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Abstract Introduction: Multipurpose solutions (MPS) for soft contact lenses (SCL) play an essential role in inhibiting potentially pathogenic agents. Their antimicrobial effectiveness is assessed in vitro and their safety in vivo, with clinical trials that include a combination of different solutions and lens materials. The objective is to assess the biocompatibility of a new SCL MPS produced in Colombia that contains polyhexamethylene biguanide (PHMB) and to determine its antimicrobial activity. Materials and Methods: This was a crossover study with 25 subjects who did not wear lens and who were fitted with different combinations of five SCL materials with either MPS or control physiological saline solution (CS). Corneal thickness, conjunctival hyperemia, corneal staining, and comfort were assessed after two hours of wearing SCL. Antimicrobial effectiveness was measured using ISO 14729 standard assays. Results: When considering SCL material, there was a statistically significant difference between the new MPS and the CS for Comfilcon A (p < 0.05). There was no statistical or clinically significant difference for corneal thickness or corneal staining between the combination of lens material and new MPS with the CS (p > 0.05). After two hours of lens insertion, comfort scores were higher than 7.8. The MPS reduced bacteria colony forming units (CFU) in over 3 log, and fungal CFU in over 1.0 log. Conclusions: The new MPS met the antimicrobial standards of ISO 14729, is considered safe and biocompatible with the ocular surface and retains high comfort levels.
Resumen Introducción: las soluciones multipropósito (SMP) para lentes de contacto blandos (LCB) desempeñan un papel esencial en la inhibición de agentes potencialmente patógenos. Su efectividad antimicrobiana se evalúa in vitro, y su seguridad, in vivo, con ensayos clínicos que incluyen una combinación de diferentes soluciones y materiales para lentes. El objetivo es evaluar la biocompatibilidad de una nueva SMP producida en Colombia que contiene polihexametileno biguanida (PHMB) y determinar su actividad antimicrobiana. Materiales y métodos: estudio cruzado con 25 sujetos no usuarios de lentes, que fueron adaptados con cinco combinaciones diferentes de materiales de LCB con una nueva SMP o solución salina fisiológica de control (CS). El grosor corneal, la hiperemia conjuntival, la tinción corneal y la comodidad se evaluaron después de dos horas de uso del LC. La efectividad antimicrobiana se midió utilizando ensayos estándar ISO 14729. Resultados: considerando el material del LCB, solo hubo una diferencia estadísticamente significativa entre la nueva SMP y el CS para el Comfilcon A (p < 0.05). Tampoco hubo diferencias estadísticamente o clínicamente significativas para el grosor corneal o la tinción corneal, entre la combinación del material del lente y la nueva SMP con el CS (p > 0.05). Después de dos horas de uso del lente, las puntuaciones de confort fueron superiores a 7.8. La SMP redujo las unidades formadoras de colonias (UFC) de bacterias en más de 3 log, y las UFC fúngicas en más de 1.0 log. Conclusiones: la nueva SMP cumplió con los estándares antimicrobianos de ISO 14729, y se considera segura y biocompatible con la superficie ocular, con altos niveles de confort.
Resumo Introdução: as soluções multipropósito (SMP) para lentes de contato macias (LCM) apresentam um papel essencial na inibição de agentes potencialmente patógenos. Sua eficácia como agente antimicrobiano se valia in vitro, e sua segurança, in vivo, como ensaios clínicos que incluem uma combinação de diferentes soluções e materiais para lentes. O objetivo é avaliar a biocompatibilidade de uma nova SMP produzida na Colômbia a base de polihexametileno biguanida (PHMB) e determinar seu potencial antimicrobiano. Materiais e métodos: estudo cruzado com 25 indivíduos não usuários de lentes, que foram adaptados com cinco combinações diferentes de LCM como uma nova SMP ou solução salina fisiológica como controle (CS). A espessura da córnea, a hiperemia conjuntival, a coloração da córnea e a comodidade, foram avaliadas após duas horas de uso da LCB. A eficácia antimicrobiana foi medida com ensaios padrão ISO 14729. Resultados: considerando o material da LCB, houve apenas uma diferença estatisticamente significativa entre a nova SMP e o CS, paro o Comfilcon A (p <0.05). Não houve diferença estatisticamente ou clinicamente significativa para a espessura da córnea ou a coloração da córnea, entre a combinação do material da lente e a nova SMP com o controle CS (p > 0.05). Após duas horas de uso, as pontuações de conforto foram superiores a 7,8. A SMP reduziu as unidades formadoras de colônias (UFC) de bactérias em mais de 3 log, e as UFC fúngicas em mais de 1.0 log. Conclusões: a nova SMP cumpriu com os padrões antimicrobianos ISO 14729, é considerada segura e biocompatível com a superfície ocular, com altos níveis de conforto.
