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BACKGROUND: Cardiovascular disease (CVD) is one of the main causes of death and disability worldwide. The etiology of CVD is often associated with multiple risk factors, with environmental factors receiving considerable attention. Individuals with precarious jobs are among the groups most affected by chronic exposure to environmental pollutants. AIM: This study aimed to evaluate occupational exposure to heavy metals among individuals in precarious job settings and investigate atherogenic indices as biomarkers of cardiovascular risk. METHODS: A total of 137 workers participated in this cross-sectional study conducted in three work environments in San Luis Potosi, Mexico. Urine and blood samples were collected to assess metal exposure and biochemical profiles, including atherogenic indices. RESULTS: The results showed that workers in the brick sector exhibited the highest levels of metal exposure, particularly arsenic (44.06 µg/L), followed by stonecutters and garbage collectors (24.7 and 16.9 µg/L, respectively). Similarly, Castelli risk index (CRI) and the atherogenic index of plasma (AIP) were higher in brickmakers (3.883 and 0.499) compared to stonecutters (3.285 and 0.386) and garbage collectors (3.329 and 0.367). CONCLUSIONS: Evidence of exposure to heavy metals was observed in the three populations, in addition to the fact that individuals with greater exposure to arsenic also exhibited higher CRI and AIP.
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Arsênio , Aterosclerose , Doenças Cardiovasculares , Metais Pesados , Humanos , Arsênio/toxicidade , Arsênio/urina , México/epidemiologia , Estudos Transversais , Metais Pesados/análise , Metais Pesados/urina , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , BiomarcadoresRESUMO
The aim of the study was to evaluate renal function in three groups of precarious workers: garbage recyclers (REC), quarry workers (CAN), and brick makers (LAD). Samples of urine and blood were collected to evaluate clinical parameters and the metal levels in urine was measured using ICP-MS. REC group had the highest concentrations of chromium in urine (36.03 ± 27.2 µg/l) compared to CAN and LAD groups. Mercury concentrations were higher in the LAD group (3.7 ± 0.8 µg/l). Additionally, arsenic was detected in both CAN and REC groups (25.4 ± 26.2 and 19.09 ± 16.7 µg/l, respectively), while arsenic concentrations in LAD were higher (47.2 ± 30.8 µg/l). In kidney biomarkers, ß2-microglobulin concentrations were higher in the REC group (87867 ± 115159.5 ng/g UCr). Similarly, cystatin-C concentrations were higher in the REC group (32795.61 ± 34965.8 ng/g UCr). The data suggests that precarious workers are exposed to heavy metals and have elevated protein levels that contribute to kidney damage.
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Arsênio , Mercúrio , Metais Pesados , Humanos , Arsênio/análise , México , Metais Pesados/toxicidade , Metais Pesados/análise , Mercúrio/toxicidade , Rim/químicaRESUMO
The Kosakonia cowanii Cp1 strain was isolated from seeds of Capsicum pubescens R. & P. cultivated in Michoacan, Mexico. Genetic and ecological role analyses were conducted for better characterization. The results show that genome has a length of 4.7 Mbp with 56.22% G + C and an IncF plasmid of 128 Kbp with 52.51% G + C. Furthermore, pathogenicity test revealed nonpathogenic traits confirmed by the absence of specific virulence-related genes. Interestingly, when fungal inhibitory essays were carried out, the bacterial synthesis of volatile organic compounds (VOCs) with antifungal activity showed that Sclerotinia sp. and Rhizoctonia solani were inhibited by 87.45% and 77.24%, respectively. Meanwhile, Sclerotium rolfsii, Alternaria alternata, and Colletotrichum gloeosporioides demonstrated a mean radial growth inhibition of 52.79%, 40.82%, and 55.40%, respectively. The lowest inhibition was by Fusarium oxysporum, with 10.64%. The VOCs' characterization by headspace solid-phase microextraction combined with gas chromatography-mass spectrometry (HS-SPME-GC-MS) revealed 65 potential compounds. Some of the compounds identified with high relative abundance were ketones (22.47%), represented by 2-butanone, 3-hydroxy (13.52%), and alcohols (23.5%), represented by ethanol (5.56%) and 1-butanol-3-methyl (4.83%). Our findings revealed, for the first time, that K. cowanii Cp1 associated with C. pubescens seeds possesses potential traits indicating that it could serve as an effective biocontrol.
