Construction and Validation of an Occupational Risks Scale for Intra-hospital Nursing Staff / Construcción y validación de una escala de riesgos laborales del personal de enfermería intrahospitalario / Construção e validação de escala de risco ocupacional para equipe de enfermagem intra-hospitalar

Objective. To construct and evaluate initial validity indicators of an instrument on occupational risks for hospital nursing staff. Methods. A methodological study was conducted in four Chilean hospitals. The study was carried out in three stages: (i) integrative literature review on risk assessment instruments for nursing; (ii) descriptive qualitative study on 113 health professionals to identify their work conditions and experiences regarding occupational risks and construct three instruments proposals for nursing managers, clinical nurses, and technicians; and (iii) validity and reliability study of the three instruments in 503 nurses and nursing technicians. To collect the data from the qualitative study, individual interviews, focal groups, and non-participant observation were conducted. The data were analyzed thematically into predefined risk categories. Content validation was performed through expert judgment, and exploratory factor analysis of principal components was conducted for the preliminary construct validity study. Cronbach's alpha was used as an indicator of internal consistency. Results. A total of 128 items were identified, distributed across 11 categories and 25 subcategories of occupational risks for the three instruments derived from the original proposal. After expert validation, pilot study, and instrument administration, Cronbach's alpha values between 0.88 and 0.93 were obtained. Exploratory factor analysis distinguished eight to eleven components, with unsatisfactory goodness-of-fit indicators. Conclusion. The instruments demonstrated good parameters of content validity and reliability, although their construct validity needs further improvement.

Objetivo. Construir y evaluar indicadores de validez inicial de un instrumento sobre riesgos laborales del personal de enfermería intrahospitalario. Métodos.Estudio metodológico, participaron cuatro hospitales chilenos. Se desarrolló en tres etapas: (i) revisión integradora de la literatura sobre instrumentos de evaluación de riesgos en enfermería; (ii) estudio cualitativo descriptivo en 113 profesionales de salud para identificar sus condiciones laborales y vivencias respecto a los riesgos laborales y construir tres propuestas de instrumentos para jefaturas de enfermería, enfermeros clínicos y técnicos; y (iii) estudio de validez y confiabilidad de los tres instrumentos en 503 enfermeros y técnicos en enfermería. Para la recolección de datos del estudio cualitativo se realizaron entrevistas individuales, grupos focales y observación no participante. Los datos fueron analizados temáticamente en categorías de riesgos predefinidas. La validación de contenido se realizó a través del juicio de expertos y para el estudio preliminar de validez de constructo se hizo análisis factorial exploratorio de componentes principales. Como indicador de la consistencia interna se aplicó Alfa de Cronbach. Resultados. Se identificaron 128 ítems para 11 categorías y 25 subcategorías de riesgos laborales para tres instrumentos derivados del originalmente propuesto. Luego de la validación por expertos, el estudio piloto y la aplicación de los instrumentos, se obtuvieron valores alfa de Cronbach entre 0.88 y 0.93. El análisis factorial exploratorio distinguió ocho a once componentes, no lográndose buenos indicadores de bondad de ajuste. Conclusión. Los instrumentos presentan buenos parámetros de validez de contenido y confiabilidad, debiéndose perfeccionar su validez de constructo.

Objetivo. Construir e avaliar indicadores de validade inicial de um instrumento sobre riscos ocupacionais da equipe de enfermagem intra-hospitalar. Métodos. Estudo metodológico, quatro hospitais chilenos participaram. Foi desenvolvido em três etapas: (i) revisão integrativa da literatura sobre instrumentos de avaliação de risco em enfermagem; (ii) estudo descritivo qualitativo em 113 profissionais de saúde para identificar suas condições de trabalho e experiências em relação aos riscos ocupacionais e construir três propostas de instrumentos para chefes, enfermeiros assistenciais e técnicos de enfermagem; e (iii) estudo de validade e confiabilidade dos três instrumentos em 503 enfermeiros e técnicos de enfermagem. Para a coleta de dados do estudo qualitativo, foram realizadas entrevistas individuais, grupos focais e observação não participante. Os dados foram analisados tematicamente em categorias de risco pré-definidas. A validação de conteúdo foi realizada por meio de julgamento de especialistas e para o estudo preliminar de validade de construto foi realizada uma análise fatorial exploratória de componentes principais. Como indicador de consistência interna, foi aplicado o Alfa de Cronbach. Resultados. Foram identificados 128 itens para 11 categorias e 25 subcategorias de riscos ocupacionais para três instrumentos derivados do originalmente proposto. Após a validação por especialistas, o estudo piloto e a aplicação dos instrumentos, foram obtidos valores de alfa de Cronbach entre 0.88 e 0.93. A análise fatorial exploratória distinguiu de oito a onze componentes, não alcançando bons indicadores de qualidade de ajuste. Conclusão. Os instrumentos apresentam bons parâmetros de validade de conteúdo e confiabilidade, e sua validade de construto deve ser aprimorada.

