Fatty alcohols, a minor component of the tree tobacco surface wax, are associated with defence against caterpillar herbivory.

Despite decades of research resulting in a comprehensive understanding of epicuticular wax metabolism, the function of these almost ubiquitous metabolites in plant-herbivore interactions remains unresolved. In this study, we examined the effects of CRISPR-induced knockout mutations in four Nicotiana glauca (tree tobacco) wax metabolism genes. These mutations cause a wide range of changes in epicuticular wax composition, leading to altered interactions with insects and snails. Three interaction classes were examined: chewing herbivory by seven caterpillars and one snail species, phloem feeding by Myzus persicae (green peach aphid) and oviposition by Bemisia tabaci (whitefly). Although total wax load and alkane abundance did not affect caterpillar growth, a correlation across species, showed that fatty alcohols, a minor component of N. glauca surface waxes, negatively affected the growth of both a generalist caterpillar (Spodoptera littoralis) and a tobacco-feeding specialist (Manduca sexta). This negative correlation was overshadowed by the stronger effect of anabasine, a nicotine isomer, and was apparent when fatty alcohols were added to an artificial lepidopteran diet. By contrast, snails fed more on waxy leaves. Aphid reproduction and feeding activity were unaffected by wax composition but were potentially affected by altered cutin composition. Wax crystal morphology could explain the preference of B. tabaci to lay eggs on waxy wild-type plants relative to both alkane and fatty alcohol-deficient mutants. Together, our results suggest that the varied responses among herbivore classes and species are likely to be a consequence of the co-evolution that shaped the specific effects of different surface wax components in plant-herbivore interactions.

Intoxicaciones por benzodiacepinas y antidepresivos, una realidad preocupante / Epidemiological Characterization of Benzodiazepine and Antidepressant Poisonings in Chile

INTRODUCTION: Poisonings are a worldwide preventable public health problem that affects the general population. OBJECTIVE: To epidemiologically characterize BZ and AD poisonings registered in Chile between 2002 and 2019. METHODS: An observational retrospective study of poisonings registered in the medical outcome report system of the Chilean Ministry of Health was conducted. The World Health Organization International Classification of Disease codes T42.2, T43.0 and T43.2 were included. RESULTS: 22,807 poisonings associated with BZ or AD were identified, representing 0.08% of all hospitalizations. Poisoning rates distribution were established at regional and national level. There were 9.8% of accidental events, 63.7% of intentional events, and 26.5% of undetermined cases. The highest accidental and intentional poisoning rates were estimated at the ages of 0 to 4 and 15 to 19 years old respectively. Poisoned patients remained hospitalized on average for 3.4 days. 0.3% of cases were related to death of patients. CONCLUSIONS: Poisoning events were characterized according to the studied variables. National poisoning rates decreased over the years with prevalence of those intentional events linked to women. Efforts should be made in creating poisoning prevention campaigns focused on age-based groups in the general population.

Carcinogenic drug exposure among health-sector workers: the need for exposure assessment and surveillance.

Antineoplastic drugs (ANDs) used for chemotherapy can cause secondary cancers in treated patients and can pose carcinogenic risks to health-sector workers anywhere along these drugs' life cycle in a facility, from production to patient administration. Several PAHO/WHO Collaborating Centers (CCs) have experience addressing these hazards in the health sector. The objectives of this report are four-fold: 1) Provide an overview of longstanding research and prevention efforts, led by PAHO/WHO and its Occupational Health CCs, aimed at reducing the burden of occupational cancer in the Americas; 2) Discuss how robust AND exposure assessment and educational/outreach work by PAHO CCs can form the basis of exposure mitigation efforts among health-sector workers; 3) Through the presentation of original AND exposure assessment data from a pharmaceutical compounding facility in Chile, highlight relatively inexpensive methods by which such data can be generated; and 4) Discuss how effective, periodic environmental surveillance in healthcare facilities results in the identification of AND contamination in the work environment and enables the implementation of low-cost, high-impact interventions to reduce the risk of occupational cancer in health-sector workers, including in limited-resource settings. The risk of health-sector worker exposure to ANDs and other hazardous drugs is an important issue for inclusion within PAHO/WHO's broader efforts at reducing the impact of occupational cancer in the Americas. This report demonstrates that a wide range of accessible AND-exposure mitigation strategies are feasible at both a facility and a national policy level across the hemisphere.

Los medicamentos antineoplásicos empleados en quimioterapia pueden causar distintos tipos de tumores secundarios en pacientes tratados y presentar riesgos cancerígenos para los trabajadores del sector de la salud en cualquier momento del ciclo de vida de estos medicamentos en las instalaciones, desde su producción hasta su administración al paciente. Varios centros colaboradores de la OPS/OMS tienen experiencia en cuanto a cómo abordar estos peligros en el sector de la salud. Este informe persigue cuatro objetivos: 1) ofrecer una visión general de la labor de investigación y prevención de larga data, liderada por la OPS/OMS y sus centros colaboradores de salud ocupacional, encaminada a reducir la carga del cáncer ocupacional en la Región de las Américas; 2) abordar cómo una evaluación sólida de la exposición a los medicamentos antineoplásicos y la labor educativa y divulgativa de los centros colaboradores de la OPS pueden sentar las bases de los esfuerzos de mitigación de la exposición en los trabajadores del sector de la salud; 3) mediante la presentación de datos originales sobre la evaluación de la exposición a los medicamentos antineoplásicos en una instalación de compuestos farmacéuticos en Chile, destacar métodos relativamente asequibles gracias a los cuales se pueden recopilar dichos datos; y 4) examinar cómo la vigilancia ambiental efectiva y periódica en los centros de salud permite detectar casos de contaminación de medicamentos antineoplásicos en el entorno de trabajo y facilita la ejecución de intervenciones de bajo costo y alto impacto para reducir el riesgo de cáncer ocupacional en los trabajadores del sector de la salud, incluso en entornos de recursos limitados.El riesgo de exposición de los trabajadores del sector de la salud a los medicamentos antineoplásicos y otros medicamentos peligrosos es una cuestión importante para su inclusión en los esfuerzos más amplios de la OPS/OMS para reducir los efectos del cáncer ocupacional en la Región de las Américas. En este informe se demuestra que una amplia gama de estrategias accesibles de mitigación de la exposición a los medicamentos antineoplásicos es factible tanto a nivel de las instalaciones como de las políticas nacionales en toda la Región.