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The marine microturbellarian diversity is scarcely known from the Pacific coastline of South America. The coastal margin of Peru is highly influenced by cold-water currents (Humboldt Current System). These cold-water currents play important roles in shaping the marine species diversity in this area. However, there are no previous records of marine microturbellarians for Peru. Here, we describe a new species of Rhabdocoela and report on five other species of marine microturbellarians for this country. Carcharodorhynchus giaae n. sp. (Kalyptorhynchia, Schizorhynchidae), can be identified based on the configuration of the proboscis lips and the male and female genital systems. The male copulatory organ lacks a cirrus, but has a funnel-like, curved stylet with three pairs of spines along it, which distinguishes this species from its congeners. The female system has a vagina with a sclerotized, heavily coiled structure - a feature not mentioned in any known species of the same genus. In addition, we describe noteworthy features for another rhabdocoel, Trigonostomum galapagoense (Dalytyphloplanida, Trigonostomidae). Finally, we provide new records for three rhabdocoel species (Alcha evelinae, Itaipusa divae, Utelga heinckei), one species of Fecampiida (Urastoma cyprinae), and an unidentified species of Prolecithophora.
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Besouros , Platelmintos , Animais , Masculino , Feminino , PeruRESUMO
Triple negative breast cancer (TNBC) is the breast cancer subtype with the worst prognosis and still lacks a targeted therapy. In this study, we found increased ERK phosphorylation in TNBC cell lines and an important role for ERK in sustaining the migration of TNBC cells. Although ROS have been suggested to have an important role in sustaining MAPK signaling, antioxidant treatment increased ERK phosphorylation, probably suggesting increased invasive potential. Interestingly, treatment with PD0325901 (PD), a MEK inhibitor, decreased ROS levels in TNBC cells and decreased mitochondrial fragmentation in the MDAMB231 cell line. Our data supports an important role for MEK/ERK in TNBC, sustaining cellular migration, regulating mitochondrial dynamics and ROS production in this breast cancer subtype.
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Neoplasias de Mama Triplo Negativas , Humanos , Neoplasias de Mama Triplo Negativas/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Quinases de Proteína Quinase Ativadas por Mitógeno , Proliferação de CélulasRESUMO
El 90% de los niños sordos nacen en hogares de padres oyentes y pueden experimentar retrasos en la adquisición del lenguaje debido a la falta de exposición temprana a la lengua de señas. La Evaluación Neuropsicológica Infantil 2 (ENI-2) puede ser utilizada para evaluar las habilidades lingüísticas y cognitivas de niños y jóvenes, para lo cual dispone de algunas tareas que es necesario adaptar para ser aplicada en el caso de las personas Sordas. Esta investigación de enfoque cuantitativo, alcance descriptivo y tipo transversal consta de una adaptación inicial a la prueba ENI-2 y su respectivo pilotaje, con el fin de brindar una herramienta y datos preliminares, que pueden contribuir a generar una caracterización cognitiva y lingüística de niños y jóvenes Sordos. La adaptación realizada implicó aspectos como seleccionar las pruebas, modificar la modalidad de la respuesta de algunas tareas, postular un equivalente acorde al contexto bilingüe de las personas Sordas, ajustar estímulos e indicaciones, interpretar en lengua de señas colombiana las indicaciones, entre otras. Se debe tener en cuenta que este es solo un primer acercamiento al proceso de adaptación de la prueba, dado que se evidenció luego del pilotaje la necesidad de realizar más ajustes. Se contó con una muestra a conveniencia no probabilística, con la participación de 7 estudiantes (5 hombres y 2 mujeres) de un colegio para Sordos en la ciudad de Bogotá. Además de aportar la propuesta inicial de adaptación, los resultados de este estudio serán útiles para postular un perfil inicial de habilidades lingüísticas y cognitivas de jóvenes sordos, lo que puede facilitar el enfocar acciones de intervención fonoaudiológica, en torno a las habilidades de los escolares Sordos inmersos en un modelo educativo bilingüe-bicultural.
90% of deaf children are born into hearing parents' households and may experience delays in language acquisition due to a lack Neuropsychological Assessment 2 (INAP-2) can be used to assess the linguistic and cognitive abilities of children and youth, for which some tasks need to be adapted for application in the case of Deaf individuals. This quantitative research with a descriptive scope and cross-sectional design consists of an initial adaptation of the INAP-2 test and its respective pilot study, in order to provide a tool and preliminary data that can contribute to generating a cognitive and linguistic characterization of Deaf children and youth. The adaptation process involved aspects such as selecting the tests, modifying the response mode for some tasks, proposing an equivalent suitable for the bilingual context of Deaf individuals, adjusting stimuli and instructions, interpreting instructions in Colombian Sign Language, among others. It should be noted that this is just an initial approach to the test adaptation process, as further adjustments were identified after the pilot study. A non-probabilistic convenience sample was used, involving the participation of 7 students (5 males and 2 females) from a school for the Deaf in the city of Bogotá. In addition to providing the initial adaptation proposal, the results of this study will be useful for establishing an initial profile of linguistic and cognitive skills in Deaf youth, which can facilitate the focus of speech therapy intervention actions regarding the skills of Deaf students immersed in a bilingual-bicultural educational model.