Construction and Validation of an Occupational Risks Scale for Intra-hospital Nursing Staff.

Objective: To construct and evaluate initial validity indicators of an instrument on occupational risks for hospital nursing staff. Methods: A methodological study was conducted in four Chilean hospitals. The study was carried out in three stages: (i) integrative literature review on risk assessment instruments for nursing; (ii) descriptive qualitative study on 113 health professionals to identify their work conditions and experiences regarding occupational risks and construct three instruments proposals for nursing managers, clinical nurses, and technicians; and (iii) validity and reliability study of the three instruments in 503 nurses and nursing technicians. To collect the data from the qualitative study, individual interviews, focal groups, and non-participant observation were conducted. The data were analyzed thematically into predefined risk categories. Content validation was performed through expert judgment, and exploratory factor analysis of principal components was conducted for the preliminary construct validity study. Cronbach's alpha was used as an indicator of internal consistency. Results: A total of 128 items were identified, distributed across 11 categories and 25 subcategories of occupational risks for the three instruments derived from the original proposal. After expert validation, pilot study, and instrument administration, Cronbach's alpha values between 0.88 and 0.93 were obtained. Exploratory factor analysis distinguished eight to eleven components, with unsatisfactory goodness-of-fit indicators. Conclusion: The instruments demonstrated good parameters of content validity and reliability, although their construct validity needs further improvement.

[Statistical literacy and risk communication for COVID-19 vaccination: a scoping reviewLiteracia estatística e comunicação de risco para a vacinação contra a COVID-19: revisão de escopo]. / Alfabetización estadística y comunicación de riesgo para la vacunación contra la COVID-19: una revisión de alcance.

OBJECTIVE: To describe the role of statistical literacy and proper risk communication in communication strategies related to COVID-19 vaccination. METHODS: A scoping review was carried out in January 2021, with the keywords "statistical literacy," "risk communication," "health communication," and "pandemic," in the Pan American Health Organization Virtual Health Library, PubMed, Web of Science, EBSCO, and Google Scholar databases. No filters were applied for dates, language, or publication type. RESULTS: Of the 87 articles identified, four met the inclusion criteria. Four main messages were recognized that relate statistical literacy and risk communication: 1) risk communication and statistical literacy level affect individual and collective decision-making; 2) communication of uncertainty should include what is known and not known with regard to statistics and risks; 3) the use of graphics and visuals is key to appropriately informing the population; and 4) different formats should be used to improve communication, always adjusted to the population's statistical literacy level. CONCLUSIONS: Statistical literacy plays a key role in communicating risks related to health in general and COVID-19 vaccination in particular. In health emergencies, proper communication of risk and associated uncertainty should be clear, transparent, and timely.

OBJETIVO: Descrever o papel da literacia estatística e da comunicação correta de riscos nas estratégias de comunicação relacionadas à vacinação contra a COVID-19. MÉTODOS: Em janeiro de 2021, foi realizada uma revisão de escopo com as palavras-chave "statistical literacy", "risk communication", "health communication" e "pandemic" nos bancos de dados da Biblioteca Virtual em Saúde da Organização Pan-Americana da Saúde, PubMed, Web of Science, EBSCO e Google Scholar. Não foi aplicado filtro de data, idioma ou tipo de publicação. RESULTADOS: Dos 87 artigos identificados, quatro atenderam aos critérios de inclusão. Foram reconhecidas quatro mensagens principais relacionadas à literacia estatística e à comunicação de risco: 1) a comunicação de risco e o nível de literacia estatística afetam a tomada de decisão individual e coletiva; 2) a comunicação da incerteza deve incluir o que é conhecido e desconhecido sobre estatísticas e riscos; 3) o uso de gráficos e visualizações é fundamental para informar adequadamente a população; e 4) devem ser usados diferentes formatos para melhorar a comunicação, sempre ajustados ao nível de literacia estatística da população. CONCLUSÕES: A literacia estatística desempenha um papel fundamental na comunicação dos riscos relacionados à saúde em geral e à vacinação contra a COVID-19 em particular. Em situações de emergência de saúde, a comunicação correta do risco e da incerteza a ele associada deve ser clara, transparente e oportuna.