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Humanos , Lentes de Contato Hidrofílicas , Hiperemia , Células-TroncoRESUMO
INTRODUCTION: The efficacy of immune checkpoint inhibitors in patients with brain metastases (BMs) from non-oncogene addicted non-small cell lung cancer (NSCLC) is under investigation. Here, we sought to determine the optimal management of NSCLCs with PD-L1 ≥ 50% and asymptomatic BMs who were treated with first-line pembrolizumab. METHODS: Thirty patients from 15 institutions with PD-L1 ≥ 50% NSCLC had asymptomatic BMs, and met inclusion criteria. Patients were classified based on whether they had undergone upfront local radiotherapy for BMs as well as on the type of brain radiotherapy received. RESULTS: Nine patients were treated with upfront pembrolizumab alone, 8 patients with whole-brain radiotherapy (WBRT) followed by pembrolizumab and 13 patients with stereotactic radiosurgery (SRS) followed by pembrolizumab. Patients' characteristics were similar among the three groups of patients except for a higher number of BMs ≥ 3 in the WBRT group. One complete and 4 partial intracranial responses were observed with upfront pembrolizumab alone. The median survival was not reached for the pembrolizumab and WBRT (n = 8) groups, and it was 7.6 months for the SRS (n = 13) group (P = 0.09), with 12-month survival rates being 55.5%, 62.5%, and 23.0%, respectively. Salvage WBRT was delivered in 1 patient in the upfront pembrolizumab group and in 4 patients in the SRS group. CONCLUSIONS: Upfront pembrolizumab showed efficacy in selected patients with PD-L1 ≥ 50% non-oncogene addicted NSCLC and asymptomatic BMs. Prospective studies should address whether pembrolizumab alone, and deferral of radiotherapy, could be pursued in this patient population.
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Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Doenças Assintomáticas , Antígeno B7-H1/metabolismo , Neoplasias Encefálicas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/efeitos adversos , Antineoplásicos Imunológicos/efeitos adversos , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/secundário , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Carcinoma Pulmonar de Células não Pequenas/secundário , Irradiação Craniana/métodos , Feminino , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Radiocirurgia/estatística & dados numéricos , Estudos Retrospectivos , Terapia de Salvação/métodos , Resultado do TratamentoRESUMO
The disinfection of helminth eggs and Escherichia coli contaminated aqueous solutions, was studied using an electro-Fenton reactor equipped with a polarized activated carbon (AC) packed bed and two chambers loaded with cation exchange resins. Experiments using different arrangements and operation conditions, revealed that effective elimination of Escherichia coli takes place in all electrochemical disinfection tests. For the more resistant helminth eggs however, adsorption, electro-oxidation and electro-Fenton experiments showed retention within the reactor and pathogen inactivation values of 0, 16, and 25%, respectively. Using helminth eggs concentration data in different sections of the reactor, optical microscopy analysis and an exploratory computer simulation, differences in the disinfection performance were explained and new recirculation and flow direction and polarization switching operation schemes were defined. The corresponding experiments revealed that the effective coupling between adsorption and electro-Fenton phenomena, all along the AC packed bed compartment, results in 100% inactivation of helminth eggs.