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AIM: Evaluate the expression of exomiRs-126, -146, and -155 in urinary exosomes of patients with T2DM and diabetic kidney disease to establish a predictive classification model with exomiRs and clinical variables in order to determine their contribution to DKD. METHODS: The study group included 92 subjects: 64 patients diagnosed with T2DM subclassified into two groups with albuminuria (T2DM with albuminuria, n = 30) and without albuminuria (TD2M, n = 34) as well as 28 healthy, non-diabetic participants. Exosomes were isolated from urine and identified by TEM and flow cytometry. Profile expression of exomiRs-126, -146 and -155 was evaluated by RT-qPCR. Data were analysed by permutational multivariate analysis of variance (PERMANOVA), similarity percentage (SIMPER), principal coordinate analysis (PCO), and canonical analysis of principal coordinates (CAP). RESULTS: T2DM patients with and without albuminuria showed higher levels of miR-155 and miR-146 compared with controls. In addition, T2DM patients with albuminuria presented a significant increase in miR-126 contrasted to controls and patients without albuminuria. PCO analysis explained 34.6% of the total variability of the data (PERMANOVA; p < .0001). Subsequently, SIMPER analysis showed that miR-146, miR-155, and miR-126 together, with some clinical parameters, contributed to 50% of the between-group significance. Finally, the CAP analysis developed showed a correct classification of 89.01% with the analysed parameters. CONCLUSION: A platform using a combination of clinical variables and exomiRs could be used to classify individuals with T2D as risk for developing DKD.
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Diabetes Mellitus Tipo 2 , Nefropatias Diabéticas , MicroRNAs , Albuminúria/etiologia , Albuminúria/genética , Biomarcadores , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/genética , Nefropatias Diabéticas/etiologia , Nefropatias Diabéticas/genética , Feminino , Humanos , Masculino , MicroRNAs/genética , MicroRNAs/metabolismoRESUMO
RESUMEN Fundamento: las intoxicaciones agudas en niños constituyen una emergencia médica grave y son consideradas un problema de salud pública creciente a nivel mundial. Objetivo: caracterizar las intoxicaciones agudas en pacientes con ingreso en hospital pediátrico de la provincia Sancti Spíritus en el período 2014-2018. Métodos: se realizó un estudio descriptivo de corte transversal en el período 2014-2018. La información se obtuvo a través de la revisión de todas las historias clínicas de los pacientes ingresados. Se analizaron las variables edad, sexo, tipo de intoxicación circunstancial ya sea intencional o no, lugar de ocurrencia, vías de exposición, estadía hospitalaria y agente responsable. Se calcularon frecuencias absolutas y relativas. Resultados: predominaron las intoxicaciones accidentales sobre las voluntarias, ambas con tendencia al aumento. Las niñas presentaron el mayor porcentaje, por causa intencional a partir de los 11 años; los varones prevalecieron en el rango de 1 a 5 años por causa accidental. Los medicamentos (66,7 %) fueron los agentes causales más involucrados en ambos tipos de intoxicaciones, la vía digestiva fue la más frecuentemente observada, representativa de un 95,6 %. El 80,6 % de los casos ocurrió en el hogar y presentaron una estadía hospitalaria corta, con tres días o menos en la mayoría de ellas. Conclusiones: las intoxicaciones exógenas en niños son causa de morbilidad en la provincia de Sancti Spíritus, por lo que es de vital importancia dar seguimiento a los resultados obtenidos en esta investigación, tales como el índice de intoxicación por psicofármacos.
ABSTRACT Background: acute poisoning in children is a serious medical emergency and is considered a growing public health problem worldwide. Objective: to characterize acute intoxications in patients admitted to a pediatric hospital in Sancti Spíritus province from 2014 to 2018. Methods: a descriptive cross-sectional study was carried out from 2014 to 2018. The information was obtained through the review of all the medical records of the admitted patients. The variables age, sex, type of circumstantial poisoning, whether intentional or not, place of occurrence; routes of exposure, hospital stay and responsible agent were analyzed. Absolute and relative frequencies were calculated. Results: accidental poisonings prevailed over voluntary poisonings, both with a tendency to increase. Girls presented the highest percentage, due to intentional causes from 11 years old; boys prevailed in the range of 1 to 5 years due to accidental causes. Medications (66.7%) were the causal agents most involved in both types of poisoning, the digestive tract was the most frequently observed, representing 95.6%. 80.6% of the cases occurred at home and presented a short hospital stay, with three days or less in most of them. Conclusions: exogenous intoxications in children are a cause of morbidity in the Sancti Spíritus province, so it is vitally important to follow up on the results obtained in this research, such as the rate of intoxication by psychotropic drugs.