Alfabetización estadística y comunicación de riesgo para la vacunación contra la COVID-19: una revisión de alcance

[RESUMEN]. Objetivo. Describir el papel que desempeñan la alfabetización estadística y la correcta comunicación de riesgo en las estrategias de comunicación relacionadas con la vacunación contra la COVID-19. Métodos. Se realizó una revisión de alcance en enero del 2021, con las palabras clave “ statistical literacy ”, “ risk communication”, “health communication ” y “ pandemic ” en las bases de datos de la Biblioteca Virtual en Salud de la Organización Panamericana de la Salud, PubMed, Web of Science, EBSCO y Google Académico. No se aplicaron filtros para fechas, idioma o tipos de publicación. Resultados. De los 87 artículos identificados, cuatro cumplieron con los criterios de inclusión. Se recono-cieron cuatro mensajes principales que relacionan la alfabetización estadística y la comunicación de riesgo: 1) la comunicación de riesgo y el nivel de alfabetización estadística afectan a la toma de decisión individual y colectiva, 2) la comunicación de la incertidumbre debe incluir lo que se sabe y no se sabe respecto a las estadísticas y los riesgos, 3) el uso de gráficos y visualizaciones es clave para informar apropiadamente a la población y 4) deben utilizarse diferentes formatos para mejorar la comunicación, siempre ajustados al nivel de alfabetización estadística de la población. Conclusiones. La alfabetización estadística desempeña un papel clave en la comunicación de los riesgos relacionados con la salud en general y la vacunación contra la COVID-19 en particular. En situaciones de emergencia sanitaria, la correcta comunicación de riesgo y de la incertidumbre asociada debe ser clara, transparente y oportuna.

[ABSTRACT]. Objective. To describe the role of statistical literacy and proper risk communication in communication strate-gies related to COVID-19 vaccination.Methods. A scoping review was carried out in January 2021, with the keywords “statistical literacy,” “risk com-munication,” “health communication,” and “pandemic,” in the Pan American Health Organization Virtual Health Library, PubMed, Web of Science, EBSCO, and Google Scholar databases. No filters were applied for dates, language, or publication type.Results. Of the 87 articles identified, four met the inclusion criteria. Four main messages were recognized that relate statistical literacy and risk communication: 1) risk communication and statistical literacy level affect indi-vidual and collective decision-making; 2) communication of uncertainty should include what is known and not known with regard to statistics and risks; 3) the use of graphics and visuals is key to appropriately informing the population; and 4) different formats should be used to improve communication, always adjusted to the population’s statistical literacy level.Conclusions. Statistical literacy plays a key role in communicating risks related to health in general and COVID-19 vaccination in particular. In health emergencies, proper communication of risk and associated uncertainty should be clear, transparent, and timely.

[RESUMO]. Objetivo. Descrever o papel da literacia estatística e da comunicação correta de riscos nas estratégias de comunicação relacionadas à vacinação contra a COVID-19.Métodos. Em janeiro de 2021, foi realizada uma revisão de escopo com as palavras-chave “statistical lite-racy”, “risk communication”, “health communication” e “pandemic” nos bancos de dados da Biblioteca Virtual em Saúde da Organização Pan-Americana da Saúde, PubMed, Web of Science, EBSCO e Google Scholar. Não foi aplicado filtro de data, idioma ou tipo de publicação.Resultados. Dos 87 artigos identificados, quatro atenderam aos critérios de inclusão. Foram reconhecidas quatro mensagens principais relacionadas à literacia estatística e à comunicação de risco: 1) a comunicação de risco e o nível de literacia estatística afetam a tomada de decisão individual e coletiva; 2) a comunicação da incerteza deve incluir o que é conhecido e desconhecido sobre estatísticas e riscos; 3) o uso de gráficos e visualizações é fundamental para informar adequadamente a população; e 4) devem ser usados diferentes formatos para melhorar a comunicação, sempre ajustados ao nível de literacia estatística da população.Conclusões. A literacia estatística desempenha um papel fundamental na comunicação dos riscos relaciona-dos à saúde em geral e à vacinação contra a COVID-19 em particular. Em situações de emergência de saúde, a comunicação correta do risco e da incerteza a ele associada deve ser clara, transparente e oportuna.

Transport modes and road traffic mortality in the Americas: Deaths among pedestrian and motorcycle users through the lifespan.

INTRODUCTION: In the Americas, almost half of road traffic deaths occur among motorcycle users and pedestrians (23% and 22%, respectively). Recent individual country trends show that nations are experiencing changes in deaths depending on the mode of transport used. While national trends are useful, analyses of disaggregated data by sex and age may provide more information about the impact of traffic crashes at different stages of the life course. Methods: We used mortality data from all land transport modes reported to PAHO/WHO (2000-2015) and included them in an ecological study to quantify temporal trends and estimate the association between mortality by mode, age group, sex, and selected socio-economic indicators. Results: Motorcycle and pedestrian mortality rates remain extremely high. Males younger less than 45 years have a higher burden of motorcycle-related mortality while older persons tend to die more as pedestrians. Discussion: Policies differentially aimed at addressing deaths by mode of transport and age are necessary because active living improves wellbeing especially among older individuals. For this to occur, safe environments must be created or maintained.

