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Mimosa tenuiflora (Fabaceae) is popularly known in Brazil as "Jurema preta". From the bark of its root, "jurema wine" is obtained, a psychedelic drink used in Indigenous religious rituals in Northeastern Brazil. This work aimed to investigate the chemical composition and acute oral toxicity of the ethanolic extract of the root bark from M. tenuiflora (EEMt). EEMt was analyzed by UPLC-QToF-MS/MS and DI-ESI-IT-MSn. Oral administration of EEMt was performed once at doses of 300 and 2000 mg/kg in female Swiss mice. Signs and symptoms of intoxication, as well as mortality were monitored for 14 days. Thirteen compounds were annotated in EEMt: eight type B proanthocyanidins, three alkaloids, a glycosylated flavonol, and a dihydrochalcone derivative. The acute administration of 300 and 2000 mg/kg of EEMt did not show mortality. It also did not change the food intake or body weight of the animals. However, the relative weights of the kidneys were significantly changed for both doses. Changes in hematological and biochemical parameters were found. In addition, histopathological changes were also observed in the heart, liver, and kidneys. Thus, based on our findings, EEMt presented an LD50 greater than 2000 mg/kg and was therefore classified in category 5 of the Globally Harmonized Classification System (GHS). EEMt showed acute oral toxicity by altering hematological, biochemical and histological parameters.
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Mimosa , Corteza de la Planta , Extractos Vegetales , Raíces de Plantas , Animales , Extractos Vegetales/toxicidad , Extractos Vegetales/química , Ratones , Femenino , Corteza de la Planta/química , Raíces de Plantas/química , Mimosa/química , Brasil , Pruebas de Toxicidad Aguda , Espectrometría de Masas en Tándem , Metabolómica , Etanol/químicaRESUMEN
Notwithstanding the wide adoption of the OECD principles (or best practices) for QSAR modeling, disparities between in silico predictions and experimental results are frequent, suggesting that model predictions are often too optimistic. Of these OECD principles, the applicability domain (AD) estimation has been recognized in several reports in the literature to be one of the most challenging, implying that the actual reliability measures of model predictions are often unreliable. Applying tree-based error analysis workflows on 5 QSAR models reported in the literature and available in the QsarDB repository, i.e., androgen receptor bioactivity (agonists, antagonists, and binders, respectively) and membrane permeability (highest membrane permeability and the intrinsic permeability), we demonstrate that predictions erroneously tagged as reliable (AD prediction errors) overwhelmingly correspond to instances in subspaces (cohorts) with the highest prediction error rates, highlighting the inhomogeneity of the AD space. In this sense, we call for more stringent AD analysis guidelines which require the incorporation of model error analysis schemes, to provide critical insight on the reliability of underlying AD algorithms. Additionally, any selected AD method should be rigorously validated to demonstrate its suitability for the model space over which it is applied. These steps will ultimately contribute to more accurate estimations of the reliability of model predictions. Finally, error analysis may also be useful in "rational" model refinement in that data expansion efforts and model retraining are focused on cohorts with the highest error rates.
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Algoritmos , Relación Estructura-Actividad Cuantitativa , Reproducibilidad de los ResultadosRESUMEN
This study investigates the dynamic associations among carbon dioxide (CO2) emissions, non-renewable energy production from petroleum derivatives, financial development, and healthcare expenditures to improve environmental quality. This research has employed the balanced annual panel of thirty (30) Organizations for Economic Co-operation and Development (OECD) countries' data set and applied panel vector autoregression (VAR) method depending on the generalized method of moments (GMM). Furthermore, the empirical findings reveal that health spending and CO2 emissions have a favorable bidirectional link, but there is no indication that health spending promotes power generation. The results demonstrate that increased energy consumption and productions affect pollution, and higher CO2 emissions increase healthcare costs. Whereas, energy consumption, financial development, and healthcare expenditures have a positive toward environmental quality.