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RESUMEN Introducción: las caries dentales y las maloclusiones son preocupaciones para pacientes y profesionales de la estomatología por su incidencia a nivel mundial, por las manifestaciones bucales que desencadenan y por la alteración estética del paciente. Objetivo: identificar la incidencia de caries, maloclusión y caries-maloclusión en adolescentes de 7mo grado de la Escuela Secundaria Básica "XXX Aniversario de la Batalla de Guisa" del municipio Bayamo. Métodos: se realizó una investigación descriptiva transversal en los adolescentes de 7mo grado en el período de enero de 2017 a diciembre de 2018 con un universo de 142 estudiantes. Resultados: se reveló que el sexo masculino tuvo una incidencia de 85,71% de afectación por caries dental, la maloclusión incidió en el 43,10 % en el sexo femenino; la incidencia de caries-maloclusión en la población objeto de estudio, fue de 29,31 % y 27,38 % según el sexo femenino y masculino respectivamente. Conclusiones: se determinó la incidencia de la caries dental, maloclusiones y caries-maloclusión las cuales tuvieron una alta incidencia en la población adolescente.
ABSTRACT Introduction: dental caries and malocclusions are concerns for patients and dental professionals due to their worldwide incidence, due to the oral manifestations that they trigger and due to the aesthetic alteration of the patient. Objective: to identify the incidence of caries, malocclusion and caries-malocclusion in 7th grade adolescents from the Basic Secondary School "XXX Anniversary of the Battle of Guisa" of the Bayamo municipality. Methods: a cross-sectional descriptive research was carried out in the 7th grade adolescents in the period from January 2017 to December 2018 with a universe of 142 students. Results: it was revealed that the male sex had an incidence of 85.71% of affectation by dental caries, the malocclusion affected 43.10% in the female sex; the incidence of caries-malocclusion in the population under study was 29.31% and 27.38% according to the female and male sex, respectively. Conclusions: the incidence of dental caries, malocclusions and caries-malocclusion was determined, which had a high incidence in the adolescent population.
RESUMO Introdução: a cárie e as maloclusões são uma preocupação dos pacientes e profissionais da odontologia devido à sua incidência mundial, pelas manifestações bucais que desencadeiam e pela alteração estética do paciente. Objetivo: identificar a incidência de cárie, má oclusão e má oclusão cárie em adolescentes da 7ª série do Ensino Médio Básico "XXX Aniversário da Batalha de Guisa" do município de Bayamo. Métodos: foi realizada uma pesquisa descritiva transversal realizada com adolescentes da 7ª série no período de janeiro de 2017 a dezembro de 2018 com um universo de 142 alunos. Resultados: revelou-se que o sexo masculino teve uma incidência de 85,71% de acometimento por cárie dentária, a má oclusão afetou 43,10% no sexo feminino; a incidência de maloclusão cárie na população em estudo foi de 29,31% e 27,38% de acordo com o sexo feminino e masculino, respectivamente. Conclusões: foi determinada a incidência de cárie dentária, maloclusões e má oclusão cárie, as quais tiveram alta incidência na população de adolescentes.
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Mercury mining is one of the main sources of mercury (Hg) release into the environment, causing serious impacts on human health and the environment. Workers in these mines are employed informally and precariously and therefore lack labor rights such as social security. The objective of the study is to make visible the exposure to environmental contaminants and the health of workers in mercury mines. An environmental assessment was conducted to determine workers' exposure to contaminants; urine samples were obtained to measure exposure to mercury and arsenic, and blood samples were obtained for lead and cadmium. Clinical parameters were also evaluated. Concentrations of Hg, As and Pb were determined in soil, 279.4 mg/kg (24.4-788.5), 14.7 mg/kg (9.5-20.3) and 1.4 mg/kg (1-2.8), respectively. The exposure results for mercury were 551 µg/g creatinine, for arsenic 50 µg/L and for lead 4.7 µg/dL. Cd-B was not found. In addition, 17.6 % of the workers had diabetes and 17.6 % had renal disorders. Principal Component Regression was performed obtaining an r2 of 0.86 for glomerular filtration rate and 0.54 for albumin creatinine ratio using clinical, occupational, and metal exposure variables. Exposure to Hg in this type of mine is not exclusive, so there is a cumulative risk of chronic exposure to different environmental pollutants directly impacting the health of workers. It is necessary to implement health strategies and different work opportunities for these workers.
