As "Ómicas" como ferramenta no estudo da Saúde Ambiental

Deaths caused by environmental pollution are agrowing public health issue. Most of the premature deaths related to pollution are caused by non communicable diseases such as chronic obstructive pulmonary disease, type-2 diabetes, cardiovascular disease and cancer. They are considered complex diseases because of their multicausality and the various mechanisms involved in their emergence and evolution.Knowledge of disease-causing mechanismsis increasing and the identification of disease-associated biomarkers improving thanks to technological progress, in particular that of the technologiesthat are applied to the measurement and interpretation of molecular components—the so-called “Omics” technologies. These technologies have allowed the cellular causes of some complex diseases to be identified: genetic variants of susceptibility or protection to pollutants (Genomics), as well as changes in the DNA (Epigenomics) and their effects on the process of transcription of specific genes for repair, on metabolism or on the non-coding RNA associated with diseases (Transcriptomics). In addition, Proteomics and Metabolomics do not cease to provide information on proteins and metabolites involved in disease processes. Bioinformatics has evolved parallel to the development of omics, which has allowed the results of the measurements of hundreds of molecules to be interpreted and organized into networks that show the relationships among them.Omics are mainly used to develop disease risk models based on population studies, but information on genomes, transcriptomes, epigenomes, microbiomes, proteomes and metabolomesis also used to decipher diseases in order to facilitate prognosis and guide patient treatment, thus contributing to personalized, precision medicine. However, their clinical application is still limited by their cost and their technical, regulatory and ethical implications.Las muertes provocadas por la contaminación ambiental son un problema de salud pública en incremento. La mayoría de las muertes prematuras provocadas por la contaminación son enfermedades no transmisibles, como enfermedad pulmonar obstructiva crónica, diabetes tipo 2, enfermedades cardiovasculares y cáncer. Estas son consideradas enfermedades complejas por su multicausalidad y los diversos mecanismos involucrados en su aparición y evolución. El conocimiento del mecanismo de producción de la enfermedad, y la identificación de biomarcadores asociados a enfermedad está avanzando gracias al avance de la tecnología, y específicamente de la tecnología aplicada a medición e interpretación de componentes moleculares: las tecnologías “ÓMICAS”. Estas han permitido identificar causas celulares de algunas enfermedades complejas: variantes genéticas de susceptibilidad o protección a agentes contaminantes (Genómica), así como cambios sobre el ADN (Epigenómica) y sus efectos en el proceso de transcripción de genes específicos de reparación, metabolismo o bien RNA no codificante asociado a enfermedades (Transcriptómica); además la Proteómica y la Metabolómica aportan constante información sobre las proteínas y metabolitos involucrados en los procesos de enfermedad. Paralelo al desarrollo de las tecnologías ómicas ha evolucionado la bioinformática, que ha permitido la interpretación de los resultados de mediciones de cientos de moléculas para organizarlos en redes que traducen las relaciones entre ellas. Las tecnologías ómicas se aplican principalmente para determinar modelos de riesgo de enfermedad en base a estudios poblacionales, pero también la información del genoma, transcriptoma, el epigenoma, el microbioma, el proteoma y el metaboloma se utilizarán para ayudar a descifrar la enfermedad a fin de facilitar el pronóstico y guiar el tratamiento de pacientes, ayudando a la medicina individualizada y medicina de precisión. Sin embargo, su aplicación clínica está aún limitada por el costo y las implicaciones técnicas, regulatorias y éticas.As mortes causadas pela poluição ambiental sãoum problema de saúde pública crescente. A maioria das mortes prematuras causadas por contaminação sãodoençasnãotransmissíveis, como doença pulmonar obstrutiva crónica, diabetes tipo 2, doenças cardiovasculares e cancro. Estas são consideradas doenças complexas pela sua multicausalidade e pelos vários mecanismos envolvidos no seu aparecimento e evolução. O conhecimento do mecanismo de produção da doença e a identificação de biomarcadores associados à doençaestá a avançar graçasao desenvolvimento da tecnologia e, especificamente, à tecnologia aplicada à medição e interpretação de componentes moleculares: as tecnologias “ÓMICAS”. Estas permitiram identificar as causas celulares de algumasdoenças complexas: variantes genéticas de suscetibilidade ouproteção a agentes contaminantes (Genómica), bem como alterações no DNA (Epigenética) e os seusefeitos no processo de transcrição de genes específicos de reparação, metabolismo ou RNAnão-codificanteassociado a doenças (Transcriptómica);acresce a Proteómica e a Metabolómica que fornecem informação sobre as proteínas e metabólitosenvolvidos nos processos de doença. Paralelamente ao desenvolvimento das novas técnicas biotecnológicas, geralmente denominadas por “Ómicas”, evoluiu a bioinformática, o que permitiu a interpretação dos resultados das análises de centenas de moléculas para organizá-las em redes que traduzem as relações entre elas. As tecnologias “Ómicas” aplicam-se principalmente para determinar modelos de risco de doença com base em estudos populacionais, mas igualmente a informação do genoma, do transcriptoma, do epigenoma, do microbioma, do proteoma e do metaboloma será usada para ajudar a decifrar a doença, a fim de facilitar o prognóstico e orientar o tratamento dos pacientes, auxiliado a medicina individualizada e a medicina de precisão. No entanto, a sua aplicação clínica ainda é limitada pelo custo e implicações técnicas, regulamentares e éticas