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Dióxido de Carbono , Gastos en Salud , Dióxido de Carbono/análisis , Desarrollo Económico , Contaminación Ambiental , Producto Interno BrutoRESUMEN
BACKGROUND: Antioxidants are chemicals used to protect foods from deterioration by neutralizing free radicals and inhibiting the oxidative process. One approach to investigate the antioxidant activity is to develop quantitative structure-activity relationships (QSARs). RESULTS: A curated database of 165 structurally heterogeneous phenolic compounds with the Trolox equivalent antioxidant capacity (TEAC) was developed. Molecular geometries were optimized by means of the GFN2-xTB semiempirical method and diverse molecular descriptors were obtained afterwards. For model development, V-WSP unsupervised variable reduction was used before performing the genetic algorithms-variable subset selection (GAs-VSS) to construct the best five-descriptor multiple linear regression model. The coefficient of determination and the root mean square error were used to measure the performance in calibration (R2 = 0.789 and RMSEC = 0.381), and test set prediction (Q2 = 0.748 and RMSEP = 0.416), along several cross-validation criteria. To thoroughly understand the TEAC prediction, a fully explained mechanism of action of the descriptors is provided. In addition, the applicability domain of the model defined a theoretical chemical space for reliable predictions of new phenolic compounds. CONCLUSION: This in silico model conforms to the five principles stated by the Organisation for Economic Co-operation and Development. The model might be useful for virtual screening of the antioxidant chemical space and for identifying the most potent molecules related to an experimental measurement of TEAC activity. In addition, the model could assist chemists working on computer-aided drug design for the synthesis of new targets with improved activity and potential uses in food science. © 2023 Society of Chemical Industry.
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Antioxidantes , Quimioinformática , Antioxidantes/química , Relación Estructura-Actividad Cuantitativa , Análisis Multivariante , Radicales Libres , FenolesRESUMEN
RESUMEN: Objetivo: Describir el rol de la Salud Oral en las estrategias nacionales y políticas sanitarias para el manejo integral y control de Diabetes Mellitus Tipo 2 (DM2) en los 38 Estados miembros de la Organización para la Cooperación y Desarrollo Económico (OCDE). Materiales y Método: Se realizó una revisión sistemática exploratoria, siguiendo la pauta PRISMA-ScR. Se incluyeron reportes gubernamentales, guías de práctica clínica, documentos oficiales OMS y OCDE, y artículos identificados en PubMED y LiLACS hasta diciembre de 2020. Se sintetizó: 1) Inclusión de la Salud Oral en planes nacionales o guías clínicas de DM2, 2) Prestaciones y cobertura odontológica para DM2 y 3) Indicadores de salud asociados al control de DM2. Resultados: 84 documentos fueron incluidos. 1) La Salud Oral está incorporada en los planes nacionales de 22 países OCDE para el control de DM2. 2) De estos, 8 garantizan la atención odontológica con alta cobertura para DM2. 3) Países OCDE con alta cobertura odontológica presentan los mejores indicadores de control metabólico de DM2. Conclusiones: En el marco de la Salud Global, países que no tienen integrada la salud oral podrían beneficiarse si incorporan la atención odontológica con cobertura universal en el manejo integral y control de la DM2.
ABSTRACT: Aim: To describe the role of Oral Health in national strategies and health policies for the comprehensive management and control of Type 2 Diabetes Mellitus (T2DM) in the 38 member states of the Organization for Economic Cooperation and Development (OECD). Method: A scoping review was carried out, according to the PRISMA-ScR guideline. Government reports, clinical practice guidelines, official WHO and OECD documents, and review articles identified in PubMED and LiLACS were included up to December 2020. The following were synthesized: 1) Inclusion of Oral Health in national plans or clinical guidelines for DM2, 2) Dental benefits and coverage for DM2 and 3) Health indicators associated with the control of DM2. Results: 84 documents were included. 1) Oral Health is incorporated in the national plans of 22 OECD countries for the control of DM2. 2) Of these, 8 provide dental care with high coverage for DM2. 3) OECD countries with high dental coverage have the best indicators of metabolic control of DM2. Conclusions: In the framework of Global Health, countries that do not have Oral Health integrated could benefit if they add dental care in the comprehensive management and control of DM2.