Os medicamentos antineoplásicos usados para quimioterapia podem causar cânceres secundários em pacientes tratados e apresentar riscos carcinogênicos aos profissionais de saúde em qualquer momento do ciclo de vida desses fármacos dentro de um estabelecimento, desde sua produção até a administração ao paciente. Vários centros colaboradores da OPAS/OMS têm experiência em lidar com esses riscos no setor de saúde. Este relatório tem quatro objetivos: 1) fornecer uma visão geral dos esforços de longa data em pesquisa e prevenção liderados pela OPAS/OMS e por seus centros colaboradores de saúde ocupacional, cuja meta é reduzir a carga do câncer ocupacional nas Américas; 2) discutir como uma avaliação robusta da exposição aos antineoplásicos e o trabalho de extensão/educacional dos centros colaboradores da OPAS/OMS podem embasar os esforços de mitigação da exposição entre os profissionais de saúde; 3) por meio da apresentação de dados originais de avaliação da exposição a antineoplásicos obtidos de uma central de manipulação de medicamentos no Chile, destacar métodos relativamente econômicos para gerar esse tipo de dados; e 4) discutir como a vigilância ambiental eficaz e periódica em estabelecimentos de saúde resulta na identificação de contaminação por antineoplásicos no ambiente de trabalho e permite a implementação de intervenções de baixo custo e alto impacto para reduzir o risco de câncer ocupacional em profissionais de saúde, inclusive em contextos de recursos limitados.O risco de exposição dos profissionais de saúde aos medicamentos antineoplásicos e outros fármacos perigosos é uma questão importante a ser incluída nos esforços mais amplos da OPAS/OMS de reduzir o impacto do câncer ocupacional nas Américas. Este relatório demonstra a viabilidade de uma ampla gama de estratégias acessíveis de mitigação da exposição aos antineoplásicos, tanto no nível das instituições quanto no âmbito de políticas nacionais em todo o hemisfério.

Carcinogenic drug exposure among health-sector workers: the need for exposure assessment and surveillance / Exposición a medicamentos cancerígenos en trabajadores del sector de la salud: necesidad de evaluación y vigilancia de la exposición / Exposição a fármacos carcinogênicos entre profissionais de saúde: necessidade de avaliação e vigilância da exposição

ABSTRACT Antineoplastic drugs (ANDs) used for chemotherapy can cause secondary cancers in treated patients and can pose carcinogenic risks to health-sector workers anywhere along these drugs' life cycle in a facility, from production to patient administration. Several PAHO/WHO Collaborating Centers (CCs) have experience addressing these hazards in the health sector. The objectives of this report are four-fold: 1) Provide an overview of longstanding research and prevention efforts, led by PAHO/WHO and its Occupational Health CCs, aimed at reducing the burden of occupational cancer in the Americas; 2) Discuss how robust AND exposure assessment and educational/outreach work by PAHO CCs can form the basis of exposure mitigation efforts among health-sector workers; 3) Through the presentation of original AND exposure assessment data from a pharmaceutical compounding facility in Chile, highlight relatively inexpensive methods by which such data can be generated; and 4) Discuss how effective, periodic environmental surveillance in healthcare facilities results in the identification of AND contamination in the work environment and enables the implementation of low-cost, high-impact interventions to reduce the risk of occupational cancer in health-sector workers, including in limited-resource settings. The risk of health-sector worker exposure to ANDs and other hazardous drugs is an important issue for inclusion within PAHO/WHO's broader efforts at reducing the impact of occupational cancer in the Americas. This report demonstrates that a wide range of accessible AND-exposure mitigation strategies are feasible at both a facility and a national policy level across the hemisphere.

RESUMEN Los medicamentos antineoplásicos empleados en quimioterapia pueden causar distintos tipos de tumores secundarios en pacientes tratados y presentar riesgos cancerígenos para los trabajadores del sector de la salud en cualquier momento del ciclo de vida de estos medicamentos en las instalaciones, desde su producción hasta su administración al paciente. Varios centros colaboradores de la OPS/OMS tienen experiencia en cuanto a cómo abordar estos peligros en el sector de la salud. Este informe persigue cuatro objetivos: 1) ofrecer una visión general de la labor de investigación y prevención de larga data, liderada por la OPS/OMS y sus centros colaboradores de salud ocupacional, encaminada a reducir la carga del cáncer ocupacional en la Región de las Américas; 2) abordar cómo una evaluación sólida de la exposición a los medicamentos antineoplásicos y la labor educativa y divulgativa de los centros colaboradores de la OPS pueden sentar las bases de los esfuerzos de mitigación de la exposición en los trabajadores del sector de la salud; 3) mediante la presentación de datos originales sobre la evaluación de la exposición a los medicamentos antineoplásicos en una instalación de compuestos farmacéuticos en Chile, destacar métodos relativamente asequibles gracias a los cuales se pueden recopilar dichos datos; y 4) examinar cómo la vigilancia ambiental efectiva y periódica en los centros de salud permite detectar casos de contaminación de medicamentos antineoplásicos en el entorno de trabajo y facilita la ejecución de intervenciones de bajo costo y alto impacto para reducir el riesgo de cáncer ocupacional en los trabajadores del sector de la salud, incluso en entornos de recursos limitados. El riesgo de exposición de los trabajadores del sector de la salud a los medicamentos antineoplásicos y otros medicamentos peligrosos es una cuestión importante para su inclusión en los esfuerzos más amplios de la OPS/OMS para reducir los efectos del cáncer ocupacional en la Región de las Américas. En este informe se demuestra que una amplia gama de estrategias accesibles de mitigación de la exposición a los medicamentos antineoplásicos es factible tanto a nivel de las instalaciones como de las políticas nacionales en toda la Región.