Omics as Environmental Health study tools

Deaths caused by environmental pollution are agrowing public health issue. Most of the premature deaths related to pollution are caused by non communicable diseases such as chronic obstructive pulmonary disease, type-2 diabetes, cardiovascular disease and cancer. They are considered complex diseases because of their multicausality and the various mechanisms involved in their emergence and evolution.Knowledge of disease-causing mechanismsis increasing and the identification of disease-associated biomarkers improving thanks to technological progress, in particular that of the technologiesthat are applied to the measurement and interpretation of molecular components—the so-called “Omics” technologies. These technologies have allowed the cellular causes of some complex diseases to be identified: genetic variants of susceptibility or protection to pollutants (Genomics), as well as changes in the DNA (Epigenomics) and their effects on the process of transcription of specific genes for repair, on metabolism or on the non-coding RNA associated with diseases (Transcriptomics). In addition, Proteomics and Metabolomics do not cease to provide information on proteins and metabolites involved in disease processes. Bioinformatics has evolved parallel to the development of omics, which has allowed the results of the measurements of hundreds of molecules to be interpreted and organized into networks that show the relationships among them.Omics are mainly used to develop disease risk models based on population studies, but information on genomes, transcriptomes, epigenomes, microbiomes, proteomes and metabolomesis also used to decipher diseases in order to facilitate prognosis and guide patient treatment, thus contributing to personalized, precision medicine. However, their clinical application is still limited by their cost and their technical, regulatory and ethical implications.</p

Adhesion, proliferation, and apoptosis in different molecular portraits of breast cancer treated with silver nanoparticles and its pathway-network analysis

Christian M Rodr&iacute;guez-Raz&oacute;n,1 Irinea Ya&ntilde;ez-S&aacute;nchez,2 Vicente O Ramos-Santillan,1 Celso Vel&aacute;squez-Ord&oacute;&ntilde;ez,2 Susan A Guti&eacute;rrez-Rubio,1 Maritza R Garc&iacute;a-Garc&iacute;a,3 Roci&oacute; I L&oacute;pez-Roa,1 Pedro E S&aacute;nchez-Hern&aacute;ndez,1 Adrian Daneri-Navarro,1 Trinidad Garc&iacute;a-Iglesias1 1Laboratory of Immunology and Institute of Experimental and Clinical Therapeutics, Department of Physiology, University Center of Health Sciences, University of Guadalajara, Jalisco, Mexico; 2Center for Research in Nanosciences and Nanotechnology, Department of Natural and Exact Sciences, University Center of the Valleys, University of Guadalajara, Jalisco, Mexico; 3Department of Health Sciences, University Center of the High University of Guadalajara, Jalisco, Mexico Background: Silver nanoparticles (AgNPs) have attracted considerable attention due to the variety of their applications in medicine and other sciences. AgNPs have been used in vitro for treatment of various diseases, such as hepatitis B and herpes simplex infections as well as colon, cervical, and lung cancers. In this study, we assessed the effect on proliferation, adhesion, and apoptosis in breast cancer cell lines of different molecular profiles (MCF7, HCC1954, and HCC70) exposed to AgNPs (2&ndash;9 nm).Methods: Breast cancer cell lines were incubated in vitro; MTT assay was used to assess proliferation. Adhesion was determined by real-time analysis with the xCELLingence system. Propidium iodide and fluorescein isothiocyanate-Annexin V assay were used to measure apoptosis. The transcriptome was assessed by gene expression microarray and Probabilistic Graphical Model (PGM) analyses.Results: The results showed a decreased adhesion in breast cancer cell lines and the control exposed to AgNPs was noted in 24 hours (p&le;0.05). We observed a significant reduction in the proliferation of MCF7 and HCC70, but not in HCC1954. Apoptotic activity was seen in all cell lines exposed to AgNPs, with an apoptosis percentage of more than 60% in cancer cell lines and less than 60% in the control. PGM analysis confirmed, to some extent, the effects of AgNPs primarily on adhesion by changes in the extracellular matrix.Conclusion: Exposure to AgNPs causes an antiproliferative, apoptotic, and anti-adhesive effect in breast cancer cell lines cultured in vitro. More research is needed to evaluate the potential use of AgNPs to treat different molecular profiles of breast cancer in humans. Keywords: silver nanoparticles, breast cancer, adhesion, apoptosis, transcriptom