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Humanos , Estrategias de Salud Nacionales , Salud Bucal , Atención Odontológica , Diabetes Mellitus Tipo 2 , Cobertura de los Servicios de Salud , Organización para la Cooperación y el Desarrollo Económico , Política de SaludRESUMEN
Native human skin has been reported in the literature as being an important experimental model for studying skin biology. Studies performed by our group have shown that ex vivo skin, from elective plastic surgery, maintains the biological characteristics of native skin under specific culture conditions. As such, it might be a feasible model for the safety and efficacy testing of topical substances. While Brazil is at the forefront of global regulation implementation, Brazilian researchers are not always able to transfer certain widely used protocols to their laboratories, particularly protocols that involve the use of reconstructed tissues with limited viability, such as those for skin corrosion (OECD TG 431) and irritation testing (OECD TG 439). In this study, we investigated the applicability of the ex vivo skin model to the evaluation of irritation and corrosion potential of a number of proficiency substances described in TG 431 and TG 439. The skin fragments were standardised in size and diameter, and placed into cell culture inserts. The experimental protocol was conducted according to TG 431 and TG 439. The results obtained show that ex vivo skin could represent a promising tool for the evaluation of irritation and corrosion potential of substances (subject to inclusion and exclusion criteria), as recommended by OECD guidelines. While this is a proof-of-concept study, the use of ex vivo skin should be considered for such testing.
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Irritantes , Pruebas de Irritación de la Piel , Alternativas a las Pruebas en Animales , Animales , Corrosión , Humanos , Irritantes/toxicidad , PielRESUMEN
Eleutherine plicata has been shown to be a promising medicinal plant, and its activity has been associated with naphthoquinones. The present study aimed at evaluating the cytotoxicity, genotoxicity, and oral toxicity of the ethanol extract (EEEp), dichloromethane fraction (FDMEp) of E. plicata, and isoeleutherin. For the cytotoxicity evaluation, the viability test (MTT) was used. Genotoxicity was accessed through the Comet assay (alkaline version), acute and subacute oral toxicities were also evaluated. The antioxidant capacity of the samples in the wells where the cells were treated with E. plicata was evaluated. Furthermore, the participation of caspase-8 in the possible mechanism of action of isoeleutherin, eleutherin, and eleutherol was also investigated through a docking study. FDMEp and isoeleutherin were cytotoxic, with higher rates of DNA fragmentation observed for FDMEp and isoeleutherin, and all samples displayed higher antioxidant potential than the control. In the acute oral toxicity test, EEEp, FDMEp, and isoeleutherin did not cause significant clinical changes. In the subacute toxicity assay, EEEp and FDMEp also did not cause clinical, hematological, or biochemical changes. The three compounds bound similarly to caspase-8. Despite the results of cytotoxicity, in vitro studies demonstrated that the use of EEEp appears to be safe and cell death may involve its binding to caspase-8.
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A novel functional drink with nutraceutical properties was formulated from the aqueous extracts of Ilex guayusa, and Vernonanthura patens leaves, and cocoa husks. This juice contains various bioactive compounds, such as phenolic compounds and methylxanthines, with antioxidant and stimulant properties of pharmacological interest. However, it is known whether herbal extracts' interaction may have adverse toxic effects on human health. To evaluate this functional drink's innocuity, we estimated the acute oral toxicity (AOT) in experimental mice. This paper presents the AOT evaluation of two formulations of a functional drink (pre-formulation and microencapsulation) at a single dose of 2000 mg/kg of body weight (b.w.). No signs of adverse toxicity and mortality were observed after a single oral dose of 2000 mg/kg b.w. Likewise, no significant body and organ weight changes, food and water consumption behavior, and no histopathological changes were observed in the main organs evaluated. In conclusion, this functional drink can be categorized as low toxicity " according to the Globally Harmonized Classification System (GHS), making it a potential beverage with high nutritional and pharmacological value.