RESUMO Os medicamentos antineoplásicos usados para quimioterapia podem causar cânceres secundários em pacientes tratados e apresentar riscos carcinogênicos aos profissionais de saúde em qualquer momento do ciclo de vida desses fármacos dentro de um estabelecimento, desde sua produção até a administração ao paciente. Vários centros colaboradores da OPAS/OMS têm experiência em lidar com esses riscos no setor de saúde. Este relatório tem quatro objetivos: 1) fornecer uma visão geral dos esforços de longa data em pesquisa e prevenção liderados pela OPAS/OMS e por seus centros colaboradores de saúde ocupacional, cuja meta é reduzir a carga do câncer ocupacional nas Américas; 2) discutir como uma avaliação robusta da exposição aos antineoplásicos e o trabalho de extensão/educacional dos centros colaboradores da OPAS/OMS podem embasar os esforços de mitigação da exposição entre os profissionais de saúde; 3) por meio da apresentação de dados originais de avaliação da exposição a antineoplásicos obtidos de uma central de manipulação de medicamentos no Chile, destacar métodos relativamente econômicos para gerar esse tipo de dados; e 4) discutir como a vigilância ambiental eficaz e periódica em estabelecimentos de saúde resulta na identificação de contaminação por antineoplásicos no ambiente de trabalho e permite a implementação de intervenções de baixo custo e alto impacto para reduzir o risco de câncer ocupacional em profissionais de saúde, inclusive em contextos de recursos limitados. O risco de exposição dos profissionais de saúde aos medicamentos antineoplásicos e outros fármacos perigosos é uma questão importante a ser incluída nos esforços mais amplos da OPAS/OMS de reduzir o impacto do câncer ocupacional nas Américas. Este relatório demonstra a viabilidade de uma ampla gama de estratégias acessíveis de mitigação da exposição aos antineoplásicos, tanto no nível das instituições quanto no âmbito de políticas nacionais em todo o hemisfério.

Estudio retrospectivo de pacientes intoxicados admitidos en la unidad de cuidados intensivos pediátricos de un hospital en Chile / Retrospective study of poisoned patients admitted to a hospital's pediatric intensive care unit in Chile

Introducción. Las intoxicaciones pediátricas son un problema de salud pública a nivel mundial. El objetivo de este estudio fue caracterizar las intoxicaciones pediátricas que fueron atendidas en la unidad de cuidados intensivos pediátricos (UCIP) de un hospital en Chile. Población y métodos. Se revisaron las fichas clínicas de pacientes diagnosticados con intoxicación e ingresados a la UCIP entre los años 2013 y 2017. Resultados. Un total de 105 casos fueron identificados, lo que representa un 3 % del total de ingresos registrados en el período estudiado. La mediana de edad de los pacientes resultó ser de 10 años. El 73,3 % de los casos correspondieron a pacientes de sexo femenino. El 51 % de los casos se asociaron a intoxicaciones intencionales y el 83 % fue causado por exposición a medicamentos. Los medicamentos identificados con mayor frecuencia fueron los antidepresivos (11,2 %), analgésicos no esteroides (10,7 %). La ingesta fue la vía de exposición más común (93 %). El promedio de estadía de los pacientes en UCIP fue de 1,3 días. Dos pacientes ingresaron en la UCI: uno requirió intubación y otro hemodiálisis. Se determinaron relaciones estadísticamente significativas entre el sexo del paciente y la circunstancia de exposición, y entre la condición psiquiátrica del paciente y el número de sustancias tóxicas ingeridas. Conclusión. La mayoría de las intoxicaciones atendidas en la UCIP fueron intencionales y correspondieron a pacientes de sexo femenino, a quienes se les asoció alguna patología psiquiátrica. Los grupos de medicamentos identificados con mayor frecuencia fueron los antidepresivos y los antiinflamatorios no esteroides.

Introduction. Pediatric poisoning is a public health problem worldwide. The objective of this study was to establish the characteristics of pediatric cases of poisoning seen at the pediatric intensive care unit (PICU) of a hospital in Chile. Population and methods. The medical records of patients diagnosed with poisoning and admitted to the PICU between 2013 and 2017 were reviewed. Results. A total of 105 cases were identified, who account for 3% of all admissions recorded in the study period. Patients' median age was 10 years. In total, 73.3% of cases were female patients; 51% of cases were associated with intentional poisoning; and 83% were caused by drug exposure. The most common drugs identified were antidepressants (11.2%) and non-steroidal anti-inflammatory drugs (10.7%). Intake was the most frequent route of exposure (93%). The average length of stay in the PICU was 1.3 days. One patient required intubation and another required hemodialysis in the PICU. Statistically significant relationships were established between patient sex and the circumstance of exposure and between the patient's psychiatric condition and the number of toxic substances ingested. Conclusion. Most poisoning cases seen at the PICU were intentional and occurred in female patients, who had a psychiatric condition. The most common drugs identified were antidepressants and non-steroidal antiinflammatory drugs.

A mutation increases the specificity to plant compounds in an insect chemosensory protein.