Tectonic Processes Along the Chile Convergent Margin

The Chile subduction zone, spanning more than 3500 km, provides a unique setting for studying, along a single plate boundary, the factors that govern tectonic processes at convergent margins. At large scale, the Chile trench is segmented by the subduction of the Chile Rise, an active spreading center, and by the Juan Fernández hot spot ridge. In addition, the extreme climatic change from the Atacama Desert in the north to the glacially influenced southern latitudes produces a dramatic variability in the volume of sediment supplied to the trench. The distribution of sediment along the trench is further influenced by the high relief gradients of the segmented oceanic lithosphere. We interpret new and reprocessed multichannel seismic reflection profiles, and multibeam bathymetric data, to study the variability in tectonic processes along the entire convergent margin. In central and south Chile, where the trench contains thick turbidite infill, accretionary prisms, some 50–60 km wide, have developed. These prisms, however, are ephemeral and can be rapidly removed by high-relief, morphological features on the incoming oceanic plate. Where topographic barriers inhibit the transport of turbidites along the trench, sediment infill abruptly decreases to less than 1 km thick and is confined to a narrow zone at the trench axis. There, all sediment is subducted; the margin is extending by normal faulting and collapsing due to basal tectonic erosion. The transition from accretion to tectonic erosion occurs over short distances (a few tens of km) along the trench. In the turbidite-starved northern Chile trench, ~1 km of slope debris reaches the trench and is subsequently subducted. There, tectonic erosion is causing pronounced steepening of the margin, associated pervasive extension across the slope and into the emerged coastal area, and consequent collapse of the overriding plate. The volume of subducting material varies little along much of the margin. However, the composition of the material varies from slope debris of upper-plate fragments and material removed from the upper plate by basal erosion, to turbidites derived from the Andes

Guidelines for the preventive treatment of ischaemic stroke and TIA (I). Update on risk factors and life style

Objective: To update the ad hoc Committee of the Cerebrovascular Diseases Study Group of The Spanish Neurological Society guidelines on prevention of ischaemic stroke (IS) and transient ischaemic attack (TIA). Methods: We reviewed available evidence on risk factors and means of modifying them to prevent IS and TIA. Levels of evidence and recommendation grades are based on the classification of the Centre for Evidence-Based Medicine. Results: This first section summarises the recommendations for action on the following factors: blood pressure, diabetes, lipids, tobacco and alcohol consumption, diet and physical activity, cardio-embolic diseases, asymptomatic carotid stenosis, hormone replacement therapy (HRT) and contraceptives, hyperhomocysteinemia, prothrombotic states and sleep apnea syndrome. Conclusions: Changes in lifestyle and pharmacological treatment for hypertension, diabetes mellitus and dyslipidemia, according to criteria of primary and secondary prevention, are recommended for preventing IS. Resumen: Objetivo: Actualizar las guías terapéuticas del Comité ad hoc del Grupo de Estudio de Enfermedades Cerebrovasculares de la SEN en el tratamiento preventivo de ictus isquémico (II) y ataque isquémico transitorio (AIT). Métodos: Revisión de evidencias disponibles sobre los factores de riesgo y la oportunidad de su modificación para prevenir el ictus isquémico y AIT. Los niveles de evidencia y grados de recomendación se han basado en la clasificación del Centro de Medicina Basada en la Evidencia. Resultados: En esta primera parte se resumen las recomendaciones sobre la actuación sobre los siguientes factores: presión arterial, DM, lípidos plasmáticos, consumo de tabaco y alcohol, dieta y actividad física, cardiopatías embolígenas, estenosis carotídea asintomática, terapia hormonal sustitutiva y anticonceptivos, hiperhomocisteinemía, estados protrombóticos y síndrome de apnea del sueño. Conclusiones: La modificación de los estilos de vida y el tratamiento farmacológico de la hipertensión arterial, diabetes méllitus y dislipemia según criterios de prevención primaria y secundaria se recomiendan en la prevención de ictus isquémico. Keywords: Guidelines, Ischaemic stroke, Transient ischaemic attack, Prevention, Palabras clave: Guías de práctica clínica, Prevención de ictus, Ictus, Ataque isquémico transitori