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Three-dimensional skin models, also named 3D skin models, human skin equivalents (HSEs), or Human Epidermal Equivalents (HEEs), have been increasingly used for chemical assessments in terms of efficacy and safety. Considering this, we developed an HEE model using immortalized HaCaT cells, aiming to overcome the limitation of primary tissue source. Our 3D model (HaCaT-HEE) exhibited important markers of cell differentiation (CK10, CK14, involucrin, and filaggrin), although the stratum corneum was shown to be modest. Besides, the model showed a good prediction potential considering membrane permeability, sensitivity, specificity, and accuracy in distinguishing irritant and corrosive effects after exposure to selected chemicals recommended by the OECD protocols. We also validated the formazan determination for the MTT method using High-Performance Liquid Chromatography (HPLC). For that, we considered carry over, linearity, reproducibility/robustness, accuracy, precision, selectivity, and matrix effect, according to the Food and Drug Administration (FDA) guideline. Based on our results, we can conclude that our model has an acceptable predictive value for the safety evaluation of compounds after skin exposure, with the great advantage of being constructed using immortalized cells.
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Cáusticos/toxicidad , Irritantes/toxicidad , Queratinocitos/efectos de los fármacos , Pruebas de Irritación de la Piel/métodos , Alternativas a las Pruebas en Animales , Línea Celular , Permeabilidad de la Membrana Celular/efectos de los fármacos , Epidermis , Proteínas Filagrina , HumanosRESUMEN
The safety and bioactive potential of crude carotenoid extract from Cantaloupe melon nanoencapsulated in porcine gelatin (EPG) were evaluated in a chronic inflammatory experimental model. Animals were fed a high glycemic index and high glycemic load (HGLI) diet for 17 weeks and treated for ten days with 1) HGLI diet, 2) standard diet, 3) HGLI dietâ¯+â¯crude carotenoid extract (CE) (12.5â¯mg/kg), and 4) HGLI dietâ¯+â¯EPG (50â¯mg/kg). General toxicity signals were investigated, considering body weight, food intake, hematological, biochemical parameters, relative weight, morphology, and histopathology of organs. The biochemical parameters indicated the low toxicity of EPG. Acute hepatitis was observed in animals' livers, but CE and EPG groups presented improved tissue appearance. Chronic enteritis was observed in animals, with villi and intestinal glands preservation in the EPG group. The results suggest the safety and the bioactive effect of EPG, possibly related to its anti-inflammatory potential.
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The study of international collaborations can help in understanding the benefits of such relationships and aid in developing national financing policies. In this paper, the international collaboration of Brazilian scientists was studied using SciVal® and Incites® database, looking at its effect on the universities, financing agencies and different areas of knowledge and research topic clusters. Cluster and principal component analyses of scientometric data were carried out. While the results confirmed known knowledge that international collaboration increases impact, this study shows that Brazilian researchers are contributing to prominent research topics worldwide, in all areas of knowledge. This finding is contrary to several points of view that identify Brazil as a regional and not an international partner in science. Important also to note the impact of Brazilian authors in international collaboration that is well above the world mean. The collaboration of Brazil with foreign partners brings benefits for both sides, creating the opportunity of Brazilian research access to financing from international agencies. Increases in measures of impact are also seen for both sides. Foreign partners likewise benefit from higher impact factors in the same topic cluster, when collaborating with Brazilian partners. Publishing open access in high impact journals is fundamental for maintaining Brazilian science at the forefront.