Host plant recognition are highly dependent on chemosensory perception, which involves chemosensory proteins (CSPs) that bind key chemical compounds the host plants. In this work, we hypothesize that two closely related aphid taxa, which differ in diet breadth, also differ in their CSPs. We detected a non-synonymous difference (lysine for asparagine) between M. persicae sensu stricto (Mpp) and the subspecies M. p. nicotianae (Mpn) in the sequence of a CSP (CSP5). We modeled in silico the binding capacity of both CSP5s variants with 163 different potential ligands from their host plants (120 unique from tobacco, 29 unique from peach, and 14 common ligands). After docking analysis with all ligands, we selected the three best ligands for each variant to perform molecular dynamics (tobacco: 2-cyclopentene-1,4-dione, salicylaldehyde, and benzoic acid; peach: phenol, valeric acid, and benzonitrile). The binding energy of the MpnCSP5 model to the studied ligands was, in all cases, lower than with the MppCSP5 model. The ligands from the host plants showed more stable binding with MpnCSP5 than with MppCSP5. This result suggests that the set of CSPs studied among M. persicae s. str. and M. p. nicotianae are very similar, but focusing on the CSP5 protein, we found a single key mutation that increases affinities for host compounds for M. p. nicotianae, which might have contributed to the specialization to tobacco. This study provides new insights into an evolutionary trend toward specificity in a binding protein.

Adherencia terapéutica, interacción equipo médico-paciente y justicia social en población indígena Mixteca de Guerrero, México / Therapeutic adeherence, doctor-patient interaction and social justice in Mixteca indigenus population from Guerrero, México / Adesão terapêutica, interação equipe médica-paciente e justiça social em população indígena Mixteca de Guerrero, México

Resumen: En México habitan diversos grupos sociales, entre ellos se encuentra el pueblo indígena de los mixtecos, que en su mayoría se caracteriza por vivir en condiciones de extrema pobreza, situación que posibilita estados desfavorables de salud por las características sociales y físicas particulares. Además, estos grupos indígenas utilizan sistemas médicos propios, distintos al sistema biomédico. Cuando el Gobierno amplía su cobertura a estas comunidades se presentan dificultades debido a la incompatibilidad de sistemas médicos. Se ha observado que el uso de habilidades interculturales, tales como los componentes verbales valorativos y transcriptivos, favorece un ajuste entre los pacientes y los sistemas biomédicos de salud. Con el objetivo de revisar si los profesionales que prestan sus servicios a comunidades indígenas presentan habilidades interculturales, se llevó a cabo un estudio descriptivo, no experimental, y transversal para identificar el uso de componentes verbales interculturales por parte del equipo médico de la Unidad Médica Rural, ubicada en la comunidad de Dos Ríos, municipio de Cochoapa el Grande, Guerrero. Se observó la interacción equipo médico-paciente durante 6 meses, con un total de 103 consultas registradas. Asimismo, se contempló que los profesionales tienen un escaso uso de los componentes verbales interculturales y que no han incorporado estrategias que permitan el ajuste médico de los pacientes mixtecos al sistema biomédico. Los datos se analizan con relación a los aspectos bioéticos y de justicia social implicados en el comportamiento de las instituciones oficiales de salud.

Abstract: Mexico's inhabitants comprise various social groups and among them we find the indigenous people of the Mixtecos, who are mostly characterized by living in extreme poverty conditions, a situation that enables unfavorable health conditions due to their particular social and physical characteristics. Furthermore, these indigenous groups use their own medical systems, different from the biomedical system. When the Government extends its coverage to these communities, difficulties arise due to the incompatibility of medical systems. The use of intercultural skills, such as evaluative and transcriptional verbal components, has been observed to favor an adjustment between patients and biomedical health systems. With the aim of reviewing whether the professionals who provide their services to indigenous communities have intercultural skills, a descriptive, non-experimental, cross-sectional study was carried out to identify the use of intercultural verbal components by the medical team of the Rural Medical Unit, located in the community of Dos Ríos, municipality of Cochoapa el Grande, Guerrero. The doctor-patient team interaction was observed for 6 months, with a total of 103 registered consultations. Likewise, it was found that professionals have little use of intercultural verbal components and that they have not incorporated strategies that allow the medical adjustment of Mixtec patients to the biomedical system. Data was analyzed in relation to the bioethical and social justice aspects involved in the behavior of official health institutions.

Resumo: No México, há diversos grupos sociais, entre eles se encontra o povo indígena dos mixtecos, que, em sua maioria, é caracterizado por viver em condições de extrema pobreza, situação que possibilita estados desfavoráveis de saúde. Além disso, esses grupos indígenas utilizam sistemas médicos próprios, diferentes do sistema biomédico. Quando o governo amplia a cobertura dessas comunidades, são apresentadas dificuldades devido à incompatibilidade de sistemas médicos. Observa-se que o uso de habilidades interculturais, como os componentes verbais valorativos e transcritivos, favorece uma adaptação entre os pacientes e os sistemas biomédicos de saúde. A fim de revisar se os profissionais que prestam serviços a comunidades indígenas apresentam habilidades interculturais, realizou-se estudo descritivo, não experimental e transversal para identificar o uso de componentes verbais interculturais por parte da equipe médica da Unidade Médica Rural, localizada na comunidade de Dos Ríos, município de Cochoapa el Grande, Guerrero. Observou-se a interação equipe médica-paciente durante seis meses, com um total de 103 consultas registradas. A partir disso, foi verificado que os profissionais têm um escasso uso dos componentes verbais interculturais e que não incorporaram estratégias que permitam a adaptação médica dos pacientes mixtecos ao sistema biomédico. Os dados são analisados quanto aos aspectos bioéticos e de justiça social envolvidos no comportamento das instituições oficiais de saúde.

Use of the Tissue Common Rejection Module Score in Kidney Transplant as an Objective Measure of Allograft Inflammation.