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Arsênio , Mercúrio , Humanos , Mercúrio/análise , Exposição Ambiental/análise , Arsênio/análise , Monitoramento Ambiental , Creatinina , Mineração , EmpregoRESUMO
Cryo-electron microscopy (cryo-EM) extracts single-particle density projections of individual biomolecules. Although cryo-EM is widely used for 3D reconstruction, due to its single-particle nature it has the potential to provide information about a biomolecule's conformational variability and underlying free-energy landscape. However, treating cryo-EM as a single-molecule technique is challenging because of the low signal-to-noise ratio (SNR) in individual particles. In this work, we propose the cryo-BIFE method (cryo-EM Bayesian Inference of Free-Energy profiles), which uses a path collective variable to extract free-energy profiles and their uncertainties from cryo-EM images. We test the framework on several synthetic systems where the imaging parameters and conditions were controlled. We found that for realistic cryo-EM environments and relevant biomolecular systems, it is possible to recover the underlying free energy, with the pose accuracy and SNR as crucial determinants. We then use the method to study the conformational transitions of a calcium-activated channel with real cryo-EM particles. Interestingly, we recover not only the most probable conformation (used to generate a high-resolution reconstruction of the calcium-bound state) but also a metastable state that corresponds to the calcium-unbound conformation. As expected for turnover transitions within the same sample, the activation barriers are on the order of [Formula: see text]. We expect our tool for extracting free-energy profiles from cryo-EM images to enable more complete characterization of the thermodynamic ensemble of biomolecules.
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RESUMEN Introducción: el miedo y la ansiedad son prácticamente indistinguibles, estos surgen fácilmente en la consulta estomatológica. Objetivo: determinar en los pacientes con odontofobia su posible correlación con la salud bucal general y la enfermedad periodontal en pacientes de20 a 50 años ingresados en el Servicio de Atención Primaria de la Clínica Estomatológica de Bayamo en Febrero de 2017. Métodos: se realizó una investigación epidemiológica observacional analítica transversal, el universo de 132 pacientes, todos formaron parte del estudio. La presencia de odontofobia se identificó con el apoyo de la Escala de la Ansiedad de Norman Corah y un cuestionario donde fueron estudiadas las variables: salud bucal general, enfermedad periodontal y su severidad. Fueron determinadas las frecuencias, medias, prueba de confiabilidad estadística y Odds Ratio. Resultados: el 100% de los pacientes odontofóbicos carecía de salud bucal, (OR=19.15) lo que indica la asociación entre estas dos variables. De igual manera se apreció una alta morbilidad (96.43%) y severidad de la enfermedad periodontal en pacientes con odontofobia ante el predominio y causalidad con la periodontitis crónica (OR=4.13). Conclusiones: se demostró que la odontofobia tenía asociación causal con la salud bucal general y la morbilidad y severidad de la enfermedad periodontal.
ABSTRACT Introduction: fear and anxiety are practically indistinguishable; they easily arise in the dental office. Objective: to determine in patients with odontophobia its possible correlation with general oral health and periodontal disease in patients aged 20 to 50 years admitted to the Primary Care Service of the Bayamo Stomatological Clinic in February 2017. Methods: a Cross-sectional analytical observational epidemiological research, the universe of 132 patients, all were part of the study. The presence of odontophobia was identified with the support of the Norman Corah Anxiety Scale and a questionnaire where the variables were studied: general oral health, periodontal disease and its severity. The frequencies, means, statistical reliability test and Odds Ratio were determined. Results: 100% of the odontophobic patients lacked oral health, (OR = 19.15) which indicates the association between these two variables. Similarly, a high morbidity (96.43%) and severity of periodontal disease were observed in patients with odontophobia, given the prevalence and causality with chronic periodontitis (OR = 4.13). Conclusions: odontophobia was shown to have a causal association with general oral health and the morbidity and severity of periodontal disease.
RESUMO Introdução: O medo e a ansiedade são praticamente indistinguíveis, estes surgem facilmente em consultas estomáticas. Objetivo: determinar em pacientes com odontologia sua possível correlação com a saúde bucal geral e doença periodontal em pacientes de 20 a 50 anos de idade internados no Serviço de Atenção Básica da Clínica Stomatológica Bayamo em fevereiro de 2017. Métodos: foi realizada pesquisa epidemiológica observacional transversal, universo de 132 pacientes, todos parte do estudo. A presença de odontologia foi identificada com o apoio da Escala de Ansiedade de Norman Corah e um questionário onde foram estudadas as variáveis: saúde bucal geral, doença periodontal e sua gravidade. Foram determinadas as frequências, médias, teste de confiabilidade estatística e Odds Ratio. Resultados: 100% dos pacientes odontológicos não tinham saúde bucal, (OR-19,15) indicando a associação entre essas duas variáveis. A alta morbidade também foi apreciada (96,43%) e gravidade da doença periodontal em pacientes com odontofobia em face da predominância e causalidade com periodontite crônica (OR-4.13). Conclusões: A odontologia mostrou-se uma associação causal com a saúde bucal geral e a morbidade e gravidade da doença periodontal.