Valor de la resonancia magnética cardíaca para el diagnóstico diferencial en pacientes con sospecha de infarto agudo de miocardio con elevación del segmento ST y arterias coronarias normales

Background: Patients hospitalized with suspected ST-segment elevation myocardial infarction (STEMI) who have normal coronary arteries (CAs) on invasive coronary angiography (ICA) may have an AMI or another acute cardiac disease that mimics it. Aim: To evaluate the usefulness of cardiac magnetic resonance imaging (CMRI) for diagnosing conditions resembling AMI with normal CAs. Material and Methods: We studied 424 consecutive patients admitted with suspected STEMI who underwent ICA. Those with normal CAs underwent CMRI involving cine-CMRI sequences to evaluate segmental wall motion, T2-weighted short-tau inversion-recovery imaging to detect oedema and delayed contrast enhancement (DCE) after gadolinium administration to identify necrosis/fibrosis. Patients with previous myocardial infarction were excluded. Results: Twenty-six patients (6.1%) had normal CAs. Definitive diagnosis after CMRI was acute myocarditis in 11 patients (42.3%) whose DCE was localized in the subepicardium or intramyocardially but not in the endocardium, AMI in nine patients (34.6%) who had subendocardial or transmural DCE, and Takotsubo cardiomyopathy (TCM) in six patients (23.1%), whose CMRI showed regional contractility abnormalities of the left ventricle and myocardial oedema but not DCE. Conclusions: Cardiac magnetic resonance imaging allows a precise diagnosis of acute myocardial infarction in patients with angiographically normal coronary arteries.

[Cardiac magnetic resonance imaging in patients with a suspected myocardial infarction and normal coronary arteries]. / Valor de la resonancia magnética cardíaca para el diagnóstico diferencial en pacientes con sospecha de infarto agudo de miocardio con elevación del segmento ST y arterias coronarias normales.

BACKGROUND: Patients hospitalized with suspected ST-segment elevation myocardial infarction (STEMI) who have normal coronary arteries (CAs) on invasive coronary angiography (ICA) may have an AMI or another acute cardiac disease that mimics it. AIM: To evaluate the usefulness of cardiac magnetic resonance imaging (CMRI) for diagnosing conditions resembling AMI with normal CAs. MATERIAL AND METHODS: We studied 424 consecutive patients admitted with suspected STEMI who underwent ICA. Those with normal CAs underwent CMRI involving cine-CMRI sequences to evaluate segmental wall motion, T2-weighted short-tau inversion-recovery imaging to detect oedema and delayed contrast enhancement (DCE) after gadolinium administration to identify necrosis/fibrosis. Patients with previous myocardial infarction were excluded. RESULTS: Twenty-six patients (6.1%) had normal CAs. Definitive diagnosis after CMRI was acute myocarditis in 11 patients (42.3%) whose DCE was localized in the subepicardium or intramyocardially but not in the endocardium, AMI in nine patients (34.6%) who had subendocardial or transmural DCE, and Takotsubo cardiomyopathy (TCM) in six patients (23.1%), whose CMRI showed regional contractility abnormalities of the left ventricle and myocardial oedema but not DCE. CONCLUSIONS: Cardiac magnetic resonance imaging allows a precise diagnosis of acute myocardial infarction in patients with angiographically normal coronary arteries.

Epanorin, a lichen secondary metabolite, inhibits proliferation of MCF-7 breast cancer cells.

BACKGROUND: Epanorin (EP) is a secondary metabolite of the Acarospora lichenic species. EP has been found in lichenic extracts with antimicrobial activity, and UV-absorption properties have been described for closely related molecules; however, its antiproliferative activity in cancer cells has not yet been explored. It has been hypothesized that EP inhibits cancer cell growth. MCF-7 breast cancer cells, normal fibroblasts, and the non-transformed HEK-293 cell line were exposed to increasing concentrations of EP, and proliferation was assessed by the sulforhodamine-B assay. RESULTS: MCF-7 cells exposed to EP were examined for cell cycle progression using flow cytometry, and DNA fragmentation was examined using the TUNEL assay. In addition, EP's mutagenic activity was assessed using the Salmonella typhimurium reverse mutation assay. The data showed that EP inhibits proliferation of MCF-7 cells, and it induces cell cycle arrest in G0/G1 through a DNA fragmentation-independent mechanism. Furthermore, EP's lack of overt cytotoxicity in the normal cell line HEK-293 and human fibroblasts in cell culture is supported by the absence of mutagenic activity of EP. CONCLUSION: EP emerges as a suitable molecule for further studies as a potential antineoplastic agent.