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The human immunodeficiency virus is a lethal pathology considered as a worldwide problem. The search for new strategies for the treatment of this disease continues to be a great challenge in the scientific community. In this study, a series of 107 derivatives of 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine, previously evaluated experimentally against HIV-I reverse transcriptase, was used to model antiretroviral activity. A model of linear regression, implemented in the QSARINS software, was developed with a genetic algorithm for variable selection. The fit of its parameters was good and exhaustive validation, according to the OECD regulatory principles, was performed. Also, the applicability domain was established. In addition, its robustness (r 2 = 0.84), stability (Q 2 LOO = 0.81; Q 2 LMO = 0.80) and good predictive power (r 2 EXT = 0.85) is proved. So, it was used to predict the antiretroviral activity of eight compounds obtained by rational drug design. Finally, it can be affirmed that the proposed tools allow the rapid and economic identification of potential antiretroviral drugs.
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Antirretrovirales/química , Relación Estructura-Actividad Cuantitativa , Timina/análogos & derivados , Modelos Químicos , Organización para la Cooperación y el Desarrollo Económico/normas , Timina/químicaRESUMEN
Introduction: Payment mechanisms serve to put into operation the function of purchasing in health. Payment mechanisms impact the decisions that healthcare providers make. Given this, we are interested in knowing how they affect the generalized increase of C-section rates globally. Objective: The objective of this review is to describe existing payment mechanisms for childbirth in countries members of the Organization for Economic Co-operation and Development (OECD) and non-members. Methods: We conducted a scoping review following the five methodological steps of the Joanna Briggs Institute. The search was conducted by researchers independently, achieving inter-reliability among raters (kappa index, 0.96). We searched electronic databases, grey literature, and governmental and non-governmental websites. We screened on three levels and included documents published in the last ten years, in English and Spanish. Results were analyzed considering the function of the reimbursement mechanism and its effects on providers, payers, and beneficiaries. Results: Evidence from 34 countries was obtained (50% OECD members). Sixty-four percent of countries report the use of more than one payment mechanism for childbirth. Diagnosis-Related Groups (47.6%), Pay-for-performance (23.3%), Fee-for-service (16.6%) and Fixed-prospective systems (13.3%) are among the most frequently used mechanisms. Conclusion: Countries use payment mechanism architecture to improve maternal-perinatal health indicators. Therefore, it is necessary to explore the best combination of mechanisms that improve the provision of health care and welfare of the population in the field of sexual and reproductive health.
Introducción: Los mecanismos de pago corresponden a la operacionalización de la función de compra en salud, incentivando comportamientos en los proveedores de servicios sanitarios. Resulta pertinente preguntarse cómo afectan la vía de resolución del parto, considerando el aumento generalizado en índices de cesárea a nivel global. Objetivo: Describir los mecanismos de pago existentes para la atención del parto en países miembros y no miembros de la Organización para la Cooperación y el Desarrollo Económico. Métodos: Revisión sistemática exploratoria (scoping review). Se adoptaron los cinco pasos metodológicos del Joanna Briggs Institute. La búsqueda se realizó por las investigadoras de forma independiente, logrando la confiabilidad interevaluador (κ 0,96) en bases de datos electrónicas, otras fuentes de información, sitios web gubernamentales y no gubernamentales. Se tamizó en tres niveles, considerando literatura no mayor a 10 años de anti-güedad, idioma inglés y español. Se analizaron los resultados considerando el funcionamiento del mecanismo de pago y sus efectos en prestado-res, seguros y beneficiarias. Resultados: Se obtuvo evidencia de 34 países (50% pertenecientes a la Organización para la Cooperación y el Desarrollo Económico). El 64% con uso de más de un mecanismo de pago para el parto. Entre los mecanismos más utilizados están: grupos relacionados de diagnósticos (47,6%), pago por resultados (23,3%), pago por servicios (16,6%) y pago fijo prospectivo (13,3%). Conclusión: Los países recurren a la arquitectura de los mecanismos de pago para mejorar indicadores en salud materno-perinatales. Es necesario explorar cuál sería la mejor combinación de mecanismos que mejora la provisión de atenciones de salud y bienestar de la población, en el campo de la salud sexual y reproductiva.
