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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.
Assuntos
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.
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Cirrose Hepática/patologia , Fígado/patologia , Hepatopatia Gordurosa não Alcoólica/patologia , Obesidade/patologia , Adulto , Índice de Massa Corporal , Técnicas de Imagem por Elasticidade , Feminino , Humanos , Fígado/diagnóstico por imagem , Cirrose Hepática/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/diagnóstico por imagem , Obesidade/diagnóstico por imagem , UltrassonografiaRESUMO
Introduction: Gastric cancer (GC) is the leading cause of cancer mortality in Chile. The development ofgastric adenocarcinoma its preceded by a histopathologic cascade composed of gastric atrophy, intestinal metaplasia and gastric dysplasia. Sydney protocol has been proposed as the standard method for diagnosingthese conditions. The aim of this research study was to establish whether Sydney protocol increase thedetection of premalignant gastric lesions, as gastric atrophy and intestinal metaplasia, compared to non protocolizedendoscopies/biopsies. Methods: Upper gastroduodenal endoscopies (GDE) from Hospital Clí-nico Universidad Católica de Chile between April-May 2015 and April-May 2016 was analyzed. Patientswith histological study with 18 years-old or older were included. Patients with history of GC or malignantlesions at GDE where excluded. Detection of gastric atrophy, intestinal metaplasia and suggestive findingsof autoimmune gastritis where compared between Sydney protocol and non-protocolized endoscopies/biopsies...
Introducción: El cáncer gástrico (CG) es la principal causa de muertes por cáncer en Chile. El desarrollo del adenocarcinoma gástrico es precedido por una cascada histopatológica (gastritis; atrofia gástrica/AG; metaplasia intestinal/MI). Se ha propuesto la biopsia del cuerpo, ángulo y antro a través del protocolo de Sydney para la búsqueda de estas condiciones. Objetivo: Determinar la diferencia en la detección delesiones premalignas gástricas a través del protocolo de Sydney comparado con el estudio endoscópico habitual. Métodos: Se analizaron las endoscopias digestivas altas (EDA) realizadas en el Centro de Endoscopia Digestiva del Hospital Clínico de la Universidad Católica en los períodos entre abril y mayo del 2015 y 2016. Se incluyeron las EDA de pacientes mayores de 18 años con estudio histológico. Fueron excluidos los pacientes con antecedente personal de CG o lesiones de aspecto maligno macroscópicas. Se comparó la detección de AG, MI y gastritis autoinmune (GA) en el estudio histológico entre los pacientes con protocolo Sydney y el estudio endoscópico no protocolizado...
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Masculino , Feminino , Humanos , Adulto , Adulto Jovem , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Biópsia/métodos , Lesões Pré-Cancerosas/patologia , Neoplasias Gástricas/patologia , Atrofia/patologia , Chile , Protocolos Clínicos , Endoscopia do Sistema Digestório , Infecções por Helicobacter/patologia , Metaplasia/patologia , Estudos RetrospectivosRESUMO
In this work, a suite of diagnostic biomarkers was applied to seven cetacean species to evaluate the role of the feeding habits and migratory behavior in the toxicological status of these species from the Gulf of California, Mexico. We investigate the interspecific differences in cytochrome P450 1A1 and 2B (CYP1A1 and CYP2B, respectively), aryl hydrocarbon receptor and E2F transcription factor 1 and the contaminants levels [organochlorine compounds, polybrominated diphenyl ethers (PBDEs) and polycyclic aromatic hydrocarbons (PAHs)] in four odontocete species (common bottlenose dolphin, long-beaked common dolphin, sperm whale and killer whale) and three mysticete species (blue whale, fin whale, and Bryde's whale) using skin biopsy. Differences in contaminant levels and molecular biomarker responses between the odontocete and mysticete species have been pointed out. The canonical discriminant analysis on principal component analysis factors, performed to reveal clustering variables, shows that odontocete are characterised by the highest levels of lipophilic contaminants compared to the mysticete, with the highest levels of polychlorinated biphenyls, dichlorodiphenyltrichloroethanes and PBDEs detected in killer whale and the lowest levels in Bryde's whale. The biomarker data show interspecific differences amongst the seven species, revealing highest CYP1A and CYP2B protein levels in the mysticete fish-eating species (Bryde's whale). In conclusion, three main factors seem to regulate the biomarker responses in these species: (a) the inductive ability of persistent organic pollutants and PAHs; (b) the different evolutionary process of the two CYPs related to the different feeding habits of the species; (c) the migratory/resident behaviour of the mysticete species in this area.
