: The epidemiology of Clostridium difficile-associated infection (CDI) has changed, and it is evident that susceptibility is related not only to exposures and bacterial potency, but host factors as well. Several small studies have suggested that CDI after trauma is associated with a different patient phenotype. The purpose of this study was to examine and describe the epidemiologic factors associated with C. difficile in blunt trauma patients without traumatic brain injury using the Trauma-Related Database as a part of the "Inflammation and Host Response to Injury" (Glue Grant) and the University of Florida Integrated Data Repository. METHODS: Previously recorded baseline characteristics, clinical data, and outcomes were compared between groups (67 C. difficile and 384 uncomplicated, 813 intermediate, and 761 complicated non-C. difficile patients) as defined by the Glue Grant on admission and at days seven and 14. RESULTS: The majority of CDI patients experienced complicated or intermediate clinical courses. The mean ages of all cohorts were less than 65 y and CDI patients were significantly older than uncomplicated patients without CDI. The CDI patients had increased days in the hospital and on the ventilator, as well as significantly higher new injury severity scores (NISS), and a greater percentage of patients with NISS >34 points compared with non-CDI patients. They also had greater Marshall and Denver multiple organ dysfunction scores than non-CDI uncomplicated patients, and greater creatinine, alkaline phosphatase, neutrophil count, lactic acid, and PiO2:FiO2 compared with all non-CDI cohorts on admission. In addition, the CDI patients had higher glucose concentrations and base deficit from uncomplicated patients and greater leukocytosis than complicated patients on admission. Several of these changes persisted to days seven and 14. CONCLUSION: Analysis of severe blunt trauma patients with C. difficile, as compared with non-CDI patients, reveals evidence of increased inflammation, immunosuppression, worse acute kidney injury, higher NISS, greater days in the hospital and on the ventilator, higher organ injury scores, and prolonged clinical courses. This supports reports of an increased prevalence of CDI in a younger population not believed previously to be at risk. This unique population may have specific genomic or inflammation-related risk factors that may play more important roles in disease susceptibility. Prospective analysis may allow early identification of at-risk patients, creation of novel therapeutics, and improved understanding of how and why C. difficile colonization transforms into infection after severe blunt trauma.

Improved emergency myelopoiesis and survival in neonatal sepsis by caspase-1/11 ablation.

Over one million newborns die annually from sepsis with the highest mortality in premature and low-birthweight infants. The inflammasome plays a central role in the regulation of innate immunity and inflammation, and is presumed to be involved in protective immunity, in large part through the caspase-1-dependent activation of interleukin-1ß (IL-1ß) and IL-18. Studies in endotoxic shock, however, suggest that endogenous caspase-1 activity and the inflammasome contribute to mortality primarily by promoting excessive systemic inflammatory responses. We examined whether caspase-1 and the inflammasome also regulate neonatal inflammation, host protective immunity and myelopoiesis during polymicrobial sepsis. Neonatal (5-7 days) C57BL/6 and caspase-1/11(-/-) mice underwent a low-lethality caecal slurry model of intra-abdominal sepsis (LD25-45 ). Ablation of caspase-1/11, but not apoptosis-associated speck-like protein containing a CARD domain or nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), improved neonatal survival following septic challenge compared with wild-type mice (P < 0·001), with decreased concentrations of inflammatory cytokines in the serum and peritoneum. Surprisingly, caspase-1/11(-/-) neonates also exhibited increased bone marrow and splenic haematopoietic stem cell expansion (P < 0·001), and increased concentrations of granulocyte and macrophage colony-stimulating factors in the peritoneum (P < 0·001) after sepsis. Ablation of caspase-1/11 signalling was also associated with increased recruitment of peritoneal macrophages and neutrophils (P < 0·001), increased phagocytosis by neutrophils (P = 0·003), and decreased bacterial colonization (P = 0·02) in the peritoneum. These findings suggest that endogenous caspase-1/11 activity, independent of the NLRP3 inflammasome, not only promotes the magnitude of the inflammatory response, but also suppresses protective immunity in the neonate, so contributing to innate immune dysfunction and poor survival in neonatal sepsis.

TRIF-dependent innate immune activation is critical for survival to neonatal gram-negative sepsis.

Current evidence suggests that neonatal immunity is functionally distinct from adults. Although TLR signaling through the adaptor protein, MyD88, has been shown to be critical for survival to sepsis in adults, little is known about the role of MyD88 or TRIF in neonatal sepsis. We demonstrate that TRIF(-/-) but not MyD88(-/-) neonates are highly susceptible to Escherichia coli peritonitis and bacteremia. This was associated with decreased innate immune recruitment and function. Importantly, we found that the reverse was true in adults that MyD88(-/-) but not TRIF(-/-) or wild-type adults are susceptible to E. coli peritonitis and bacteremia. In addition, we demonstrate that TRIF but not MyD88 signaling is critical for the TLR4 protective adjuvant effect we have previously demonstrated. These data suggest a differential requirement for the survival of neonates versus adults to Gram-negative infection, and that modulation of TRIF in neonates can be used to augment survival to neonatal sepsis.