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Cesárea/economía , Atención a la Salud/economía , Parto Obstétrico/economía , Cesárea/estadística & datos numéricos , Planes de Aranceles por Servicios/economía , Femenino , Humanos , Organización para la Cooperación y el Desarrollo Económico , Embarazo , Reembolso de Incentivo/economíaRESUMEN
The zebrafish (Danio rerio) is a small teleost fish that is becoming increasingly popular in laboratories worldwide and several attributes have also placed the zebrafish under the spotlight of (eco)toxicological studies. Since the 1990s, international organizations such as ISO and OECD have published guidelines for the use of zebrafish in ecotoxicological assessment of environmental toxicants such as the Fish Embryo Acute Toxicity (FET) test, OECD n° 236 guideline. This protocol uses 3,4-dichloroaniline (DCA), an aniline pesticide whose toxicity to fish species at early life stages is well known, as a positive control. Despite its use, little is known about its molecular mechanisms, especially in the context of the FET test. Therefore, this study aimed to investigate such changes in zebrafish larvae exposed to DCA (4 mg/L) for 96 hours using gel-free proteomics. Twenty-four proteins detected in both groups were identified as significantly affected by DCA exposure, and, when considering group-specific entities, 48 proteins were exclusive to DCA (group-specific proteins) while 248 were only detected in the control group. Proteins modulated by DCA treatment were found to be involved in metabolic processes, especially lipids and hormone metabolism (eg, Apoa1 and Apoa1b and vitelogenins), as well as proteins important for developmental processes and organogenesis (eg, Myhc4, Acta2, Sncb, and Marcksb). The results presented here may therefore provide a better understanding of the relationships between molecular changes and phenotype in zebrafish larvae treated with DCA, the reference compound of the FET test.
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Compuestos de Anilina/toxicidad , Contaminantes Químicos del Agua/toxicidad , Animales , Ecotoxicología , Embrión de Mamíferos , Embrión no Mamífero/metabolismo , Larva , Proteómica , Pruebas de Toxicidad Aguda , Pez Cebra/metabolismoRESUMEN
In recent years, in-vitro skin models for chemical hazard identification have been developed. Most of them consist only of human keratinocytes, neglecting the contribution of other skin constituents. Cultures containing the dermal and epidermal component provide an attractive system to investigate, in a more realistic model, toxicological responses, which represents a distinct advantage over keratinocytes-based models that do not mimic faithfully the in vivo environment. This study aimed to validate dermo-epidermal organotypic cultures (ORGs) as a platform to perform irritation and corrosion tests. Skin models were constructed by seeding keratinocytes on fibroblast-containing fibrin gels. After 21â¯days, the ORGs were evaluated histologically, and the irritant and corrosion potential was determined by means of viability measurements (MTT assay) and cytokine release, according to 431 and 439 OECD tests guidelines. Skin models showed similar histological characteristics to native skin and were able to classify different substances with high accuracy, showing their applicability to skin irritation and corrosion tests. Although cytokines release seems to be chemical-dependent, a tendency was observed, leading to the improvement of the prediction capacity. Nevertheless, further studies should be done to reduce variability in order to increase prediction capacity.