Epanorin, a lichen secondary metabolite, inhibits proliferation of MCF-7 breast cancer cells

BACKGROUND: Epanorin (EP) is a secondary metabolite of the Acarospora lichenic species. EP has been found in lichenic extracts with antimicrobial activity, and UV-absorption properties have been described for closely related molecules; however, its antiproliferative activity in cancer cells has not yet been explored. It has been hypothesized that EP inhibits cancer cell growth. MCF-7 breast cancer cells, normal fibroblasts, and the non-transformed HEK-293 cell line were exposed to increasing concentrations of EP, and proliferation was assessed by the sulforhodamine-B assay. RESULTS: MCF-7 cells exposed to EP were examined for cell cycle progression using flow cytometry, and DNA fragmentation was examined using the TUNEL assay. In addition, EP's mutagenic activity was assessed using the Salmonella typhimurium reverse mutation assay. The data showed that EP inhibits proliferation of MCF-7 cells, and it induces cell cycle arrest in G0/G1 through a DNA fragmentation-independent mechanism. Furthermore, EP's lack of overt cytotoxicity in the normal cell line HEK-293 and human fibroblasts in cell culture is supported by the absence of mutagenic activity of EP. CONCLUSION: EP emerges as a suitable molecule for further studies as a potential antineoplastic agent.

Patient Safety Incidents and Nursing Workload.

Objective: to identify the relationship between the workload of the nursing team and the occurrence of patient safety incidents linked to nursing care in a public hospital in Chile. Method: quantitative, analytical, cross-sectional research through review of medical records. The estimation of workload in Intensive Care Units (ICUs) was performed using the Therapeutic Interventions Scoring System (TISS-28) and for the other services, we used the nurse/patient and nursing assistant/patient ratios. Descriptive univariate and multivariate analysis were performed. For the multivariate analysis we used principal component analysis and Pearson correlation. Results: 879 post-discharge clinical records and the workload of 85 nurses and 157 nursing assistants were analyzed. The overall incident rate was 71.1%. It was found a high positive correlation between variables workload (r = 0.9611 to r = 0.9919) and rate of falls (r = 0.8770). The medication error rates, mechanical containment incidents and self-removal of invasive devices were not correlated with the workload. Conclusions: the workload was high in all units except the intermediate care unit. Only the rate of falls was associated with the workload.

Patient Safety Incidents and Nursing Workload / Ocorrência de incidentes de Segurança do Paciente e Carga de Trabalho de Enfermagem / Ocurrencia de Incidentes de Seguridad del Paciente y Carga de Trabajo de Enfermería

ABSTRACT Objective: to identify the relationship between the workload of the nursing team and the occurrence of patient safety incidents linked to nursing care in a public hospital in Chile. Method: quantitative, analytical, cross-sectional research through review of medical records. The estimation of workload in Intensive Care Units (ICUs) was performed using the Therapeutic Interventions Scoring System (TISS-28) and for the other services, we used the nurse/patient and nursing assistant/patient ratios. Descriptive univariate and multivariate analysis were performed. For the multivariate analysis we used principal component analysis and Pearson correlation. Results: 879 post-discharge clinical records and the workload of 85 nurses and 157 nursing assistants were analyzed. The overall incident rate was 71.1%. It was found a high positive correlation between variables workload (r = 0.9611 to r = 0.9919) and rate of falls (r = 0.8770). The medication error rates, mechanical containment incidents and self-removal of invasive devices were not correlated with the workload. Conclusions: the workload was high in all units except the intermediate care unit. Only the rate of falls was associated with the workload.

RESUMO Objetivo: identificar a relação entre a carga de trabalho da equipe de enfermagem e a ocorrência de incidentes de segurança dos pacientes ligados aos cuidados de enfermagem de um hospital público no Chile. Método: pesquisa transversal analítica quantitativa através de revisão de prontuários médicos. A estimativa da carga de trabalho em Unidade de Terapia Intensiva (UTI) foi realizada utilizando o Índice de Intervenções Terapêuticas-TISS-28 e para os outros serviços, foram utilizados os cocientes enfermeira/paciente e auxiliar de enfermagem/ paciente. Foram feitas análises univariada descritiva e multivariada. Para a análise multivariada utilizou-se análise de componentes principais e correlação de Pearson. Resultados: foram analisados 879 prontuáriosclínicos de pós-alta e a carga de trabalho de 85 enfermeiros e 157 auxiliares de enfermagem. A taxa global de incidentes foi de 71,1%. Foi encontrada uma alta correlação positiva entre as variáveis de carga de trabalho (r = 0,9611 para r = 0,9919) e a taxa de quedas (r = 0,8770). As taxas de erro de medicação, incidentes de contenção mecânica e auto remoção de dispositivos invasivos não foram correlacionadas com a carga de trabalho. Conclusões: a carga de trabalho foi elevada em todas as unidades, exceto na unidade de cuidados intermédios. Apenas a taxa de quedas foi associada com a carga de trabalho.