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New treatments for diseases caused by antimicrobial-resistant microorganisms can be developed by identifying unexplored therapeutic targets and by designing efficient drug screening protocols. In this study, we have screened a library of compounds to find ligands for the flavin-adenine dinucleotide synthase (FADS) -a potential target for drug design against tuberculosis and pneumonia- by implementing a new and efficient virtual screening protocol. The protocol has been developed for the in silico search of ligands of unexplored therapeutic targets, for which limited information about ligands or ligand-receptor structures is available. It implements an integrative funnel-like strategy with filtering layers that increase in computational accuracy. The protocol starts with a pharmacophore-based virtual screening strategy that uses ligand-free receptor conformations from molecular dynamics (MD) simulations. Then, it performs a molecular docking stage using several docking programs and an exponential consensus ranking strategy. The last filter, samples the conformations of compounds bound to the target using MD simulations. The MD conformations are scored using several traditional scoring functions in combination with a newly-proposed score that takes into account the fluctuations of the molecule with a Morse-based potential. The protocol was optimized and validated using a compound library with known ligands of the Corynebacterium ammoniagenes FADS. Then, it was used to find new FADS ligands from a compound library of 14,000 molecules. A small set of 17 in silico filtered molecules were tested experimentally. We identified five inhibitors of the activity of the flavin adenylyl transferase module of the FADS, and some of them were able to inhibit growth of three bacterial species: C. ammoniagenes, Mycobacterium tuberculosis, and Streptococcus pneumoniae, where the last two are human pathogens. Overall, the results show that the integrative VS protocol is a cost-effective solution for the discovery of ligands of unexplored therapeutic targets.
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Antibacterianos , Proteínas de Bactérias , Nucleotidiltransferases , Antibacterianos/química , Antibacterianos/farmacologia , Proteínas de Bactérias/antagonistas & inibidores , Proteínas de Bactérias/química , Proteínas de Bactérias/metabolismo , Corynebacterium/efeitos dos fármacos , Corynebacterium/enzimologia , Desenho de Fármacos , Farmacorresistência Bacteriana/efeitos dos fármacos , Ligantes , Simulação de Dinâmica Molecular , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/enzimologia , Nucleotidiltransferases/antagonistas & inibidores , Nucleotidiltransferases/química , Nucleotidiltransferases/metabolismoRESUMO
Metabolomics is a potential tool for the discovery of new biomarkers in the early diagnosis of diseases. An ultra-fast gas chromatography system equipped to an electronic nose detector (FGC eNose) was used to identify the metabolomic profile of Volatile Organic Compounds (VOCs) in type 2 diabetes (T2D) urine from Mexican population. A cross-sectional, comparative, and clinical study with translational approach was performed. We recruited twenty T2D patients and twenty-one healthy subjects. Urine samples were taken and analyzed by FGC eNose. Eighty-eight compounds were identified through Kovats's indexes. A natural variation of 30% between the metabolites, expressed by study groups, was observed in Principal Component 1 and 2 with a significant difference (p < 0.001). The model, performed through a Canonical Analysis of Principal coordinated (CAP), allowed a correct classification of 84.6% between healthy and T2D patients, with a 15.4% error. The metabolites 2-propenal, 2-propanol, butane- 2,3-dione and 2-methylpropanal, were increased in patients with T2D, and they were strongly correlated with discrimination between clinically healthy people and T2D patients. This study identified metabolites in urine through FGC eNose that can be used as biomarkers in the identification of T2D patients. However, more studies are needed for its implementation in clinical practice.
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Cromatografia Gasosa/métodos , Diabetes Mellitus Tipo 2/metabolismo , Nariz Eletrônico , Metabolômica/métodos , Compostos Orgânicos Voláteis/urina , Adulto , Idoso , Biomarcadores/urina , Estudos Transversais , Humanos , Pessoa de Meia-Idade , Projetos PilotoRESUMO
Computer-aided strategies are useful for reducing the costs and increasing the success-rate in drug discovery. Among these strategies, methods based on pharmacophores (an ensemble of electronic and steric features representing the target active site) are efficient to implement over large compound libraries. However, traditional pharmacophore-based methods require knowledge of active compounds or ligand-receptor structures, and only few ones account for target flexibility. Here, we developed a pharmacophore-based virtual screening protocol, Flexi-pharma, that overcomes these limitations. The protocol uses molecular dynamics (MD) simulations to explore receptor flexibility, and performs a pharmacophore-based virtual screening over a set of MD conformations without requiring prior knowledge about known ligands or ligand-receptor structures for building the pharmacophores. The results from the different receptor conformations are combined using a "voting" approach, where a vote is given to each molecule that matches at least one pharmacophore from each MD conformation. Contrarily to other approaches that reduce the pharmacophore ensemble to some representative models and score according to the matching models or molecule conformers, the Flexi-pharma approach takes directly into account the receptor flexibility by scoring in regards to the receptor conformations. We tested the method over twenty systems, finding an enrichment of the dataset for 19 of them. Flexi-pharma is computationally efficient allowing for the screening of thousands of compounds in minutes on a single CPU core. Moreover, the ranking of molecules by vote is a general strategy that can be applied with any pharmacophore-filtering program.