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Cáusticos/toxicidad , Irritantes/toxicidad , Pruebas de Irritación de la Piel , Técnicas de Cultivo de Tejidos , Alternativas a las Pruebas en Animales , Cáusticos/clasificación , Supervivencia Celular/efectos de los fármacos , Citocinas/metabolismo , Fibrina , Fibroblastos/efectos de los fármacos , Geles , Humanos , Irritantes/clasificación , Queratinocitos/efectos de los fármacos , Modelos Biológicos , Piel/efectos de los fármacosRESUMEN
The lack of predictivity of animal's models has increased the failure rate of drug candidates. Thus, the reversion of this scenario using preliminary in vitro assays and metabolism prediction can reduce the unnecessary use of animals, as well as predict toxic effects at preclinical and clinical stages. The present study aimed to evaluate safety of four biologically active molecules (RN104, RI78, ICH, PCH) with potential therapeutic applications synthesized in our laboratory. Initially, we used MTT cytotoxicity against A549, H9C2, HepG2, LLC-PK1 and NEURO-2 cell lines. RN104 showed the lowest cytotoxicity and further studies were conducted with it. The neutral red (NR) test was performed according to OECD-129 and then acute toxicity test (OECD-423). According to NR results we administered at 300 mg/kg on animals; however, no toxic effect was observed, while 2,000 mg/kg resulted in the death of one animal per group. After, metabolism prediction studies, performed using both ligand-based and structure-based, suggests three potential metabolites. In silico results suggested that potential metabolites could be fast eliminated and, then, this could be an explanation for lower observed toxicity in in vivo experiments. The results showed limitations of the NR as a predictor of the initial dose for the acute toxicity study, which may be related to metabolism. Therefore, the combination of theoretical and experimental studies is relevant to a general understanding of new molecule's toxicity.
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Citotoxinas/farmacología , Células 3T3 , Células A549 , Animales , Línea Celular , Línea Celular Tumoral , Evaluación Preclínica de Medicamentos/métodos , Femenino , Células Hep G2 , Humanos , Ratones , Modelos Animales , Rojo Neutro/metabolismo , Pruebas de Toxicidad Aguda/métodosRESUMEN
The metal-organic framework (MOF) [Eu(DPA)(HDPA)] (where DPA is dipicolinic acid) has been previously reported as an efficient marker for gunshot residues (GSRs). Since this marker will be in contact with various shooters, industrial workers, and the environment, however, it is important to identify its toxicity. In this work, the oral and the inhalation acute toxicities of the MOF [Eu(DPA)(HDPA)] (also called R-Marker) were evaluated in young Wistar rats using Guidelines 423 (oral) and 436 (inhalation) from the Organisation for Economic Co-operation and Development (OECD). Animal behavior; body weight, water, and food intake; and organ weight, as well as biochemical parameters were evaluated in both evaluations. For the inhalation test, a concentration of 1 mg·Lair-1·(4 h-1) was reached in a whole-body inhalation chamber. When the respiratory tract was analyzed, it was observed that part of the marker had been swallowed instead of inhaled by the animal. For the oral test, the highest administrated dose was 2000 mg/kg with no sign of toxicity. This marker has been classified in the least toxic category of the Globally Harmonized System (GHS; category 5), with an oral median lethal dose (LD50) of 5000 mg/kg. After the oral administration, the feces of the animals were collected using a metabolic cage. Luminescent feces were present up to 24 h after administration, indicating that the marker had been excreted by the organism without causing intoxication. This study has opened perspectives for drug delivery and toxicity studies, since it enables visual detection of the marker.
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INTRODUCCIÓN Los mecanismos de pago corresponden a la operacionalización de la función de compra en salud, incentivando comportamientos en los proveedores de servicios sanitarios. Resulta pertinente preguntarse cómo afectan la vía de resolución del parto, considerando el aumento generalizado en índices de cesárea a nivel global. OBJETIVO: Describir los mecanismos de pago existentes para la atención del parto en países miembros y no miembros de la Organización para la Cooperación y el Desarrollo Económico. MÉTODOS: Revisión sistemática exploratoria (scoping review). Se adoptaron los cinco pasos metodológicos del Joanna Briggs Institute. La búsqueda se realizó por las investigadoras de forma independiente, logrando la confiabilidad interevaluador (κ 0,96) en bases de datos electrónicas, otras fuentes de información, sitios web gubernamentales y no gubernamentales. Se tamizó en tres niveles, considerando literatura no mayor a 10 años de antigüedad, idioma inglés y español. Se analizaron los resultados considerando el funcionamiento del mecanismo de pago y sus efectos en prestado-res, seguros y beneficiarias. RESULTADOS: Se obtuvo evidencia de 34 países (50% pertenecientes a la Organización para la Cooperación y el Desarrollo Económico). El 64% con uso de más de un mecanismo de pago para el parto. Entre los mecanismos más utilizados están: grupos relacionados de diagnósticos (47,6%), pago por resultados (23,3%), pago por servicios (16,6%) y pago fijo prospectivo (13,3%). CONCLUSIÓN: Los países recurren a la arquitectura de los mecanismos de pago para mejorar indicadores en salud materno-perinatales. Es necesario explorar cuál sería la mejor combinación de mecanismos que mejora la provisión de atenciones de salud y bienestar de la población, en el campo de la salud sexual y reproductiva.
