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1.
Infect Immun ; 92(6): e0001624, 2024 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-38771050

RESUMEN

Polymyxin resistance in carbapenem-resistant Klebsiella pneumoniae bacteria is associated with high morbidity and mortality in vulnerable populations throughout the world. Ineffective antimicrobial activity by these last resort therapeutics can occur by transfer of mcr-1, a plasmid-mediated resistance gene, causing modification of the lipid A portion of lipopolysaccharide (LPS) and disruption of the interactions between polymyxins and lipid A. Whether this modification alters the innate host immune response or carries a high fitness cost in the bacteria is not well established. To investigate this, we studied infection with K. pneumoniae (KP) ATCC 13883 harboring either the mcr-1 plasmid (pmcr-1) or the vector control (pBCSK) ATCC 13883. Bacterial fitness characteristics of mcr-1 acquisition were evaluated. Differentiated human monocytes (THP-1s) were stimulated with KP bacterial strains or purified LPS from both parent isolates and isolates harboring mcr-1. Cell culture supernatants were analyzed for cytokine production. A bacterial pneumonia model in WT C57/BL6J mice was used to monitor immune cell recruitment, cytokine induction, and bacterial clearance in the bronchoalveolar lavage fluid (BALF). Isolates harboring mcr-1 had increased colistin MIC compared to the parent isolates but did not alter bacterial fitness. Few differences in cytokines were observed with purified LPS from mcr-1 expressing bacteria in vitro. However, in a mouse pneumonia model, no bacterial clearance defect was observed between pmcr-1-harboring KP and parent isolates. Consistently, no differences in cytokine production or immune cell recruitment in the BALF were observed, suggesting that other mechanisms outweigh the effect of these lipid A mutations in LPS.


Asunto(s)
Antibacterianos , Colistina , Modelos Animales de Enfermedad , Inmunidad Innata , Infecciones por Klebsiella , Klebsiella pneumoniae , Lípido A , Animales , Klebsiella pneumoniae/inmunología , Klebsiella pneumoniae/efectos de los fármacos , Colistina/farmacología , Lípido A/inmunología , Ratones , Infecciones por Klebsiella/inmunología , Infecciones por Klebsiella/microbiología , Humanos , Antibacterianos/farmacología , Farmacorresistencia Bacteriana/genética , Neumonía Bacteriana/inmunología , Neumonía Bacteriana/microbiología , Ratones Endogámicos C57BL , Citocinas/metabolismo , Líquido del Lavado Bronquioalveolar/inmunología , Líquido del Lavado Bronquioalveolar/microbiología , Femenino
2.
Int J Biol Macromol ; 267(Pt 1): 131468, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38599432

RESUMEN

In this work, the changes in the composition of the flours and in the morphological, structural, thermal, vibrational, rheological, and functional properties of the isolated lentil starch during the germination process were investigated. The fiber, fat, and ash content of the flours decreased and the protein content increased, while the apparent amylose content of the starch granules remained constant. Using scanning electron microscopy (SEM), the starch granules remained intact during germination, and no enzymatic activity of α- and ß-amylases was observed. X-ray diffraction shows that the starch has nanocrystals with hexagonal structure which predominate over the nanocrystals with orthorhombic structure and are classified as C-type starch. The most important result is that these nanocrystals do not play an important role during germination. As the germination time progresses, differential scanning calorimetry (DSC) shows a decrease in the gelatinization temperature (Tp) of the starch, ranging from 70.34 ± 0.25 °C for the native lentil starch to values of 67.16 ± 0.37 °C for the starch on the fourth day of germination (ILS4), this transition being related to the solvation of the nanocrystals. On the other hand, the pasting profiles show no significant changes during germination, indicating that no significant changes in starch content occur during germination. Starch degradation is essential for the production of malt for fermented beverages. This fact makes sprouted lentils not a candidate for the short-term fermentation required in the beverage industry.