Assuntos
Descoberta de Drogas/métodos , Avaliação Pré-Clínica de Medicamentos , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Preparações Farmacêuticas/análise , Preparações Farmacêuticas/química , Humanos , Ligantes , Modelos Moleculares , Preparações Farmacêuticas/metabolismo , Ligação ProteicaRESUMO
Resumen: El hígado graso agudo del embarazo es una de las alteraciones hepáticas con mayor mortalidad (cerca del 18%) presentes en la gestación, aunque es una patología poco frecuente: 1 de cada 7000 a 16.000 embarazos presenta muchas complicaciones y requiere un manejo inmediato para evitar la muerte de la gestante o del feto; sin embargo esta patología se puede enmascarar con la preeclampsia, que es otra patología hepática de mayor frecuencia, lo cual retrasa el manejo y aumenta el número de complicaciones. El objetivo de este artículo es realizar una búsqueda bibliográfica acerca del hígado graso agudo del embarazo e identificar los factores similares entre esta patología y la preeclampsia severa para lograr hacer un diagnóstico y manejo oportunos. Para ello se realizó una búsqueda sistemática en las bases de datos, PubMed, Science Direct, Medline, Embase, en junio de 2017; además, se seleccionaron artículos originales, reportes de casos y artículos de revisión, publicados en los últimos diez años.
Abstract: Acute fatty liver of pregnancy (AFLP) is one of the liver disorders with the highest mortality rate (about 18%) during pregnancy, although it is rare: 1 in 7,000 to 16,000 pregnancies has many complications and requires immediate treatment to avoid the death of the pregnant woman or the fetus. However, this pathology can be masked by preeclampsia, which is another more frequent liver disease. This delays treatment and increases the number of complications. The aim of this article is to conduct a bibliographic search about AFLP and identify similar factors between this pathology and severe preeclampsia to make a diagnosis and provide treatment in a timely manner. For this, a systematic search was carried out in databases (PubMed, Science Direct, Medline, Embase) in June 2017. In addition, original articles, case reports, and review articles published in the last ten years were selected.
Resumo: O fígado gorduroso agudo da gestação é uma das alterações hepáticas com mais mortalidade (cerca de 18 %) presentes na gravidez, embora seja uma patologia pouco frequente: 1 de cada 7.000 a 16.000 gestações apresenta muitas complicações e requer uma ação imediata para evitar a morte da gestante ou do feto. Contudo, essa patologia pode ser camuflada com a pré-eclâmpsia, que é outra patologia hepática de maior frequência, o que atrasa seu tratamento e aumenta o número de complicações. Nesse sentido, o objetivo deste estudo é realizar uma busca bibliográfica sobre o fígado gorduroso agudo da gestação e identificar os fatores semelhantes entre ele e a pré-eclâmpsia grave para poder fazer um diagnóstico e tratamento oportunos. Para isso, foi realizada uma busca sistemática nas bases de dados, PubMed, Science Direct, Medline, Embase, em junho de 2017, das quais foram selecionados artigos originais, relatos de caso e artigos de revisão, publicados nos últimos dez anos.
Assuntos
Humanos , Feminino , Gravidez , Fígado Gorduroso/patologia , Pré-Eclâmpsia , Complicações na Gravidez , DiagnósticoRESUMO
RESUMEN Introducción: la visita al estomatólogo es una es una de las atenciones en salud que más ansiedad genera en las personas, estas pueden, llegar hasta el miedo y la fobia. Objetivo: determinar la posible asociación entre la odontofobia y la salud dental en pacientes de 20 a 50 años ingresados en el Servicio de Atención Primaria de la Clínica Estomatológica de Bayamo en febrero de 2017. Método: se realizó investigación epidemiológica observacional analítica transversal, el universo de 132 pacientes, todos formaron parte del estudio. La presencia de odontofobia se identificó con el apoyo de la Escala de la Ansiedad de Norman Corah y un cuestionario donde fueron estudiadas las variables: estado clínico de los dientes afectados y pérdida dentaria, luego se determinaron por cientos, medias, prueba de confiabilidad estadística y Odds Ratio. Resultados: predominaron los pacientes odontofóbicos con dientes clínicamente afectados por diversas causas (media=16,14), existió asociación estadística entre odontofobia y dientes afectados (OR=1.38) a expensas fundamentalmente de los dientes con indicaciones de extratacción (OR=1.94). Esta situación contribuyo en gran medida a la alta pérdida dentaria (53,57% - OR=4.38). Conclusiones: se demostró la asociación causal entre odontofobia y salud dental, determinada por estado clínico de los dientes afectados y la pérdida dentaria.