Delayed emergency myelopoiesis following polymicrobial sepsis in neonates.

Neonates have increased susceptibility to infection, which leads to increased mortality. Whether or not this as a result of implicit deficits in neonatal innate immune function or recapitulation of innate immune effector cell populations following infection is unknown. Here, we examine the process of emergency myelopoiesis whereby the host repopulates peripheral myeloid cells lost following the initial infectious insult. As early inflammatory responses are often dependent upon NF-κB and type I IFN signaling, we also examined whether the absence of MyD88, TRIF or MyD88 and TRIF signaling altered the myelopoietic response in neonates to polymicrobial sepsis. Following neonatal polymicrobial septic challenge, hematopoietic stem cell (HSC) expansion in bone marrow and the spleen were both attenuated and delayed in neonates compared with adults. Similar reductions in other precursors were observed in neonates. Similar to adult studies, the expansion of progenitor stem cell populations was also seen in the absence of MyD88 and/or TRIF signaling. Overall, neonates have impaired emergency myelopoiesis in response to sepsis compared with young adults. Despite reports that this expansion may be related to TLR signaling, our data suggest that other factors may be important, as TRIF(-/-) and MyD88(-/-) neonatal HSCs are still able to expand in response to polymicrobial neonatal sepsis.

Novel role for tumor-induced expansion of myeloid-derived cells in cancer cachexia.

Cancer progression is associated with inflammation, increased metabolic demand, infection, cachexia, and eventually death. Myeloid-derived suppressor cells (MDSCs) commonly expand during cancer and are associated with adaptive immune suppression and inflammatory metabolite production. We propose that cancer-induced cachexia is driven at least in part by the expansion of MDSCs. MDSC expansion in 4T1 mammary carcinoma-bearing hosts is associated with induction of a hepatic acute-phase protein response and altered host energy and fat metabolism, and eventually reduced survival to polymicrobial sepsis and endotoxemia. Similar results are also seen in mice bearing a Lewis lung carcinoma and a C26 colon adenocarcinoma. However, a similar cachexia response is not seen with equivalent growth of the 66C4 subclone of 4T1, in which MDSC expansion does not occur. Importantly, reducing MDSC numbers in 4T1-bearing animals can ameliorate some of these late responses and reduce susceptibility to inflammation-induced organ injury and death. In addition, administering MDSCs from both tumor- and nontumor-bearing mice can produce an acute-phase response. Thus, we propose a previously undescribed mechanism for the development of cancer cachexia, whereby progressive MDSC expansion contributes to changes in host protein and energy metabolism and reduced resistance to infection.

Host responses to sepsis vary in different low-lethality murine models.

INTRODUCTION: Animal models for the study of sepsis are being increasingly scrutinized, despite their essential role for early translational research. In particular, recent studies have suggested that at the level of the leukocyte transcriptome, murine models of burns, trauma and endotoxemia markedly differ from their human equivalents, and are only weakly similar amongst themselves. We compared the plasma cytokine and leukocyte transcriptome responses between two different low-lethality murine models of polymicrobial intra-abdominal sepsis. METHODS: Six to ten week male C57BL/6j mice underwent either the 'gold standard' cecal ligation and puncture (CLP) model of intra-abdominal sepsis or administration of a cecal slurry (CS), where cecal contents are injected intraperitoneally. Surviving mice were euthanized at two hours, one or three days after sepsis. RESULTS: The murine leukocyte transcriptomic response to the CLP and CS models of sepsis was surprisingly dissimilar at two hours, one, and three days after sepsis. The Pearson correlation coefficient for the maximum change in expression for the entire leukocyte transcriptome that changed significantly over time (n = 19,071) was R = 0.54 (R2 = 0.297). The CS model resulted in greater magnitude of early inflammatory gene expression changes in response to sepsis with associated increased production of inflammatory chemokines and cytokines. Two hours after sepsis, CLP had more significant expression of genes associated with IL-10 signaling pathways, whereas CS had greater expression of genes related to CD28, apoptosis, IL-1 and T-cell receptor signaling. By three days, the changes in gene expression in both sepsis models were returning to baseline in surviving animals. CONCLUSION: These analyses reveal that the murine blood leukocyte response to sepsis is highly dependent on which model of intra-abdominal sepsis is employed, despite their similar lethality. It may be difficult to extrapolate findings from one murine model to another, let alone to human sepsis.

Protective immunity and defects in the neonatal and elderly immune response to sepsis.