Asunto(s)
Germinación , Lens (Planta) , Almidón , Lens (Planta)/química , Almidón/química , Almidón/metabolismo , Fenómenos Químicos , Amilosa/química , Temperatura , Reología
4.
Chem Biodivers ; 20(3): e202200554, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36799136

RESUMEN

The optimized geometry of palbociclib, (PD 0332991) (8-cyclopentyl-6-ethanoyl-5-methyl-2-(5-(piperazin-1-yl)pyridin-2-ylamino)pyrido[2,3-d]pyrimidin-7(8H)-one), electrostatic potential map, molecular orbitals were calculated using the density functional theory. The geometry was used in a molecular docking study of palbociclib-kinase complexes, results could be explained by the charge of the nitrogen and oxygen atoms within the palbociclib. Energy gap of HOMO-LUMO surfaces, could help to explain the reactivity of the ligand and the hydrogen bonding with three different kinases, two of CDK6 and one of CDK4 type. Docking results are similar and complementary with literature reports using molecular dynamics, were hydrogen bonding was obtained and analyzed. The promiscuity of three kinases with palbociclib was detected by the docking results, thus, palbociclib could be used in other types of cancer besides myeloid leukemia. Some similarities are found with CDK4/CDK6 kinases which allow us to determine that palbociclib could be used to control other resistant inhibitor types of cancer.


Asunto(s)
Neoplasias , Humanos , Simulación del Acoplamiento Molecular , Piperazinas/farmacología , Piridinas/farmacología , Inhibidores de Proteínas Quinasas/farmacología
5.
Pharm Nanotechnol ; 11(2): 194-207, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36278457

RESUMEN

OBJECTIVE: The objective of this study is to produce a geo-referenced map of the status of R&D in COVID-related studies in the world. METHODS: Spatial mapping of bibliometric data of Cortellis Drug Discovery Intelligence through a spatial bibliometric model with the aid of a GIS (Geographic Information System) called ArcGIS and the software. RESULTS: We show the countries that have the most studies related to COV ID-19 and their degree of collaboration. No drug discovery-related activity was found in South America and Africa. A geo-referenced map of the most active countries in COVID research was constructed as well as conceptual maps of the 11 most representative drugs employed for COVID treatment. CONCLUSION: The georeferenced conceptual maps produced in the present report allow not only to better understand the leading institutions in R&D in COVID-19 related drugs but also to visualize their interactions and research relationships. This could offer, in addition to a coherent, organized multinational effort, the possibility of searching for other drugs that have been employed for other diseases and that, in terms of their conceptual relations, could represent some possibilities for treating the coronavirus SARS-2.


Asunto(s)
COVID-19 , Humanos , SARS-CoV-2 , Bibliometría
6.
J Opioid Manag ; 18(5): 399-405, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36226780

RESUMEN

The conceptual structure of opioids, based on the bibliometric analysis of 4,935 articles of the Web of Science using the following indices: Science Citation Index Expanded (SCI-EXPANDED), Social Sciences Citation Index (SSCI), Conference Proceedings Citation Index-Science (CPCI-S), Conference Proceedings Citation Index- Social Science and Humanities (CPCI-SSH), Book Citation Index-Science (BKCI-S), Book Citation Index-Social Sciences and Humanities (BKCI-SSH) and Emerging Sources Citation Index (ESCI), was constructed. We analyzed the available articles with the words "Opioids" and "Cancer." We show the evolution and the state of the art in countries where these treatments are implemented. The results were processed identifying the most cited articles to extract the main connections and frequencies of keywords, authors, journals, countries, institutions, and their tendencies and their connection and degree of collaboration. The temporal tendencies, the word cloud, the keyword network, the evolution of words, author's production, and the scientific production by country are analyzed in terms of the increasing frequency in which opioids are employed to treat both cancerous and non-cancerous pain.