RESUMEN Objetivo: identificar la relación entre la carga laboral del equipo de enfermería y la ocurrencia de incidentes de seguridad del paciente relacionados con los cuidados de enfermería en un hospital público de Chile. Método: investigación cuantitativa, analítica, transversal, realizada por revisión de fichas clínicas. La estimación de carga laboral en las Unidades de Cuidados Intensivos (UCI) se realizó utilizando el Índice de Intervenciones Terapéuticas (TISS-28) y, para el resto de los servicios, por la relación enfermera/paciente y auxiliar/paciente. Se realizó análisis descriptivo univariado y multivariado. Para el análisis multivariado se utilizó análisis de componentes principales y el test de correlación de Pearson. Resultados: se revisaron 879 fichas clínicas posteriores al alta y la carga laboral de 85 enfermeras y 157 auxiliares de enfermería. La tasa global de incidentes fue 71,1%. Se encontró correlación positiva alta entre las variables de carga laboral (r = 0,9611 a r = 0,9919) y tasa de caídas (r = 0,8770). Las tasas de error de medicación, incidente por contención mecánica y auto retiro de invasivos no se correlacionaron con la carga laboral. Conclusiones: la carga laboral fue elevada en todas las unidades a excepción de la unidad de cuidados intermedios. Sólo la tasa de caídas se asoció a la carga laboral.

The effect of an autologous cellular gel-matrix integrated implant system on wound healing.

BACKGROUND: This manuscript reports the production and preclinical studies to examine the tolerance and efficacy of an autologous cellular gel-matrix integrated implant system (IIS) aimed to treat full-thickness skin lesions. METHODS: The best concentration of fibrinogen and thrombin was experimentally determined by employing 28 formula ratios of thrombin and fibrinogen and checking clot formation and apparent stability. IIS was formed by integrating skin cells by means of the in situ gelification of fibrin into a porous crosslinked scaffold composed of chitosan, gelatin and hyaluronic acid. The in vitro cell proliferation within the IIS was examined by the MTT assay and PCNA expression. An experimental rabbit model consisting of six circular lesions was utilized to test each of the components of the IIS. Then, the IIS was utilized in an animal model to cover a 35% body surface full thickness lesion. RESULTS: The preclinical assays in rabbits demonstrated that the IIS was well tolerated and also that IIS-treated rabbit with lesions of 35% of their body surface, exhibited a better survival rate (p = 0,06). CONCLUSION: IIS should be further studied as a new wound dressing which shows promising properties, being the most remarkable its good biological tolerance and cell growth promotion properties.

Urban air pollution: influences on olfactory function and pathology in exposed children and young adults.

Mexico City (MC) residents are exposed to severe air pollution and exhibit olfactory bulb inflammation. We compared the olfactory function of individuals living under conditions of extreme air pollution to that of controls from a relatively clean environment and explore associations between olfaction scores, apolipoprotein E (APOE) status, and pollution exposure. The olfactory bulbs (OBs) of 35 MC and 9 controls 20.8+/-8.5 years were assessed by light and electron microscopy. The University of Pennsylvania Smell Identification Test (UPSIT) was administered to 62 MC/25 controls 21.2+/-2.7 years. MC subjects had significantly lower UPSIT scores: 34.24+/-0.42 versus controls 35.76+/-0.40, p=0.03. Olfaction deficits were present in 35.5% MC and 12% of controls. MC APOE epsilon 4 carriers failed 2.4+/-0.54 items in the 10-item smell identification scale from the UPSIT related to Alzheimer's disease, while APOE 2/3 and 3/3 subjects failed 1.36+/-0.16 items, p=0.01. MC residents exhibited OB endothelial hyperplasia, neuronal accumulation of particles (2/35), and immunoreactivity to beta amyloid betaA(42) (29/35) and/or alpha-synuclein (4/35) in neurons, glial cells and/or blood vessels. Ultrafine particles were present in OBs endothelial cytoplasm and basement membranes. Control OBs were unremarkable. Air pollution exposure is associated with olfactory dysfunction and OB pathology, APOE 4 may confer greater susceptibility to such abnormalities, and ultrafine particles could play a key role in the OB pathology. This study contributes to our understanding of the influences of air pollution on olfaction and its potential contribution to neurodegeneration.

Effects of a cyclooxygenase-2 preferential inhibitor in young healthy dogs exposed to air pollution: a pilot study.