Long-term kidney transplant (KT) allograft outcomes have not improved as expected despite a better understanding of rejection and improved immunosuppression. Previous work had validated a computed rejection score, the tissue common rejection module (tCRM), measured by amplification-based assessment of 11 genes from formalin-fixed paraffin-embedded (FFPE) biopsy specimens, which allows for quantitative, unbiased assessment of immune injury. We applied tCRM in a prospective trial of 124 KT recipients, and contrasted assessment by tCRM and histology reads from 2 independent pathologists on protocol and cause biopsies post-transplant. Four 10-µm shaves from FFPE biopsy specimens were used for RNA extraction and amplification by qPCR of the 11 tCRM genes, from which the tCRM score was calculated. Biopsy diagnoses of either acute rejection (AR) or borderline rejection (BL) were considered to have inflammation present, while stable biopsies had no inflammation. Of the 77 biopsies that were read by both pathologists, a total of 40 mismatches in the diagnosis were present. The median tCRM scores for AR, BL, and stable diagnoses were 4.87, 1.85, and 1.27, respectively, with an overall significant difference among all histologic groups (Kruskal-Wallis, p < 0.0001). There were significant differences in tCRM scores between pathologists both finding inflammation vs. disagreement (p = 0.003), and both finding inflammation vs. both finding no inflammation (p < 0.001), along with overall significance between all scores (Kruskal-Wallis, p < 0.001). A logistic regression model predicting graft inflammation using various clinical predictor variables and tCRM revealed the tCRM score as the only significant predictor of graft inflammation (OR: 1.90, 95% CI: 1.40-2.68, p < 0.0001). Accurate, quantitative, and unbiased assessment of rejection of the clinical sample is critical. Given the discrepant diagnoses between pathologists on the same samples, individuals could utilize the tCRM score as a tiebreaker in unclear situations. We propose that the tCRM quantitative score can provide unbiased quantification of graft inflammation, and its rapid evaluation by PCR on the FFPE shave can become a critical adjunct to help drive clinical decision making and immunosuppression delivery.

El reconocimiento del sistema indígena de salud. Implicaciones de la cobertura de salud gubernamental en México / Recognizing the Indigenous Healthcare System. Implications of Government Healthcare Coverage in Mexico / O reconhecimento do sistema indígena de saúde. Implicações da cobertura de saúde governamental no México

Resumen El presente artículo tiene como objetivo analizar la situación que se presenta en la atención a la salud de los pueblos indígenas de México, considerando aspectos sociales y teóricos, así como las implicaciones a nivel bioético. Los pueblos indígenas tienen los peores indicadores de salud, por lo que el gobierno se ha planteado como meta construir instituciones médicas que brinden servicio a estos grupos sociales. Sin embargo, no se ha considerado que las culturas indígenas tienen sistemas médicos distintos, lo cual probabiliza una baja frecuencia de utilización, abandonos y poca adherencia terapéutica; además, se soslaya la preservación del conocimiento tradicional indígena, específicamente, de su medicina. La falta de reconocimiento de las diferencias en las realidades sociales del equipo de salud respecto de los pacientes indígenas es un problema bioético, ya que los programas gubernamentales no han considerado las diferencias culturales. Aunque la inequidad social favorece la falta de justicia en este ámbito, se propone enfocar los análisis a la interacción lingüística equipo médico-paciente indígena, considerando la importancia de promover un discurso que permita la comprensión del sistema médico del otro, más que uno que muestre valoraciones negativas. Esta posición podría aportar conocimiento y soluciones en Bioética.

Abstract This article aims to analyze the situation of healthcare of indigenous peoples in Mexico, considering social and theoretical aspects and bioethical implications. Indigenous peoples have the worst health indicators, so the government has set the goal of building medical institutions that provide services to these social groups. However, it has not considered that indigenous cultures have different medical systems, which entails low frequency of use, desertion and poor adherence to therapy. In addition, the preservation of indigenous traditional knowledge, specifically their medicine, is ignored. The health team's failure to recognize differences in social realities with respect to indigenous patients is a bioethical problem since government programs have not contemplated cultural diversity. Although social inequality favors injustice in this area, we propose to focus analyses on the medical team-indigenous patient linguistic interaction because of the significance of promoting a discourse to understand the other's medical system, rather than one that reflects negative opinions. This stand could provide knowledge and solutions to bioethics.

Resumo Este artigo tem como objetivo analisar a situação que se apresenta na atenção de saúde dos povos indígenas do México, considerando aspectos sociais e teóricos, bem como as implicações no âmbito bioético. Os povos indígenas têm os piores indicadores de saúde, razão pela qual o governo propôs como meta construir instituições médicas que ofereçam serviço a esses grupos sociais. Contudo, não foi considerado que as culturas indígenas têm sistemas médicos diferentes, o que justificaria uma baixa frequência de sua utilização, abandonos e pouca adesão terapêutica; além disso, ignora-se a preservação do conhecimento tradicional indígena, em específico de sua medicina. A falta de reconhecimento das diferenças nas realidades sociais da equipe de saúde a respeito dos pacientes indígenas é um problema bioético, já que os programas governamentais não consideram as diferenças culturais. Embora a inequidade social favoreça a falta de justiça nesse contexto, propõe-se focar as análises na interação linguística equipe médica-paciente indígena, considerando a importância de promover um discurso que permita a compreensão do sistema médico do outro, mais do que um que mostra avaliações negativas. Essa posição poderia contribuir com conhecimento e soluções em bioética.

Protective Effects of 17ß-Estradiol on Benzo(e) pyrene[B(e)P]-induced Toxicity in ARPE-19 cells.

PURPOSE: The aim of this study was to examine the effect of 17ß-estradiol on Benzo(e)pyrene [B(e)P]-induced toxicity in ARPE-19 cells. METHODS: We pretreated ARPE-19 cells with 20 nM and 40 nM 17ß-estradiol for 6 hours, followed by addition of 300 µM B(e)P for additional 24 hours. Cell viability was measured using Trypan blue dye-exclusion assay. JC-1 assay was performed to measure mitochondrial membrane potential (ΔΨm). For a quantitative estimation of cell death, apoptotic markers such as caspase-3/7, caspase-9, and caspase-12 were measured. RESULTS: Our results demonstrated that when treated with B(e)P, the viability and ΔΨm of ARPE-19 cells declined by 25% and 63%, respectively (P < 0.05). However, pretreating with 17ß-estradiol increased the viability of ARPE-19 cells by 21% (20 nM) and 10% (40 nM) (P < 0.05). Furthermore, the significantly reduced ΔΨm in ßE+B(e)P treated cells ARPE-19 cells was restored by pre-treatment with 17ß-estradiol- ΔΨm was increased by 177% (20 nM) and 158% (40 nM) (P < 0.05). We further observed a significant up-regulation in the activity of Caspases-3/7, -9, and -12 in B(e)P-treated ARPE-19 cells. However, 17ß-estradiol treatment significantly reduced the activity of all apoptotic markers (P < 0.05). CONCLUSION: In conclusion, our results demonstrate that 17ß-estradiol protects ARPE-19 cells against B(e)P-induced toxicity by decreasing apoptosis, preventing cell death, and restoring mitochondrial membrane potential.