Asunto(s)
Analgésicos Opioides , Neoplasias , Analgésicos Opioides/efectos adversos , Bibliometría , Humanos , Dolor
7.
Epilepsia ; 63(11): 2981-2993, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-36106377

RESUMEN

OBJECTIVE: More than one third of appropriately treated patients with epilepsy have continued seizures despite two or more medication trials, meeting criteria for drug-resistant epilepsy (DRE). Accurate and reliable identification of patients with DRE in observational data would enable large-scale, real-world comparative effectiveness research and improve access to specialized epilepsy care. In the present study, we aim to develop and compare the performance of computable phenotypes for DRE using the Observational Medical Outcomes Partnership (OMOP) Common Data Model. METHODS: We randomly sampled 600 patients from our academic medical center's electronic health record (EHR)-derived OMOP database meeting previously validated criteria for epilepsy (January 2015-August 2021). Two reviewers manually classified patients as having DRE, drug-responsive epilepsy, undefined drug responsiveness, or no epilepsy as of the last EHR encounter in the study period based on consensus definitions. Demographic characteristics and codes for diagnoses, antiseizure medications (ASMs), and procedures were tested for association with DRE. Algorithms combining permutations of these factors were applied to calculate sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for DRE. The F1 score was used to compare overall performance. RESULTS: Among 412 patients with source record-confirmed epilepsy, 62 (15.0%) had DRE, 163 (39.6%) had drug-responsive epilepsy, 124 (30.0%) had undefined drug responsiveness, and 63 (15.3%) had insufficient records. The best performing phenotype for DRE in terms of the F1 score was the presence of ≥1 intractable epilepsy code and ≥2 unique non-gabapentinoid ASM exposures each with ≥90-day drug era (sensitivity = .661, specificity = .937, PPV = .594, NPV = .952, F1 score = .626). Several phenotypes achieved higher sensitivity at the expense of specificity and vice versa. SIGNIFICANCE: OMOP algorithms can identify DRE in EHR-derived data with varying tradeoffs between sensitivity and specificity. These computable phenotypes can be applied across the largest international network of standardized clinical databases for further validation, reproducible observational research, and improving access to appropriate care.


Asunto(s)
Epilepsia Refractaria , Epilepsia , Humanos , Registros Electrónicos de Salud , Epilepsia Refractaria/diagnóstico , Epilepsia Refractaria/tratamiento farmacológico , Bases de Datos Factuales , Recolección de Datos , Algoritmos , Epilepsia/diagnóstico , Epilepsia/tratamiento farmacológico
8.
Sci Rep ; 12(1): 9109, 2022 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-35650235

RESUMEN

The COVID-19 pandemic has caused a multi-scale impact on the world population that started from a nano-scale respiratory virus and led to the shutdown of macro-scale economies. Direct transmission of SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) and its variants through aerosolized droplets is a major contributor towards increasing cases of this infection. To curb the spread, one of the best engineered solutions is the use of face masks to prevent the passage of infectious saliva micro-droplets from an infected person to a healthy person. The commercially available masks are single use, passive face-piece filters. These become difficult to breathe in during strenuous activities. Also, they need to be disposed regularly due to accumulation of unwanted particulate and pathogens over time. Frequent disposal of these masks is unsustainable for the environment. In this study, we have proposed a novel design for a filter for enhanced virus filtration, better breathability, and virus inactivation over time. The filter is called Hy-Cu named after its (Hy) drophobic properties and another significant layer comprises of copper (Cu). The breathability (pressure drop across filter) of Hy-Cu is tested and compared with widely used surgical masks and KN95 masks, both experimentally and numerically. The results show that the Hy-Cu filter offers at least 10% less air resistance as compared to commercially available masks. The experimental results on virus filtration and inactivation tests using MS2 bacteriophage (a similar protein structure as SARS-CoV-2) show that the novel filter has 90% filtering efficiency and 99% virus inactivation over a period of 2 h. This makes the Hy-Cu filter reusable and a judicious substitute to the single use masks.