INTRODUCTION: Payment mechanisms serve to put into operation the function of purchasing in health. Payment mechanisms impact the decisions that healthcare providers make. Given this, we are interested in knowing how they affect the generalized increase of C-section rates globally. OBJECTIVE: The objective of this review is to describe existing payment mechanisms for childbirth in countries members of the Organization for Economic Co-operation and Development (OECD) and non-members. METHODS: We conducted a scoping review following the five methodological steps of the Joanna Briggs Institute. The search was conducted by researchers independently, achieving inter-reliability among raters (kappa index, 0.96). We searched electronic databases, grey literature, and governmental and non-governmental websites. We screened on three levels and included documents published in the last ten years, in English and Spanish. RESULTS: were analyzed considering the function of the reimbursement mechanism and its effects on providers, payers, and beneficiaries. Results Evidence from 34 countries was obtained (50% OECD members). Sixty-four percent of countries report the use of more than one payment mechanism for childbirth. Diagnosis-Related Groups (47.6%), Pay-for-performance (23.3%), Fee-for-service (16.6%) and Fixed-prospective systems (13.3%) are among the most frequently used mechanisms. CONCLUSION: Countries use payment mechanism architecture to improve maternal-perinatal health indicators. Therefore, it is necessary to explore the best combination of mechanisms that improve the provision of health care and welfare of the population in the field of sexual and reproductive health.
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Humanos , Femenino , Embarazo , Cesárea/economía , Parto Obstétrico/economía , Atención a la Salud/economía , Reembolso de Incentivo/economía , Cesárea/estadística & datos numéricos , Planes de Aranceles por Servicios/economía , Organización para la Cooperación y el Desarrollo EconómicoRESUMEN
This paper provides empirical evidence of the existence of a long-run causal relationship between GDP and health care expenditures, for a group of Latin American and the Caribbean countries and for OECD countries for the period 1995-2014. We estimated the income elasticity of health expenditure to be equal to unity for both groups of countries, that is, health care in Latin American and OECD countries is a necessity rather than a luxury. We did not find evidence of a causal effect in the opposite direction, i.e. from changes in health expenditure to GDP. We present conclusive evidence of the cross-country dependence of the analyzed series, and consequently we used panel unit root tests, panel cointegration tests, and long-run estimates that are robust to such dependence. Specifically, we use the CIPS panel unit root test and the panel Common Correlated Effects estimator. We also show that the results obtained by mistakenly using methods that assume cross-section independence are unstable.
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Producto Interno Bruto , Gastos en Salud , Organización para la Cooperación y el Desarrollo Económico , América Latina , Modelos EconométricosRESUMEN
The steps followed in the knowledge discovery in databases (KDD) process are well documented and are widely used in different areas where exploration of data is used for decision making. In turn, while different workflows for developing quantitative structure-activity relationship (QSAR) models have been proposed, including combinatorial use of QSAR, there is now agreement on common requirements for building trustable predictive models. In this work, we analyze and confront the steps involved in KDD and QSAR and present how they comply with the OECD principles for the validation, for regulatory purposes, of QSAR models.