Residency in cities with high air pollution is associated with neuroinflammation and neurodegeneration in healthy children, young adults, and dogs. Nonsteroidal anti-inflammatory drugs may offer neuroprotection. The authors measured the plasma concentrations of 3-nitrotyrosine and the cerebro-spinal-fluid concentrations of prostaglandin E2 metabolite and the oligomeric form of amyloid derived diffusible ligand; measured the mRNA expression of cyclooxygenase-2, interleukin 1beta, CD14, and Aquaporin-4 in target brain areas; and evaluated brain MRI, cognition, and neuropathology in 8 dogs treated with a preferential cyclooxygenase-2 inhibitor (Nimesulide) versus 7 untreated litter-matched Mexico City dogs. Nimesulide significantly decreased nitrotyrosine in plasma (p < .0001), frontal gray IL1beta (p = .03), and heart IL1beta (p = .02). No effect was seen in mRNA COX2, amyloid, and PGE2 in CSF or the MRI white matter lesions. All exposed dogs exhibited olfactory bulb and frontal accumulation of Abeta(42) in neurons and blood vessels and frontal vascular subcortical pathology. White matter hyperintense MRI frontal lesions were seen in 4/6 non-treated and 6/8 treated dogs. Nonsteroidal anti-inflammatory drugs may offer limited neuroprotection in the setting of severe air pollution exposures. The search for potentially beneficial drugs useful to ameliorate the brain effects of pollution represents an enormous clinical challenge.

Immunotoxicity and environment: immunodysregulation and systemic inflammation in children.

Environmental pollutants, chemicals, and drugs have an impact on children's immune system development. Mexico City (MC) children exposed to significant concentrations of air pollutants exhibit chronic respiratory inflammation, systemic inflammation, neuroinflammation, and cognitive deficits. We tested the hypothesis that exposure to severe air pollution plays a role in the immune responses of asymptomatic, apparently healthy children. Blood measurements for markers of immune function, inflammatory mediators, and molecules interacting with the lipopolysaccharide recognition complex were obtained from two cohorts of matched children (aged 9.7 +/- 1.2 years) from southwest Mexico City (SWMC) (n = 66) and from a control city (n = 93) with criteria pollutant levels below current standards. MC children exhibited significant decreases in the numbers of natural killer cells (p = .003) and increased numbers of mCD14+ monocytes (p < .001) and CD8+ cells (p = .02). Lower concentrations of interferon gamma (p = .009) and granulocyte-macrophage colony-stimulating factor (p < .001), an endotoxin tolerance-like state, systemic inflammation, and an anti-inflammatory response were also present in the highly exposed children. C-reactive protein and the prostaglandin E metabolite levels were positively correlated with twenty-four- and forty-eight-hour cumulative concentrations of PM(2.5). Exposure to urban air pollution is associated with immunodysregulation and systemic inflammation in children and is a major health threat.

Air pollution, cognitive deficits and brain abnormalities: a pilot study with children and dogs.

Exposure to air pollution is associated with neuroinflammation in healthy children and dogs in Mexico City. Comparative studies were carried out in healthy children and young dogs similarly exposed to ambient pollution in Mexico City. Children from Mexico City (n: 55) and a low polluted city (n:18) underwent psychometric testing and brain magnetic resonance imaging MRI. Seven healthy young dogs with similar exposure to Mexico City air pollution had brain MRI, measurement of mRNA abundance of two inflammatory genes cyclooxygenase-2, and interleukin 1 beta in target brain areas, and histopathological evaluation of brain tissue. Children with no known risk factors for neurological or cognitive disorders residing in a polluted urban environment exhibited significant deficits in a combination of fluid and crystallized cognition tasks. Fifty-six percent of Mexico City children tested showed prefrontal white matter hyperintense lesions and similar lesions were observed in dogs (57%). Exposed dogs had frontal lesions with vascular subcortical pathology associated with neuroinflammation, enlarged Virchow-Robin spaces, gliosis, and ultrafine particulate matter deposition. Based on the MRI findings, the prefrontal cortex was a target anatomical region in Mexico City children and its damage could have contributed to their cognitive dysfunction. The present work presents a groundbreaking, interdisciplinary methodology for addressing relationships between environmental pollution, structural brain alterations by MRI, and cognitive deficits/delays in healthy children.

Long-term air pollution exposure is associated with neuroinflammation, an altered innate immune response, disruption of the blood-brain barrier, ultrafine particulate deposition, and accumulation of amyloid beta-42 and alpha-synuclein in children and young adults.