Asunto(s)
COVID-19 , Pandemias , COVID-19/prevención & control , Virus ADN , Filtración , Humanos , Levivirus , SARS-CoV-2
9.
Artículo en Inglés | MEDLINE | ID: mdl-35742489

RESUMEN

The COVID-19 pandemic has resulted in high demand for disinfection technologies. However, the corresponding spray technologies are still not completely optimized for disinfection purposes. There are important problems, like the irregular coverage and dripping of disinfectant solutions on hard and vertical surfaces. In this study, we highlight two major points. Firstly, we discuss the effectiveness of the electrostatic spray deposition (ESD) of nanoparticle-based disinfectant solutions for systematic and long-lasting disinfection. Secondly, we show that, based on the type of material of the substrate, the effectiveness of ESD varies. Accordingly, 12 frequently touched surface materials were sprayed using a range of electrostatic spray system parameters, including ion generator voltage, nozzle spray size and distance of spray. It was observed that for most cases, the surfaces become completely covered with the nanoparticles within 10 s. Acrylic, Teflon, PVC, and polypropylene surfaces show a distinct effect of ESD and non-ESD sprays. The nanoparticles form a uniform layer with better surface coverage in case of electrostatic deposition. Quantitative variations and correlations show that 1.5 feet of working distance, an 80 µm spray nozzle diameter and an ion generator voltage of 3-7 kV ensures a DEF (differential electric field) that corresponds to an optimized charge-to-mass ratio, ensuring efficient coverage of nanoparticles.


Asunto(s)
COVID-19 , Desinfectantes , COVID-19/prevención & control , Desinfección/métodos , Humanos , Pandemias/prevención & control , Electricidad Estática
10.
Lancet Reg Health Am ; 12: 100269, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35539820

RESUMEN

Background: This study aimed to describe the clinical characteristics of maternal deaths associated with COVID-19 registered in a collaborative Latin-American multi-country database. Methods: This was an observational study implemented from March 1st 2020 to November 29th 2021 in eight Latin American countries. Information was based on the Perinatal Information System from the Latin American Center for Perinatology, Women and Reproductive Health. We summarized categorical variables as frequencies and percentages and continuous variables into median with interquartile ranges. Findings: We identified a total of 447 deaths. The median maternal age was 31 years. 86·4% of women were infected antepartum, with most of the cases (60·3%) detected in the third trimester of pregnancy. The most frequent symptoms at first consultation and admission were dyspnea (73·0%), fever (69·0%), and cough (59·0%). Organ dysfunction was reported in 90·4% of women during admission. A total of 64·8% women were admitted to critical care for a median length of eight days. In most cases, the death occurred during the puerperium, with a median of seven days between delivery and death. Preterm delivery was the most common perinatal complication (76·9%) and 59·9% were low birth weight. Interpretation: This study describes the characteristics of maternal deaths in a comprehensive multi-country database in Latin America during the COVID-19 pandemic. Barriers faced by Latin American pregnant women to access intensive care services when required were also revealed. Decision-makers should strengthen severity awareness, and referral strategies to avoid potential delays. Funding: Latin American Center for Perinatology, Women and Reproductive Health.