Guía para el tratamiento preventivo del ictus isquémico y AIT (II). Recomendaciones según subtipo etiológico

Resumen: Fundamento y objetivo: Actualizar las guías terapéuticas del Comité ad hoc del Grupo de Estudio de Enfermedades Cerebrovasculares de la SEN en el tratamiento preventivo de ictus isquémico (II) y ataque isquémico transitorio (AIT). Métodos: Revisión de evidencias disponibles sobre la prevención del ictus isquémico y AIT en función del subtipo etiológico. Los niveles de evidencia y grados de recomendación se han basado en la clasificación del Centro de Medicina Basada en la Evidencia. Resultados: En el II de origen aterotrombótico reducen el riesgo de recurrencias el tratamiento antiagregante y los procedimientos revascularizadores en casos seleccionados de estenosis carotidea ipsilateral (70-99%). La prevención de II de origen cardioembólico (fibrilación auricular, valvulopatías, prótesis valvulares y en infarto de miocardio con trombo mural) se basa en el uso de anticoagulantes orales. En el II de origen inhabitual, las terapias preventivas dependerán de la etiología; en la trombosis venosa cerebral la anticoagulación oral es eficaz. Conclusiones: Se concluye con recomendaciones de práctica clínica en prevención de ictus isquémico y AIT adaptadas al subtipo etiológico de II que ha presentado el paciente. Abstract: Background and Objective: To update the ad hoc Committee of the Cerebrovascular Diseases Study Group of The Spanish Neurological Society guidelines on prevention of ischaemic stroke (IS) and Transient Ischaemic Attack (TIA). Methods: We reviewed the available evidence on ischaemic stroke and TIA prevention according to aetiological subtype. Levels of evidence and recommendation levels are based on the classification of the Centre for Evidence-Based Medicine. Results: In atherothrombotic IS, antiplatelet therapy and revascularization procedures in selected cases of ipsilateral carotid stenosis (70%-90%) reduce the risk of recurrences. In cardioembolic IS (atrial fibrillation, valvular diseases, prosthetic valves and myocardial infarction with mural thrombus) prevention is based on the use of oral anticoagulants. Preventive therapies for uncommon causes of IS will depend on the aetiology. In the case of cerebral venous thrombosis oral anticoagulation is effective. Conclusions: We conclude with recommendations for clinical practice in prevention of IS according to the aetiological subtype presented by the patient. Palabras clave: Guía de práctica clínica, Ictus isquémico, Ataque isquémico transitorio, Prevención, Keywords: Guidelines, Ischaemic stroke, Transient ischemic attack, Preventio

Guidelines for the preventive treatment of ischaemic stroke and TIA (II). Recommendations according to aetiological sub-type

Background and objective: To update the ad hoc Committee of the Cerebrovascular Diseases Study Group of The Spanish Neurological Society guidelines on prevention of ischemic stroke (IS) and Transient Ischaemic Attack (TIA). Methods: We reviewed the available evidence on ischaemic stroke and TIA prevention according to aetiological subtype. Levels of evidence and recommendation levels are based on the classification of the Centre for Evidence-Based Medicine. Results: In atherothrombotic IS, antiplatelet therapy and revascularization procedures in selected cases of ipsilateral carotid stenosis (70–99%) reduce the risk of recurrences. In cardioembolic IS (atrial fibrillation, valvular diseases, prosthetic valves and myocardial infarction with mural thrombus) prevention is based on the use of oral anticoagulants. Preventive therapies for uncommon causes of IS will depend on the aetiology. In the case of cerebral venous thrombosis oral anticoagulation is effective. Conclusions: We conclude with recommendations for clinical practice in prevention of IS according to the aetiological subtype presented by the patient. Resumen: Fundamento y objetivo: Actualizar las guías terapéuticas del Comité ad hoc del Grupo de Estudio de Enfermedades Cerebrovasculares de la SEN en el tratamiento preventivo de ictus isquémico (II) y ataque isquémico transitorio (AIT). Métodos: Revisión de evidencias disponibles sobre la prevención del ictus isquémico y AIT en función del subtipo etiológico. Los niveles de evidencia y grados de recomendación se han basado en la clasificación del Centro de Medicina Basada en la Evidencia. Resultados: En el II de origen aterotrombótico reducen el riesgo de recurrencias el tratamiento antiagregante y los procedimientos revascularizadores en casos seleccionados de estenosis carotidea ipsilateral (70-99%). La prevención de II de origen cardioembólico (fibrilación auricular, valulopatías, prótesis valvulares y en infarto de miocardio con trombo mural) se basa en el uso de anticoagulantes orales. En el II de origen inhabitual, las terapias preventivas dependerán dela etiología; en la trombosis venosa cerebral la anticoagulación oral es eficaz. Conclusiones: Se concluye con recomendaciones de práctica clínica en prevención de ictus isquémico y AIT adaptadas al subtipo etiológico de II que ha presentado el paciente. Keywords: Guidelines, Ischaemic stroke, Transient ischemic attack, Prevention, Palabras clave: Guía de práctica clínica, Ictus isquémico, Ataque isquémico transitorio, Prevenció