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Migração Animal , Golfinhos/metabolismo , Comportamento Alimentar , Poluentes Químicos da Água/metabolismo , Baleias/metabolismo , Animais , Biomarcadores/metabolismo , Biópsia , Análise por Conglomerados , Citocromo P-450 CYP1A1/metabolismo , Fator de Transcrição E2F1/metabolismo , Hábitos , Éteres Difenil Halogenados/análise , Éteres Difenil Halogenados/metabolismo , Hidrocarbonetos Clorados/análise , Hidrocarbonetos Clorados/metabolismo , México , Bifenilos Policlorados/análise , Hidrocarbonetos Policíclicos Aromáticos/análise , Hidrocarbonetos Policíclicos Aromáticos/metabolismo , Receptores de Hidrocarboneto Arílico/metabolismo , Pele/química , Poluentes Químicos da Água/efeitos adversos , Poluentes Químicos da Água/análiseRESUMO
PURPOSE: Concurrent radio-chemotherapy (RT-CT) is the standard treatment for locally advanced head and neck squamous cell carcinoma (LA-HNSCC), but RT plus epidermal growth factor receptor (EGFR) inhibitors is an effective option when CT is not appropriate. Human papillomavirus (HPV) is associated with an improved prognosis in LA-HNSCC; however, it has not been fully studied as a prognostic factor after RT + EGFR inhibitors. EXPERIMENTAL DESIGN: Immunohistochemical expression of p16INK4A and PCR of HPV16 DNA were retrospectively analyzed in tumor blocks from 52 stage III/IV LA-HNSCC patients treated with RT + EGFR inhibitors. Disease-free survival (DFS) and overall survival (OS) were analyzed by the Kaplan-Meier method. RESULTS: DNA of HPV16 was found in six of 52 tumors (12 %) and p16 positivity in eight tumors (15 %). After a median follow-up time of 45 months (6-110), p16-positive patients treated with RT + EGFR inhibitors showed an improved DFS (2-year DFS 75 vs. 44 %, HR 0.25, 95 % CI 0.06-0.99, p = 0.047) compared with p16-negative patients. These differences were outperformed when compared by HPV16 status (2-year OS rates of 83 vs. 58 %, HR 0.17, 95 % CI 0.02-0.99, p = 0.049 and 2-year DFS rates of 83 vs. 45 %, HR 0.17, 95 % CI 0.02-0.99, p = 0.049). In the Cox regression analysis with OS as the end point, ECOG 0-1 was the only prognostic factor independently associated with a good prognosis in the multivariable analysis. CONCLUSION: In this study, p16/HPV16-positive patients with LA-HNSCC treated with RT + EGFR inhibitors showed a better survival, not confirmed in multivariate analysis.
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Carcinoma de Células Escamosas/terapia , Carcinoma de Células Escamosas/virologia , Quimiorradioterapia/métodos , Receptores ErbB/antagonistas & inibidores , Neoplasias de Cabeça e Pescoço/terapia , Neoplasias de Cabeça e Pescoço/virologia , Infecções por Papillomavirus/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/análise , Carcinoma de Células Escamosas/mortalidade , Intervalo Livre de Doença , Feminino , Neoplasias de Cabeça e Pescoço/mortalidade , Papillomavirus Humano 16/isolamento & purificação , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço , Resultado do TratamentoRESUMO
The disinfection efficiency of performic acid (PFA) against various microbial contaminants has been studied in municipal secondary effluent. The study demonstrated that PFA provides rapid, efficient and safe disinfection, degrading both bacteria and viruses even at low doses. The resistance order starting from the most resistant microorganism is as follows: MS2-coliphages > DNA-coliphages > enterococci and Escherichia coli. PFA is also efficient in the elimination of Salmonella spp., Clostridium perfringens spores and Giardia cysts. The results showed that a PFA dose as low as 0.5-1 mg L(-1) with contact time of 10 min was efficient in achieving and maintaining for 72 h the disinfection level required for unrestricted agricultural water reuse (≤3 log units for faecal coliforms). However, the optimal dose will depend on the quality of wastewater. Regarding the formation of by-products during disinfection with PFA, very low amounts of hydrogen peroxide and organic per-acids were observed; active oxygen was not detected. The amounts of adsorbable organically bound halogens (AOX) compounds formed were significantly lower compared to the amounts generated during chlorine disinfection. This chlorine-free solution enables compliance with microbiological criteria for various water reuse applications and is already on the market for advanced disinfection.