Antecedentes: Este estudio tuvo el objetivo de describir las características clínicas de las muertes maternas asociadas a COVID-19 registradas en una base de datos latinoamericana multipaís. Métodos: Se implementó un estudio observacional descriptivo en el que participaron ochos países Latinoamericanos desde el 1ero de marzo 2020 al 29 de noviembre 2021. La información se obtuvo del Sistema Informático Perinatal del Centro Latino Americano de Perinatología, Salud de la Mujer y Reproductiva. Presentamos las variables categóricas como frecuencias y porcentajes y las variables continuas en medianas con rangos inter cuartiles. Resultados: Identificamos un total de 447 muertes. La mediana de edad materna fue de 31 años. 86·4% de las mujeres se infectaron ante del parto, siendo la mayoría de los casos detectados en el tercer trimestre del embarazo (60·3%). Los síntomas más frecuentes en la primera consulta y la admisión fueron disnea (73·0%), fiebre (69·0%), y tos (59·0%). Se reportaron disfunciones orgánicas en 90·4% de las mujeres durante la admisión. Un total de 64·8% de las mujeres fueron ingresadas a cuidados críticos por una mediana de ocho días de estadía. En la mayoría de los casos la muerte ocurrió durante el puerperio, con una media de siete días entre el parto y su ocurrencia. El parto prematuro fue la complicación perinatal más frecuente (76·9%) y 59·9% tuvo bajo peso al nacer. Interpretación: Este estudio describe las características de las muertes maternas durante la pandemia por COVID-19 a partir de una base colaborativa multipaís. Se observaron barreras para el acceso a cuidados intensivos. Los tomadores de decisión deberían trabajar en el fortalecimiento de la conciencia de gravedad, y en estrategias de referencia para evitar potenciales demoras. Financiamiento: Centro Latino Americano de Perinatología, Salud de la Mujer y Reproductiva.

11.
Epilepsy Behav ; 129: 108630, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-35276502

RESUMEN

INTRODUCTION: Efforts to characterize variability in epilepsy treatment pathways are limited by the large number of possible antiseizure medication (ASM) regimens and sequences, heterogeneity of patients, and challenges of measuring confounding variables and outcomes across institutions. The Observational Health Data Science and Informatics (OHDSI) collaborative is an international data network representing over 1 billion patient records using common data standards. However, few studies have applied OHDSI's Common Data Model (CDM) to the population with epilepsy and none have validated relevant concepts. The goals of this study were to demonstrate the feasibility of characterizing adult patients with epilepsy and ASM treatment pathways using the CDM in an electronic health record (EHR)-derived database. METHODS: We validated a phenotype algorithm for epilepsy in adults using the CDM in an EHR-derived database (2001-2020) against source records and a prospectively maintained database of patients with confirmed epilepsy. We obtained the frequency of all antecedent conditions and procedures for patients meeting the epilepsy phenotype criteria and characterized ASM exposure sequences over time and by age and sex. RESULTS: The phenotype algorithm identified epilepsy with 73.0-85.0% positive predictive value and 86.3% sensitivity. Many patients had neurologic conditions and diagnoses antecedent to meeting epilepsy criteria. Levetiracetam incrementally replaced phenytoin as the most common first-line agent, but significant heterogeneity remained, particularly in second-line and subsequent agents. Drug sequences included up to 8 unique ingredients and a total of 1,235 unique pathways were observed. CONCLUSIONS: Despite the availability of additional ASMs in the last 2 decades and accumulated guidelines and evidence, ASM use varies significantly in practice, particularly for second-line and subsequent agents. Multi-center OHDSI studies have the potential to better characterize the full extent of variability and support observational comparative effectiveness research, but additional work is needed to validate covariates and outcomes.


Asunto(s)
Registros Electrónicos de Salud , Epilepsia , Bases de Datos Factuales , Epilepsia/diagnóstico , Epilepsia/tratamiento farmacológico , Estudios de Factibilidad , Humanos , Levetiracetam
12.
Cell Rep ; 35(9): 109196, 2021 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-34077733

RESUMEN

Klebsiella pneumoniae ST258 is a human pathogen associated with poor outcomes worldwide. We identify a member of the acyltransferase superfamily 3 (atf3), enriched within the ST258 clade, that provides a major competitive advantage for the proliferation of these organisms in vivo. Comparison of a wild-type ST258 strain (KP35) and a Δatf3 isogenic mutant generated by CRISPR-Cas9 targeting reveals greater NADH:ubiquinone oxidoreductase transcription and ATP generation, fueled by increased glycolysis. The acquisition of atf3 induces changes in the bacterial acetylome, promoting lysine acetylation of multiple proteins involved in central metabolism, specifically Zwf (glucose-6 phosphate dehydrogenase). The atf3-mediated metabolic boost leads to greater consumption of glucose in the host airway and increased bacterial burden in the lung, independent of cytokine levels and immune cell recruitment. Acquisition of this acyltransferase enhances fitness of a K. pneumoniae ST258 isolate and may contribute to the success of this clonal complex as a healthcare-associated pathogen.