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Desinfecção/métodos , Helmintos , Eliminação de Resíduos Líquidos/métodos , Animais , Carvão Vegetal , Simulação por Computador , Escherichia coli , Humanos , Peróxido de Hidrogênio/química , Oxirredução , Águas ResiduáriasRESUMO
Next-generation ALK TKIs have become the new standard of care in first-line setting in advanced ALK-positive NSCLC patients. However, sequential strategies at progression are relevant, as may have an impact on patients' outcome. In this commentary we discuss whether genomic-tailored strategies at progression would be more suitable for improving outcome of ALK-positive NSCLC patients.
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Quinase do Linfoma Anaplásico/antagonistas & inibidores , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Mutação , Inibidores de Proteínas Quinases/uso terapêutico , Quinase do Linfoma Anaplásico/genética , Carcinoma Pulmonar de Células não Pequenas/enzimologia , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Resistencia a Medicamentos Antineoplásicos , Humanos , Neoplasias Pulmonares/enzimologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Medicina de Precisão/métodosRESUMO
Compound databases of natural products have a major impact on drug discovery projects and other areas of research. The number of databases in the public domain with compounds with natural origins is increasing. Several countries, Brazil, France, Panama and, recently, Vietnam, have initiatives in place to construct and maintain compound databases that are representative of their diversity. In this proof-of-concept study, we discuss the first version of BIOFACQUIM, a novel compound database with natural products isolated and characterized in Mexico. We discuss its construction, curation, and a complete chemoinformatic characterization of the content and coverage in chemical space. The profile of physicochemical properties, scaffold content, and diversity, as well as structural diversity based on molecular fingerprints is reported. BIOFACQUIM is available for free.
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Produtos Biológicos/química , Bases de Dados de Compostos Químicos , Descoberta de Drogas , MéxicoRESUMO
Background: Natural product databases are important in drug discovery and other research areas. An analysis of its structural content, as well as functional group occurrence, provides a useful overview, as well as a means of comparison with related databases. BIOFACQUIM is an emerging database of natural products characterized and isolated in Mexico. Herein, we discuss the results of a first systematic functional group analysis and global diversity of an updated version of BIOFACQUIM. Methods: BIOFACQUIM was augmented through a literature search and data curation. A structural content analysis of the dataset was performed. This involved a functional group analysis with a novel algorithm to automatically identify all functional groups in a molecule and an assessment of the global diversity using consensus diversity plots. To this end, BIOFACQUIM was compared to two major and large databases: ChEMBL 25, and a herein assembled collection of natural products with 169,839 unique compounds. Results: The structural content analysis showed that 15.7% of compounds and 11.6% of scaffolds present in the current version of BIOFACQUIM have not been reported in the other large reference datasets. It also gave a diversity increase in terms of scaffolds and molecular fingerprints regarding the previous version of the dataset, as well as a higher similarity to the assembled collection of natural products than to ChEMBL 25, in terms of diversity and frequent functional groups. Conclusions: A total of 148 natural products were added to BIOFACQUIM, which meant a diversity increase in terms of scaffolds and fingerprints. Regardless of its relatively small size, there are a significant number of compounds and scaffolds that are not present in the reference datasets, showing that curated databases of natural products, such as BIOFACQUIM, can serve as a starting point to increase the biologically relevant chemical space.
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Produtos Biológicos , Bases de Dados de Compostos Químicos , Descoberta de Drogas , MéxicoRESUMO
Scaffold analysis of compound data sets has reemerged as a chemically interpretable alternative to machine learning for chemical space and structure-activity relationships analysis. In this context, analog series-based scaffolds (ASBS) are synthetically relevant core structures that represent individual series of analogs. As an extension to ASBS, we herein introduce the development of a general conceptual framework that considers all putative cores of molecules in a compound data set, thus softening the often applied "single molecule-single scaffold" correspondence. A putative core is here defined as any substructure of a molecule complying with two basic rules: (a) the size of the core is a significant proportion of the whole molecule size and (b) the substructure can be reached from the original molecule through a succession of retrosynthesis rules. Thereafter, a bipartite network consisting of molecules and cores can be constructed for a database of chemical structures. Compounds linked to the same cores are considered analogs. We present case studies illustrating the potential of the general framework. The applications range from inter- and intra-core diversity analysis of compound data sets, structure-property relationships, and identification of analog series and ASBS. The molecule-core network herein presented is a general methodology with multiple applications in scaffold analysis. New statistical methods are envisioned that will be able to draw quantitative conclusions from these data. The code to use the method presented in this work is freely available as an additional file. Follow-up applications include analog searching and core structure-property relationships analyses.