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Bactérias/efeitos dos fármacos , Bacteriófagos/efeitos dos fármacos , Desinfetantes/farmacologia , Desinfecção/métodos , Formiatos/farmacologia , Giardia/efeitos dos fármacos , Desinfetantes/análise , Finlândia , Formiatos/análise , México , Eliminação de Resíduos Líquidos/métodos , Águas Residuárias/microbiologia , Águas Residuárias/parasitologia , Águas Residuárias/virologia , Purificação da Água/métodosRESUMO
Upon oxygen shift-down, Mycobacterium tuberculosis complex bacteria can induce a genetic program characterized by halted duplication, which is called Non-replicating persistence (NRP). During this phase, at least 48 genes, collectively named Dormancy survival regulator (DosR) regulon, are important for the long-term survival of bacilli under a non-respiring state, a condition that bacilli encounter inside granulomatous lesions. It remains unclear whether expression of NRP genes occurs within the tissue of Mycobacterium bovis naturally infected cattle. In order to start dissecting this question, total RNA from bovine lymph node tissues of sacrificed tuberculin reacting animals was isolated and transcription of genes required for in vivo duplication (esxB and fbpB) and in vitro NRP (hspX, pfkB, and mb2660c) were analyzed by RT-PCR approaches. Detection of transcripts was positive in bovine tissue samples for genes hspX, pfkB, and mb2660c in 84, 32, and 21%, respectively. NRP genes were upregulated even in animals with a negative IFN-γ in vitro test, and the expression of NRP genes occurred more often than expression of the esxB gene.
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Proteínas de Bactérias/metabolismo , Regulação Bacteriana da Expressão Gênica , Linfonodos/microbiologia , Mycobacterium bovis/crescimento & desenvolvimento , Regulação para Cima , Animais , Proteínas de Bactérias/genética , Bovinos , Interferon gama/biossíntese , Testes de Liberação de Interferon-gama , Mycobacterium bovis/genética , Mycobacterium bovis/metabolismo , Mycobacterium bovis/patogenicidade , Regulon , Testes Cutâneos , Teste Tuberculínico , Tuberculose Bovina/microbiologiaRESUMO
Helminth eggs are the most difficult biological parasites to inactivate in wastewater and sludge. In developing countries, in particular, they are present in high concentrations and are the cause of many diseases that impact seriously on the human population. The process conditions for affordable inactivation are very variable, leading to different inactivation efficiencies. Temperature, dryness, pH and the developmental stage of the eggs must be taken into consideration to achieve complete inactivation. The objective of this research was to study the inactivation of six species of larval and non-larval helminth eggs of medical importance in developing countries under controlled conditions of temperature, pH, dryness and contact time. Results showed considerable differences in inactivation conditions among helminth eggs and a high level of resistance was confirmed for the eggs of Ascaris lumbricoides and Ascaris suum. The appropriate conditions for inactivation of all types of eggs were found by applying combinations of pH, temperature and dryness. At 45 °C it was possible to inactivate all species with a pH of 5.3 and 90% dryness within 6 days. If alkalization was applied, a pH of 12.7 was sufficient over 19 days at the same conditions of dryness and temperature. From these results it is proposed that both Ascaris spp. and Taenia solium may be used as indicators of biological contamination in wastewater and sludge.