ABSTRACT Introduction: the visit to the stomatologist is one of the health care that generates more anxiety in people; they can reach fear and phobia. Objective: to determine the possible association between odontophobia and dental health in patients aged 20 to 50 years admitted to the Primary Care Service of the Stomatology Clinic of Bayamo in February 2017. Method: transversal analytical observational epidemiological research was carried out, the universe of 132 patients; all of them were part of the study. The presence of odontophobia was identified with the support of the Norman Corah Anxiety Scale and a questionnaire where variables were studied: clinical status of affected teeth and tooth loss, then were determined by hundreds, means, statistical reliability test and Odds Ratio. Results: predominantly odontophobic patients with teeth clinically affected by various causes (mean = 16.14), there was a statistical association between odontophobia and affected teeth (OR = 1.38), mainly at the expense of the patients with indications of extension (OR = 1.94). This situation contributed to a large extent to the high dental loss (53.57% - OR = 4.38). Conclusions: the causal association between odontophobia and dental health was demonstrated, determined by the clinical state of the affected teeth and tooth loss.
RESUMO
Consensus-scoring methods are commonly used with molecular docking in virtual screening campaigns to filter potential ligands for a protein target. Traditional consensus methods combine results from different docking programs by averaging the score or rank of each molecule obtained from individual programs. Unfortunately, these methods fail if one of the docking programs has poor performance, which is likely to occur due to training-set dependencies and scoring-function parameterization. In this work, we introduce a novel consensus method that overcomes these limitations. We combine the results from individual docking programs using a sum of exponential distributions as a function of the molecule rank for each program. We test the method over several benchmark systems using individual and ensembles of target structures from diverse protein families with challenging decoy/ligand datasets. The results demonstrate that the novel method outperforms the best traditional consensus strategies over a wide range of systems. Moreover, because the novel method is based on the rank rather than the score, it is independent of the score units, scales and offsets, which can hinder the combination of results from different structures or programs. Our method is simple and robust, providing a theoretical basis not only for molecular docking but also for any consensus strategy in general.
RESUMO
RESUMEN La telangiectasia hemorrágica hereditaria es una enfermedad genética rara, perteneciente al grupo de púrpuras angiopáticas de tipo congénito, caracterizada por lesiones vasculares, encontrando frecuentemente telangiectasias en piel y mucosa del tracto gastrointestinal, fístulas arteriovenosas pulmonares y malformaciones vasculares en sistema nervioso central. Su manifestación clínica más frecuente son las hemorragias del tracto respiratorio superior. Este es el caso de una adolescente de 13 años con hallazgos de hepatopatía crónica, esplenomegalia difusa, pancitopenia, fístulas arteriovenosas pulmonares, deterioro neurológico progresivo secundario a hemorragia subaracnoidea con posterior defunción. Se realizó autopsia médicocientífica que reveló múltiples telangiectasias en mucosas, cirrosis de Osler, malformaciones arteriovenosas en polígono encefálico, hemorragia intraventricular con extensión subaracnoidea y bronconeumonía bibasal con pleuritis secundaria.
ABSTRACT Hereditary hemorrhagic telangiectasia is a rare genetic disease, belonging to the group of congenital angiopathic purpuras. Vascular injuries characterize it, being the most frequent telangiectasia on the skin and the gastrointestinal tract mucosa, pulmonary arteriovenous fistulas and vascular malformations in the central nervous system. The most frequent clinical manifestations are hemorrhages from the upper respiratory tract. It is presented the case of a 13-year-old girl with findings of chronic liver disease, diffuse splenomegaly, pancytopenia, pulmonary arteriovenous fistulas, progressive neurological deterioration secondary to subarachnoid hemorrhage with subsequent death. A medical-scientific autopsy was carried out that revealed multiple telangiectasias in mucous membranes, Osler's cirrhosis, arteriovenous malformations in the brain polygon, intraventricular hemorrhage with subarachnoid extension, and bibasal bronchopneumonia with secondary pleuritis.