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Persistent organic pollutants (POPs) were assessed for the first time in blue whales from the South Pacific Ocean. Concentrations of polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), hexachlorobenzene (HCB) and dichlorodiphenyltrichloroethane and its main metabolites (DDTs), were determined in 40 blubber samples from 36 free-ranging individuals and one stranded, dead animal along the coast of southern Chile between 2011 and 2013. PCBs were the most abundant pollutants (2.97-975â¯ng/g l.w.), followed by DDTs (3.50-537â¯ng/g l.w.), HCB (nd-77.5â¯ng/g l.w.) and PBDEs (nd-33.4â¯ng/g l.w). There was evidence of differences between sexes, with lower loads in females potentially due to pollutants passing to calves. POP concentrations were higher in specimens sampled in 2013; yet, between-year differences were only statistically significant for HCB and PBDEs. Lower chlorinated (pentaâ¯>â¯tetraâ¯>â¯tri) and brominated (tetraâ¯>â¯tri) congeners were the most prevalent among PCBs and PBDEs, respectively, mostly in agreement with findings previously reported in blue and other baleen whales. The present study provides evidence of lower levels of contamination by POPs in eastern South Pacific blue whales in comparison to those reported for the Northern Hemisphere.
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Tecido Adiposo/metabolismo , Balaenoptera/metabolismo , Monitoramento Ambiental , Poluentes Químicos da Água/metabolismo , Animais , Chile , DDT/metabolismo , Feminino , Éteres Difenil Halogenados/metabolismo , Hexaclorobenzeno/metabolismo , Hidrocarbonetos Clorados/metabolismo , Masculino , Oceano Pacífico , Bifenilos Policlorados/metabolismoRESUMO
Naturally occurring small molecules include a large variety of natural products from different sources that have confirmed activity against epigenetic targets. In this work we review chemoinformatic, molecular modeling, and other computational approaches that have been used to uncover natural products as inhibitors of DNA methyltransferases, a major family of epigenetic targets with therapeutic interest. Examples of computational approaches surveyed in this work are docking, similarity-based virtual screening, and pharmacophore modeling. It is also discussed the chemoinformatic-guided exploration of the chemical space of naturally occurring compounds as epigenetic modulators which may have significant implications in epigenetic drug discovery and nutriepigenetics.
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AIM: This cross-sectional study evaluated liver fibrosis in patients with non-alcoholic fatty liver disease (NAFLD), and compared the characteristics of metabolically healthy obese (MHO) with metabolically unhealthy obese (MUHO) patients. METHODS: The study was nested within a randomized clinical trial (RCT) and included obese patients with NAFLD, as determined by liver ultrasonography. Fibrosis was assessed by transient elastography, and AST-to-platelet ratio index (APRI) and NAFLD score. Patients were compared according to obesity phenotype using various accepted criteria. RESULTS: The RCT included 1024 patients with NAFLD, of whom 428 (41.7%) were included in the present study. The prevalence of MHO ranged from 1.2% to 63%, depending on the criteria used. According to various criteria for metabolic health, obese patients had less liver fibrosis. MHO patients, as defined by all criteria, showed a significantly lower prevalence of advanced liver fibrosis (F3-F4) than MUHO on transient elastography (16.5% vs. 28%, respectively; P≤0.05). CONCLUSION: MUHO patients are at higher risk of liver fibrosis and, therefore, the identification of obese patients with 'healthy' characteristics is imperative as their entire clinical work-ups are likely to differ.