Protective Effects of Memantine on Hydroquinone-Treated Human Retinal Pigment Epithelium Cells and Human Retinal Müller Cells.

PURPOSE: Memantine (MEM) acts on the glutamatergic system by blocking N-methyl-d-aspartate (NMDA) glutamate receptors. The role that MEM plays in protecting retinal cells is unknown. Hydroquinone (HQ) is one of the cytotoxic components in cigarette smoke. In the present study, we tested whether pretreatment with MEM could protect against the cytotoxic effects of HQ on human retinal pigment epithelium cells (ARPE-19) and human retinal Müller cells (MIO-M1) in vitro. METHODS: Cells were plated, pretreated for 6 h with 30 µM of MEM, and then exposed for 24 h to 200, 100, 50, and 25 µM of HQ while MEM was still present. Cell viability (CV), reactive oxygen species (ROS), mitochondrial membrane potential (ΔΨm), and lactate dehydrogenase (LDH) release assays were performed. RESULTS: HQ-treated cells showed a dose-dependent decrease in CV and ΔΨm, but an increase in ROS production and LDH levels in both cell lines. MEM pretreatment reversed the CV in 50, 100, and 200 µM doses in ARPE-19 cells and at all HQ concentrations in MIO-M1 cells compared to HQ-treated cultures. ROS production was reversed in all HQ concentrations in both cell lines. ΔΨm was significantly increased after MEM pretreatment only in 50 µM HQ concentration for both cell lines. LDH levels were decreased at 50 and 25 µM HQ in ARPE-19 and MIO-M1 cells, respectively. CONCLUSION: HQ-induced toxicity is concentration dependent in ARPE-19 and MIO-M1 cultures. MEM exerts protective effects against HQ-induced toxicity on human retinal pigment epithelial and Müller cells in vitro.

Measuring extent of surface contamination produced by the handling of antineoplastic drugs in low- to middle-income country oncology health care settings.

Antineoplastic drugs are known to cause detrimental effects to health care workers who are exposed through work tasks. Environmental monitoring studies are an excellent approach to measure the extent of surface contamination produced by the handling of antineoplastic drugs in the workplace and to assess the potential for occupational exposures in oncology health care settings. The main aim of the study was to establish the extent of surface contamination produced by the handling of antineoplastic drugs in a limited-resource oncology health care facility in Colombia by conducting an environmental monitoring study using affordable analytical instrumentation. Contamination with antineoplastic drugs was widespread in the health care facility under evaluation, which could result in health care worker exposure to antineoplastic drugs. A comprehensive review of current safety guidelines and protocols including assessment of adherence in the health care facility should be done.

Brimonidine Can Prevent In Vitro Hydroquinone Damage on Retinal Pigment Epithelium Cells and Retinal Müller Cells.

PURPOSE: Brimonidine is a selective alpha-2 adrenergic agonist used to reduce intraocular pressure and it has been shown to have some neuroprotective effects. Hydroquinone (HQ) is a toxicant present in cigarette smoke, and other sources. In this study, we investigated the cyto-protective effects in vitro of Brimonidine on human retinal pigment epithelium cells (ARPE-19) and human retinal Müller cells (MIO-M1) that had been treated with HQ. METHODS: Cells were pretreated for 6 h with different doses of Brimonidine tartrate 0.1% (1/2×, 1×, 5×, 10×), followed by a 24-h exposure to 100 µM of HQ, while the Brimonidine was still present. Assays were used to measure cell viability, mitochondrial membrane potential (ΔΨm), reactive oxygen species (ROS) production, and lactate dehydrogenase (LDH) release. RESULTS: Brimonidine increased the cell viability at all concentrations studied in both cell lines studied. ΔΨm also improved at all Brimonidine doses in ARPE-19 cells and in the 5× and 10× dosages MIO-M1 cells. The ROS levels decreased at 1×, 5×, and 10× doses of Brimonidine in ARPE-19 but only at 10× on MIO-M1 cells. The 10×-Brimonidine ARPE-19 cells had decreased LDH release, but no LDH changes were observed on MIO-M1 cells. CONCLUSION: HQ-induced toxicity is mediated through mitochondrial damaging, oxidative stress-related and necrosis-related pathways; Brimonidine significantly prevented the mitochondrial damaging and oxidative stress-related effects but had little effect on blocking the necrosis component of HQ-toxicity. Brimonidine protective effects differ between the different retinal cell types and high concentrations of Brimonidine (10×) have minimal damaging effects on human retinal cells.

Human retinal transmitochondrial cybrids with J or H mtDNA haplogroups respond differently to ultraviolet radiation: implications for retinal diseases.