Air pollution is a serious environmental problem. We investigated whether residency in cities with high air pollution is associated with neuroinflammation/neurodegeneration in healthy children and young adults who died suddenly. We measured mRNA cyclooxygenase-2, interleukin-1beta, and CD14 in target brain regions from low (n = 12) or highly exposed residents (n = 35) aged 25.1 +/- 1.5 years. Upregulation of cyclooxygenase-2, interleukin-1beta, and CD14 in olfactory bulb, frontal cortex, substantia nigrae and vagus nerves; disruption of the blood-brain barrier; endothelial activation, oxidative stress, and inflammatory cell trafficking were seen in highly exposed subjects. Amyloid beta42 (Abeta42) immunoreactivity was observed in 58.8% of apolipoprotein E (APOE) 3/3 < 25 y, and 100% of the APOE 4 subjects, whereas alpha-synuclein was seen in 23.5% of < 25 y subjects. Particulate material (PM) was seen in olfactory bulb neurons, and PM < 100 nm were observed in intraluminal erythrocytes from lung, frontal, and trigeminal ganglia capillaries. Exposure to air pollution causes neuroinflammation, an altered brain innate immune response, and accumulation of Abeta42 and alpha-synuclein starting in childhood. Exposure to air pollution should be considered a risk factor for Alzheimer's and Parkinson's diseases, and carriers of the APOE 4 allele could have a higher risk of developing Alzheimer's disease if they reside in a polluted environment.

Elevated plasma endothelin-1 and pulmonary arterial pressure in children exposed to air pollution.

BACKGROUND: Controlled exposures of animals and humans to particulate matter (PM) or ozone air pollution cause an increase in plasma levels of endothelin-1, a potent vasoconstrictor that regulates pulmonary arterial pressure. OBJECTIVES: The primary objective of this field study was to determine whether Mexico City children, who are chronically exposed to levels of PM and O(3) that exceed the United States air quality standards, have elevated plasma endothelin-1 levels and pulmonary arterial pressures. METHODS: We conducted a study of 81 children, 7.9 +/- 1.3 years of age, lifelong residents of either northeast (n = 19) or southwest (n = 40) Mexico City or Polotitlán (n = 22), a control city with PM and O(3) levels below the U.S. air quality standards. Clinical histories, physical examinations, and complete blood counts were done. Plasma endothelin-1 concentrations were determined by immunoassay, and pulmonary arterial pressures were measured by Doppler echocardiography. RESULTS: Mexico City children had higher plasma endothelin-1 concentrations compared with controls (p < 0.001). Mean pulmonary arterial pressure was elevated in children from both northeast (p < 0.001) and southwest (p < 0.05) Mexico City compared with controls. Endothelin-1 levels in Mexico City children were positively correlated with daily outdoor hours (p = 0.012), and 7-day cumulative levels of PM air pollution < 2.5 mum in aerodynamic diameter (PM(2.5)) before endothelin-1 measurement (p = 0.03). CONCLUSIONS: Chronic exposure of children to PM(2.5) is associated with increased levels of circulating endothelin-1 and elevated mean pulmonary arterial pressure.

Pediatric respiratory and systemic effects of chronic air pollution exposure: nose, lung, heart, and brain pathology.

Exposures to particulate matter and gaseous air pollutants have been associated with respiratory tract inflammation, disruption of the nasal respiratory and olfactory barriers, systemic inflammation, production of mediators of inflammation capable of reaching the brain and systemic circulation of particulate matter. Mexico City (MC) residents are exposed to significant amounts of ozone, particulate matter and associated lipopolysaccharides. MC dogs exhibit brain inflammation and an acceleration of Alzheimer's-like pathology, suggesting that the brain is adversely affected by air pollutants. MC children, adolescents and adults have a significant upregulation of cyclooxygenase-2 (COX2) and interleukin-1beta (IL-1beta) in olfactory bulb and frontal cortex, as well as neuronal and astrocytic accumulation of the 42 amino acid form of beta -amyloid peptide (Abeta 42), including diffuse amyloid plaques in frontal cortex. The pathogenesis of Alzheimer's disease (AD) is characterized by brain inflammation and the accumulation of Abeta 42, which precede the appearance of neuritic plaques and neurofibrillary tangles, the pathological hallmarks of AD. Our findings of nasal barrier disruption, systemic inflammation, and the upregulation of COX2 and IL-1beta expression and Abeta 42 accumulation in brain suggests that sustained exposures to significant concentrations of air pollutants such as particulate matter could be a risk factor for AD and other neurodegenerative diseases.

Lung radiology and pulmonary function of children chronically exposed to air pollution.

We analyzed the chest radiographs (CXRs) of 249 clinically healthy children, 230 from southwest Mexico City and 19 from Tlaxcala. In contrast to children from Tlaxcala, children from southwest Mexico City were chronically exposed to ozone levels exceeding the U.S. National Ambient Air Quality Standards for an average of 4.7 hr/day and to concentrations of particulate matter (PM) with aerodynamic diameters