Populations encompassing extremes of age, including neonates and elderly, have greater mortality from sepsis. We propose that the increased mortality observed in the neonatal and elderly populations after sepsis is due to fundamental differences in host-protective immunity and is manifested at the level of the leukocyte transcriptome. Neonatal (5-7 d), young adult (6-12 wk), or elderly (20-24 mo) mice underwent a cecal slurry model of intra-abdominal sepsis. Both neonatal and elderly mice exhibited significantly greater mortality to sepsis (p < 0.05). Neonates in particular exhibited significant attenuation of their inflammatory response (p < 0.05), as well as reductions in cell recruitment and reactive oxygen species production (both p < 0.05), all of which could be confirmed at the level of the leukocyte transcriptome. In contrast, elderly mice were also more susceptible to abdominal peritonitis, but this was associated with no significant differences in the magnitude of the inflammatory response, reduced bacterial killing (p < 0.05), reduced early myeloid cell activation (p < 0.05), and a persistent inflammatory response that failed to resolve. Interestingly, elderly mice expressed a persistent inflammatory and immunosuppressive response at the level of the leukocyte transcriptome, with failure to return to baseline by 3 d. This study reveals that neonatal and elderly mice have profoundly different responses to sepsis that are manifested at the level of their circulating leukocyte transcriptome, although the net result of increased mortality is similar. Considering these differences are fundamental aspects of the genomic response to sepsis, interventional therapies will require individualization based on the age of the population.

A better understanding of why murine models of trauma do not recapitulate the human syndrome.

OBJECTIVE: Genomic analyses from blood leukocytes have concluded that mouse injury poorly reflects human trauma at the leukocyte transcriptome. Concerns have focused on the modest severity of murine injury models, differences in murine compared with human age, dissimilar circulating leukocyte populations between species, and whether similar signaling pathways are involved. We sought to examine whether the transcriptomic response to severe trauma in mice could be explained by these extrinsic factors, by utilizing an increasing severity of murine trauma and shock in young and aged mice over time, and by examining the response in isolated neutrophil populations. DESIGN: Preclinical controlled in vivo laboratory study and retrospective cohort study. SETTING: Laboratory of Inflammation Biology and Surgical Science and multi-institution level 1 trauma centers. SUBJECTS: Six- to 10-week-old and 20- to 24-month-old C57BL/6 (B6) mice and two cohorts of 167 and 244 severely traumatized (Injury Severity Score > 15) adult (> 18 yr) patients. INTERVENTIONS: Mice underwent one of two severity polytrauma models of injury. Total blood leukocyte and neutrophil samples were collected. MEASUREMENTS AND MAIN RESULTS: Fold expression changes in leukocyte and neutrophil genome-wide expression analyses between healthy and injured mice (p < 0.001) were compared with human total and enriched blood leukocyte expression analyses of severe trauma patients at 0.5, 1, 4, 7, 14, and 28 days after injury (Glue Grant trauma-related database). We found that increasing the severity of the murine trauma model only modestly improved the correlation in the transcriptomic response with humans, whereas the age of the mice did not. In addition, the genome-wide response to blood neutrophils (rather than total WBC) was also not well correlated between humans and mice. However, the expression of many individual gene families was much more strongly correlated after injury in mice and humans. CONCLUSIONS: Although overall transcriptomic association remained weak even after adjusting for the severity of injury, age of the animals, timing, and individual leukocyte populations, there were individual signaling pathways and ontogenies that were strongly correlated between mice and humans. These genes are involved in early inflammation and innate/adaptive immunity.

Aged mice are unable to mount an effective myeloid response to sepsis.

The elderly have increased morbidity and mortality following sepsis; however, the cause(s) remains unclear. We hypothesized that these poor outcomes are due in part to defects in innate immunity, rather than to an exaggerated early inflammatory response. Young (6-12 wk) or aged (20-24 mo) mice underwent polymicrobial sepsis, and subsequently, the aged mice had increased mortality and defective peritoneal bacterial clearance compared with young mice. No differences were found in the magnitude of the plasma cytokine responses. Although septic aged mice displayed equivalent or increased numbers of circulating, splenic, and bone marrow myeloid cells, some of these cells exhibited decreased phagocytosis, reactive oxygen species production, and chemotaxis. Blood leukocyte gene expression was less altered in aged versus young mice 1 d after sepsis. Aged mice had a relative inability to upregulate gene expression of pathways related to neutrophil-mediated protective immunity, chemokine/chemokine receptor binding, and responses to exogenous molecules. Expression of most MHC genes remained more downregulated in aged mice at day 3. Despite their increased myeloid response to sepsis, the increased susceptibility of aged mice to sepsis appears not to be due to an exaggerated inflammatory response, but rather, a failure to mount an effective innate immune response.