BACKGROUND: It has been recognized that cells do not respond equally to ultraviolet (UV) radiation but it is not clear whether this is due to genetic, biochemical or structural differences of the cells. We have a novel cybrid (cytoplasmic hybrids) model that allows us to analyze the contribution of mitochondrial DNA (mtDNA) to cellular response after exposure to sub-lethal dose of UV. mtDNA can be classified into haplogroups as defined by accumulations of specific single nucleotide polymorphisms (SNPs). Recent studies have shown that J haplogroup is high risk for age-related macular degeneration while the H haplogroup is protective. This study investigates gene expression responses in J cybrids versus H cybrids after exposure to sub-lethal doses of UV-radiation. METHODOLOGY/PRINCIPAL FINDINGS: Cybrids were created by fusing platelets isolated from subjects with either H (n = 3) or J (n = 3) haplogroups with mitochondria-free (Rho0) ARPE-19 cells. The H and J cybrids were cultured for 24 hours, treated with 10 mJ of UV-radiation and cultured for an additional 120 hours. Untreated and treated cybrids were analyzed for growth rates and gene expression profiles. The UV-treated and untreated J cybrids had higher growth rates compared to H cybrids. Before treatment, J cybrids showed lower expression levels for CFH, CD55, IL-33, TGF-A, EFEMP-1, RARA, BCL2L13 and BBC3. At 120 hours after UV-treatment, the J cybrids had decreased CFH, RARA and BBC3 levels but increased CD55, IL-33 and EFEMP-1 compared to UV-treated H cybrids. CONCLUSION/SIGNIFICANCE: In cells with identical nuclei, the cellular response to sub-lethal UV-radiation is mediated in part by the mtDNA haplogroup. This supports the hypothesis that differences in growth rates and expression levels of complement, inflammation and apoptosis genes may result from population-specific, hereditary SNP variations in mtDNA. Therefore, when analyzing UV-induced damage in tissues, the mtDNA haplogroup background may be important to consider.

Safety profiles of anti-VEGF drugs: bevacizumab, ranibizumab, aflibercept and ziv-aflibercept on human retinal pigment epithelium cells in culture.

PURPOSE: To compare the safety profiles of antivascular endothelial growth factor (VEGF) drugs ranibizumab, bevacizumab, aflibercept and ziv-aflibercept on retinal pigment epithelium cells in culture. METHODS: Human retinal pigment epithelium cells (ARPE-19) were exposed for 24 h to four anti-VEGF drugs at 1/2×, 1×, 2× and 10× clinical concentrations. Cell viability and mitochondrial membrane potential assay were performed to evaluate early apoptotic changes and rate of overall cell death. RESULTS: Cell viability decreased at 10× concentrations in bevacizumab (82.38%, p=0.0001), aflibercept (82.68%, p=0.0002) and ziv-aflibercept (77.25%, p<0.0001), but not at lower concentrations. However, no changes were seen in cell viability in ranibizumab-treated cells at all concentrations including 10×. Mitochondrial membrane potential was slightly decreased in 10× ranibizumab-treated cells (89.61%, p=0.0006) and 2× and 10× aflibercept-treated cells (88.76%, 81.46%; p<0.01, respectively). A larger reduction in mitochondrial membrane potential was seen at 1×, 2× and 10× concentrations of bevacizumab (86.53%, 74.38%, 66.67%; p<0.01) and ziv-aflibercept (73.50%, 64.83% and 49.65% p<0.01) suggestive of early apoptosis at lower doses, including the clinical doses. CONCLUSIONS: At clinical doses, neither ranibizumab nor aflibercept produced evidence of mitochondrial toxicity or cell death. However, bevacizumab and ziv-aflibercept showed mild mitochondrial toxicity at clinically relevant doses.

Molecular and bioenergetic differences between cells with African versus European inherited mitochondrial DNA haplogroups: implications for population susceptibility to diseases.

The geographic origins of populations can be identified by their maternally inherited mitochondrial DNA (mtDNA) haplogroups. This study compared human cybrids (cytoplasmic hybrids), which are cell lines with identical nuclei but mitochondria from different individuals with mtDNA from either the H haplogroup or L haplogroup backgrounds. The most common European haplogroup is H while individuals of maternal African origin are of the L haplogroup. Despite lower mtDNA copy numbers, L cybrids had higher expression levels for nine mtDNA-encoded respiratory complex genes, decreased ATP (adenosine triphosphate) turnover rates and lower levels of reactive oxygen species production, parameters which are consistent with more efficient oxidative phosphorylation. Surprisingly, GeneChip arrays showed that the L and H cybrids had major differences in expression of genes of the canonical complement system (5 genes), dermatan/chondroitin sulfate biosynthesis (5 genes) and CCR3 (chemokine, CC motif, receptor 3) signaling (9 genes). Quantitative nuclear gene expression studies confirmed that L cybrids had (a) lower expression levels of complement pathway and innate immunity genes and (b) increased levels of inflammation-related signaling genes, which are critical in human diseases. Our data support the hypothesis that mtDNA haplogroups representing populations from different geographic origins may play a role in differential susceptibilities to diseases.

Hydroquinone induces oxidative and mitochondrial damage to human retinal Müller cells (MIO-M1).

PURPOSE: Smoking is a risk factor in the development of a variety of neuroretinal diseases. Therefore, we have investigated the effects of hydroquinone (HQ), a toxicant that is present in high concentrations in cigarette smoke, on a human retinal Müller cell line (MIO-M1). METHODS: MIO-M1 cells were treated for 24h with four different concentrations of HQ (200µM, 100µM, 50µM, and 25µM). Assays were used to measure cell viability, reactive oxygen/nitrogen species (ROS/RNS), mitochondrial dehydrogenase activity (WST assay), caspase-3/7 activity and lactate dehydrogenase (LDH) levels. Western blot analyses with anti-LC3 and anti-GAPDH antibodies were performed on HQ-treated samples. Some cultures were treated with 4µM rapamycin, to induce autophagy, with and without the autophagy inhibitor 3-methyl-adenine (3MA), and levels of ROS/RNS and LDH were measured. RESULTS: Our findings show that HQ reduced cell viability at four different concentrations tested (200, 100, 50 and 25µM); decreased mitochondrial function at concentrations of 200 and 100µM; increased ROS/RNS activity at all the concentrations tested and increased LDH levels at concentrations of 200, 100 and 50µM. Caspase-3/7 activities were not modified by HQ. However, treatment of these cells with this agent resulted in the appearance of the autophagy associated LC3-II band. Pre-treatment with 3MA reduced the ROS/RNS and LDH levels of the HQ-treated and rapamycin-treated cells. CONCLUSION: Our study suggests that HQ damages the MIO-M1 cells through oxidative, mitochondrial and autophagic pathways and not caspase-related apoptosis.