Assuntos
Ovos , Helmintos/crescimento & desenvolvimento , Umidade , Concentração de Íons de Hidrogênio , Larva/fisiologia , Temperatura , Animais , Modelos TeóricosRESUMO
This study aimed to investigate the impact of contamination by persistent organic pollutants (POPs) on Brazilian wildlife. The concentrations of certain POPs, including dichlorodiphenyltrichloroethane (DDT) and polychlorinated biphenyls (PCBs), in the eggs of the brown booby (Sula leucogaster) were measured. The eggs were collected from breeding colonies located on three archipelagos (Saint Peter and Saint Paul, Abrolhos and Cagarras Islands) in the Atlantic Ocean, which are located at different distances from the Brazilian coast (range 4-1010 km). In addition, possible alterations in eggshell characteristics were evaluated. The average values of POPs found in eggs from the archipelago of Saint Peter and Saint Paul (0.05µgg(-1) of ΣPCBs and 0.01 µg g(-1) of ΣDDT) and the archipelago of Abrolhos (0.19 µg g(-1) of ΣPCBs and 0.03 µg g(-1) of ΣDDT) were low compared to the reference values reported in the literature. In contrast, the concentrations measured in eggs from Cagarras (8.4 µg g(-1) of ΣPCBs and 1.8 µg g(-1) of ΣDDT) were the highest, and this total PCB level is close to the threshold values considered to be harmful to birds. Our findings indicate that the brown booby colony closest to the Rio de Janeiro coast has recently been exposed to DDT. Despite the high pollution levels found on the Cagarras Islands, no alterations in the eggshell weight or the thickness of the analyzed eggs were detected. Hence, more detailed studies are recommended to determine the actual effects of the selected POPs on the Cagarras breeding colony.
Assuntos
Aves , Poluentes Ambientais/análise , Poluentes Ambientais/toxicidade , Óvulo/química , Animais , Oceano Atlântico , Brasil , DDT/análise , Casca de Ovo/química , Feminino , Tamanho do Órgão/efeitos dos fármacos , Bifenilos Policlorados/análiseRESUMO
AIM This study was a retrospective analysis of our experience with severe cross-hypersensitivity reactions (HSR) to the taxanes paclitaxel (P) and docetaxel (D) in patients with breast cancer. PATIENTS AND METHODS We evaluated patients with breast cancer treated with P or D who experienced severe HSR to one of the two taxanes. Severe HSR was defined as any reaction severe enough to warrant discontinuation of the drug. Initial intravenous premedication for paclitaxel was dexamethasone (20 mg), ranitidine (50 mg) and dexchlorpheniramine (10 mg). For docetaxel, dexamethasone (4 mg) orally every 12 hours was administered the day before infusion and dexamethasone (20 mg) was administered intravenously prior to infusion. After severe HSR to the taxane and 30 minutes before infusion of another taxane, we administered dexamethasone (20 mg), ranitidine (50 mg) and dexchlorpheniramine (10 mg) iv as a premedication, and we also increased the time of the infusion. RESULTS Between March 2009 and April 2010, 23 patients experienced an initial severe HSR to taxane (12 P, 11 D). Substitution of another taxane was conducted in 17 patients in the two weeks following the initial HSR. Eight patients had an initial HSR with P, and three had a cross-HSR to D. Nine patients had an initial HSR to D, and four of these patients had a cross-HSR to P. Among the 17 patients who received both taxanes, 7 (41%) had a cross-HSR. All cross- HSRs were sufficiently severe (grade 3-4) to suspend taxane treatment permanently. In the remaining 6 patients, a desensitisation protocol to taxanes was performed by increasing the dose of the diluted drug (4 P, 2 D), which resulted in administration of the drug without complications in all cases. There were no treatment-related deaths. CONCLUSION Severe cross-HSR between P and D occurred in a significant proportion of our patients with breast cancer, so care must be taken when substituting taxanes (paclitaxel and docetaxel). A desensitisation protocol can be an effective alternative to decrease the risk of a new HSR.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Hipersensibilidade a Drogas/etiologia , Adulto , Idoso , Anti-Inflamatórios/uso terapêutico , Dexametasona/uso terapêutico , Docetaxel , Hipersensibilidade a Drogas/prevenção & controle , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Paclitaxel/administração & dosagem , Pré-Medicação , Estudos Retrospectivos , Taxoides/administração & dosagem , Resultado do TratamentoRESUMO
An analysis of the actual WHO recommendations to develop standards for the safe reuse of wastewater, excreta or sludge in agriculture using a quantitative microbial risk assessment (QMRA) is presented. The proposed values are defined using a risk-based model for Ascaris lumbricoides infection to assess the human risks associated with exposure to this pathogen from crops irrigated with polluted water, or from crops grown in biosolid-enriched soil. From the results it becomes evident that, with regard to helminth eggs, the WHO guidelines for wastewater reuse in agriculture seem more stringent than are needed in developing countries, while for the reuse of sludge they appear to be the opposite. Although more information is needed to confirm this conclusion, which was derived from a single piece of research, at the very least a more cautious approach is recommended when evaluating excreta or sludge for agricultural purposes in developing countries. Additionally, this work shows that the application of some barriers, other than wastewater and sludge treatment as suggested by WHO, can play an important role in controlling risks.