Guidelines for the treatment of acute ischaemic stroke

Introduction: Update of Acute Ischaemic Stroke Treatment Guidelines of the Spanish Neurological Society based on a critical review of the literature. Recommendations are made based on levels of evidence from published data and studies. Development: Organised systems of care should be implemented to ensure access to the optimal management of all acute stroke patients in stroke units. Standard of care should include treatment of blood pressure (should only be treated if values are over 185/105 mmHg), treatment of hyperglycaemia over 155 mg/dl, and treatment of body temperature with antipyretic drugs if it rises above 37.5 °C. Neurological and systemic complications must be prevented and promptly treated. Decompressive hemicraniectomy should be considered in cases of malignant cerebral oedema. Intravenous thrombolysis with rtPA should be administered within 4.5 hours from symptom onset, except when there are contraindications. Intra-arterial pharmacological thrombolysis can be considered within 6 hours, and mechanical thrombectomy within 8 hours from onset, for anterior circulation strokes, while a wider window of opportunity up to 12–24 hours is feasible for posterior strokes. There is not enough evidence to recommend routine use of the so-called neuroprotective drugs. Anticoagulation should be administered to patients with cerebral vein thrombosis. Rehabilitation should be started as early as possible. Conclusion: Treatment of acute ischaemic stroke includes management of patients in stroke units. Systemic thrombolysis should be considered within 4.5 hours from symptom onset. Intra-arterial approaches with a wider window of opportunity can be an option in certain cases. Protective and restorative therapies are being investigated. Resumen: Introducción: Actualización de la guía para el tratamiento del infarto cerebral agudo de la Sociedad Española de Neurología basada en la revisión y análisis de la bibliografía existente sobre el tema. Se establecen recomendaciones en base al nivel de evidencia que ofrecen los estudios revisados. Desarrollo: Los sistemas de asistencia urgente extrahospitalaria se organizarán para asegurar la atención especializada de los pacientes y el ingreso en unidades de ictus (UI). Deben aplicarse cuidados generales para mantener la homeostasis (tratar la tensión arterial sistólica > 185 mmHg o diastólica > 105 mmHg, evitar hiperglucemia > 155 mg/dl y controlar la temperatura, tratando con antitérmicos cifras > 37,5 °C), y prevenir y tratar las complicaciones. La craniectomía descompresiva debe ser considerada en casos seleccionados de oedema cerebral maligno. La trombólisis intravenosa con rtPA se administrará en las primeras 4,5 horas en pacientes sin contraindicación. La trombólisis intraarterial farmacológica puede indicarse en las primeras 6 horas de evolución y la trombectomía mecánica hasta las 8 horas. En el territorio posterior la ventana puede ampliarse hasta 12–24 horas. No hay evidencias para recomendar el uso rutinario de los fármacos denominados neuroprotectores. Se recomienda la anticoagulación en pacientes con trombosis de senos venosos. Se aconseja el inicio precoz de rehabilitación. Conclusiones: El tratamiento del infarto cerebral se basa en la atención especializada en UI, la aplicación urgente de cuidados generales y el tratamiento trombolítico intravenoso en las primeras 4,5 horas. La recanalización intraarterial farmacológica o mecánica pueden ser útiles en casos seleccionados. Terapias de protección y reparación cerebral están en desarrollo. Keywords: Cerebral infarct, Ischaemic stroke, Thrombolysis, Brain protection, Stroke units, Cerebral venous thrombosis, Palabras clave: Infarto cerebral, Ictus isquémico, Trombólisis, Cerebroprotección, Unidades de ictus, Trombosis venosa cerebra