Long-term results of surgical treatment of aneurysms of digestive arteries.

BACKGROUND: The aim of this study was to document the long-term results of open surgical treatment of aneurysms of the digestive arteries. METHODS: Between January 2000 and March 2010, 60 patients were operated on for 78 aneurysms of the digestive arteries at our institution. The mean age of patients was 61 years (31-84 years). The average lesion diameter was 33 mm (range 10-90 mm). Topographic distribution involved the coeliac trunk in 23 cases (30%), hepatic artery in 20 (26%), splenic artery in 19 (24%), superior mesenteric artery in 11 (14%), gastroduodenal artery in 3 (4%), and pancreaticoduodenal arteries in 2 (3%). Twenty patients (33%) were symptomatic, 1 of whom presented with aneurysmal rupture (1.7%). Follow-up was prospective and an actuarial analysis was carried out. Only 3 patients (5%) were lost to follow-up. RESULTS: Hospital mortality was 1.7% (upper gastrointestinal bleeding from gastric metastases of a kidney cancer). Postoperative complications were mainly respiratory (18%), digestive (18%), and renal (13%). Five reintervention procedures (8%) were necessary: 2 for colonic ischemia; 1 for intestinal bleeding; 1 for secondary graft infection due to peritonitis; and 1 for drainage of an acute pancreatitis. The average follow-up was 42 months (range 1-120 months). The actuarial survival rates were 98% at 1 month and 1 year, and 97% at 5 and 10 years, respectively. One late death occurred at 22 months (bronchopulmonary cancer). Three late reinterventions were carried out: 2 re-establishments of digestive continuity and 1 embolization for a recurrent aneurysm 7 years after the initial operation. The primary patency rate of the revascularizations was 98% at 1 month and 1 year, and 95% at 5 and 10 years. The rates of indemnity of restenosis or thrombosis were 98% at 1 month and 1 year, and 95% and 93% to 5 and 10 years, respectively. The rates of freedom of reintervention on bypasses were 98% at 1 month and 1 and 5 years, and 97% at 10 years. CONCLUSION: Open surgical treatment of aneurysms of the digestive arteries offers excellent long-term results in terms of patency. It is with these late results that endovascular techniques will have to be compared to define the best therapeutic strategy.

Mitochondrial DNA variants mediate energy production and expression levels for CFH, C3 and EFEMP1 genes: implications for age-related macular degeneration.

BACKGROUND: Mitochondrial dysfunction is associated with the development and progression of age-related macular degeneration (AMD). Recent studies using populations from the United States and Australia have demonstrated that AMD is associated with mitochondrial (mt) DNA haplogroups (as defined by combinations of mtDNA polymorphisms) that represent Northern European Caucasians. The aim of this study was to use the cytoplasmic hybrid (cybrid) model to investigate the molecular and biological functional consequences that occur when comparing the mtDNA H haplogroup (protective for AMD) versus J haplogroup (high risk for AMD). METHODOLOGY/PRINCIPAL FINDINGS: Cybrids were created by introducing mitochondria from individuals with either H or J haplogroups into a human retinal epithelial cell line (ARPE-19) that was devoid of mitochondrial DNA (Rho0). In cybrid lines, all of the cells carry the same nuclear genes but vary in mtDNA content. The J cybrids had significantly lower levels of ATP and reactive oxygen/nitrogen species production, but increased lactate levels and rates of growth. Q-PCR analyses showed J cybrids had decreased expressions for CFH, C3, and EFEMP1 genes, high risk genes for AMD, and higher expression for MYO7A, a gene associated with retinal degeneration in Usher type IB syndrome. The H and J cybrids also have comparatively altered expression of nuclear genes involved in pathways for cell signaling, inflammation, and metabolism. CONCLUSION/SIGNIFICANCE: Our findings demonstrate that mtDNA haplogroup variants mediate not only energy production and cell growth, but also cell signaling for major molecular pathways. These data support the hypothesis that mtDNA variants play important roles in numerous cellular functions and disease processes, including AMD.

Open repair of vertebral artery: a 7-year single-center report.

BACKGROUND: To report the long-term results of proximal and distal VA open repairs. METHODS: From January 2002 to December 2009, 74 cases of VA open repair were performed (73 patients, 41 men; mean age, 66.5 ± 15.2 years). Symptoms of vertebrobasilar insufficiency were present in 61 cases (82.4%). Forty-seven have had a proximal VA repair, and 27, a distal one. Bypass grafting using a saphenous vein graft was performed in 21 cases (28.3%). Direct transposition was used in 48 (64.8%), mostly into the common carotid artery. RESULTS: Mean duration of follow-up was 39.5 ± 31.3 months. A stroke was present in three patients (4.1%), two hemispheric (2.7%) and one vertebrobasilar (1.3%), which turned lethal. The two hemispheric strokes occurred in the subgroup of 35 procedures combined with a carotid artery reconstruction. A transient Horner syndrome was found in 16 cases (21.6%), and a transient vocal palsy, in six (8.1%). Early postoperative occlusion occurred in two cases (2.7%). A total of seven (9.4%) patients died during follow-up, one from a stroke. Cumulative Kaplan-Meier survival rate was 90.7 ± 4.8% at 3 years and 77.3 ± 12.2% at 6 years. Assessment of late patency was obtained in 54 (84.3%) of 64 survivals by duplex scanning (70.3%) or angiography (10.9%). Significant vertebrobasilar symptom-free rate was 87.7 ± 9.2% at 6 years. Primary patency rate was 94.8 ± 3.8% at 3 years and 90.8 ± 9.4% at 6 years. CONCLUSIONS: VA open repair provides excellent long-term results. Patients with combined carotid and VA reconstruction are at higher risk of postoperative stroke than patients undergoing isolated repair of the VA.