Assuntos
Agricultura/métodos , Ascaris lumbricoides/isolamento & purificação , Esgotos/parasitologia , Eliminação de Resíduos Líquidos/métodos , Purificação da Água/métodos , Animais , Ascaríase/prevenção & controle , Países em Desenvolvimento , Monitoramento Ambiental , Humanos , México , Modelos Teóricos , Óvulo , Contagem de Ovos de Parasitas , Medição de Risco/normas , Eliminação de Resíduos Líquidos/normasRESUMO
Introducción. De la coagulopatía aguda en el trauma, resultan múltiples complicaciones como la necesidad de administración de hemoderivados, mayor incidencia de disfunción orgánica, aumento de estancia en unidad de cuidados intensivos y mayor mortalidad. Con el conocimiento actual de la fisiopatología del trauma y la vía celular de la coagulación es ahora posible mejorar el dignóstico y tratamiento de la coagulopatía inicial y conseguir mejores resultados en nuestros centros. Métodos. Este artículo examina la fisiología básica de la coagulación, la etiología, el diagnóstico y el tratamiento de la coagulopatía temprana en trauma. La búsqueda se realizó con términos Mesh y no Mesh con conectores AND: Anesthesia-coagulophaty, postinjury and trauma thromboelastography, transfusion and trauma, shock-Mechanism and trauma review. Resultados. La coagulopatía aguda o temprana en trauma está directamente asociada al estado de shock y se caracteriza por anticoagulación e hiperfibrinolisis sistémica; hay evidencia de la implicación de la proteína C en este proceso. Se ha establecido que seis mecanismos fisiopatológicos multifactoriales pueden perpetuar la coagulopatía en los pacientes traumatizados; éstos son: inflamación, acidosis, hipotermia, shock, trauma tisular y hemodilución. El diagnóstico se realiza con las diferentes pruebas (TP, TPT, plaquetas) ya conocidas desde hace mucho tiempo, pero con limitaciones que reducen su utilidad clínica. Ahora la tromboelastografía nos puede ayudar a guiar la transfusión, con el concepto actual de transfusión temprana de glóbulos rojos, plasma y plaquetas, utilizando la mejor proporción según la evidencia disponible. Conclusiones. Contamos, con algún conocimiento sobre la fisiopatología de la coagulopatía asociada con trauma pero son necesarias más investigaciones, en este campo. El diagnóstico rápido y una intervención directa inmediata son importantes para mejorar el desenlace de nuestros pacientes.
Introduction. Acute coagulopathy in trauma results in multiple complications such as the need for blood products, higher rates of organ dysfunction, longer stay in the ICU and higher mortality. With the current knowledge of the pathophysiology of trauma and of the cellular coagulation pathway it is now possible to improve diagnosis and treatment of the initial coagulopathy and achieve better outcomes in our trauma centers. Methods. This paper looks into the basic physiology of coagulation, and the etiology, diagnosis and treatment of early coagulopathy in trauma. The search was done using Mesh and non-Mesh terms with AND connectors: Anesthesia-coagulopathy, postinjury and trauma thromboelastography, transfusion and trauma, shock-Mechanism and trauma review. Results. Acute or early coagulopathy in trauma is directly associated with a state of shock and is characterized by anticoagulation and systemic hyperfibrinolysis; protein C is known to be implicated in this process. It has also been determined that six multi-factorial pathophysiological mechanisms may perpetuate coagulopathy in trauma patients, namely, inflammation, acidosis, hypothermia, shock, tissue trauma and hemodilution. Diagnosis is made using the different tests (PT, PPT, platelets) that have been in use for a long time; however, these tests have drawbacks that limit their clinical usefulness. Thromboelastography can now help guide early transfusion using the best proportion of red blood cells, plasma and platelets on the basis of the best available evidence. Conclusions. We have some knowledge about the pathophysiology coagulopathy associated with trauma but more research in this field is needed. Rapid diagnosis and immediate intervention are important to improve the outcomes with our patients.