Asunto(s)
Aciltransferasas/metabolismo , Infecciones por Klebsiella/enzimología , Infecciones por Klebsiella/microbiología , Klebsiella pneumoniae/enzimología , Klebsiella pneumoniae/fisiología , Infecciones del Sistema Respiratorio/enzimología , Infecciones del Sistema Respiratorio/microbiología , Acetilación , Animales , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Carbapenémicos/farmacología , Ciclo del Ácido Cítrico , Eliminación de Gen , Glucosa/metabolismo , Glucólisis/efectos de los fármacos , Klebsiella pneumoniae/crecimiento & desarrollo , Klebsiella pneumoniae/aislamiento & purificación , Lípido A/metabolismo , Pulmón/efectos de los fármacos , Pulmón/microbiología , Pulmón/patología , Lisina/metabolismo , Masculino , Metaboloma/efectos de los fármacos , Metabolómica , Ratones Endogámicos C57BL , Filogenia , Procesamiento Proteico-Postraduccional/efectos de los fármacos
13.
Food Chem ; 315: 126241, 2020 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-32014667

RESUMEN

Chemical modification with octenyl succinic anhydride (OSA) helps to control the physicochemical and thermal properties of isolated starches. The main objective, herein, was to partially characterize modified starches from Dominico-Harton plantain and FHIA 21 planted in Colombia. The highest degree of substitution was found in FHIA 21 (0.020) starch with 3% OSA and 4-h reaction at room temperature. The grain morphology was not affected, but small changes on the surface were evident. Both modified starches reported absorption bands in the IR at 1566 and 1738 cm-1, proper for these types of starch derivatives. The hexagonal and monoclinic structures of starch were altered through chemical modification. In the bending curves, a drastic decrease in the viscosity of the modified starches was observed with respect to the native one. The gelatinization temperatures of the modified starches were similar to those of the isolated starches.


Asunto(s)
Plantago/química , Almidón/química , Amilosa/análisis , Colombia , Microscopía Electrónica de Rastreo , Plantago/crecimiento & desarrollo , Almidón/análogos & derivados , Anhídridos Succínicos/química , Viscosidad , Difracción de Rayos X
14.
Am J Transl Res ; 11(1): 210-217, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30787980

RESUMEN

Computed tomography imaging of the temporomandibular joint was carried out in 22 previously-diagnosed arthritis patients (3 men, 19 women). This descriptive, cross-sectional observational, qualitative study allowed to characterize the type of condylar morphology condition, the space between temporomandibular joint, the erosion of the cortical and osteophytes formation. The joint characteristics found were cortical erosion, osteophytes and decrease of joint space, which reveals, for the first time in the literature, a correlation between arthritis and temporomandibular joint disease.

15.
Am J Hum Genet ; 103(3): 377-388, 2018 09 06.
Artículo en Inglés | MEDLINE | ID: mdl-30146127

RESUMEN

Coronary artery disease (CAD) is the leading cause of death globally. Genome-wide association studies (GWASs) have identified more than 95 independent loci that influence CAD risk, most of which reside in non-coding regions of the genome. To interpret these loci, we generated transcriptome and whole-genome datasets using human coronary artery smooth muscle cells (HCASMCs) from 52 unrelated donors, as well as epigenomic datasets using ATAC-seq on a subset of 8 donors. Through systematic comparison with publicly available datasets from GTEx and ENCODE projects, we identified transcriptomic, epigenetic, and genetic regulatory mechanisms specific to HCASMCs. We assessed the relevance of HCASMCs to CAD risk using transcriptomic and epigenomic level analyses. By jointly modeling eQTL and GWAS datasets, we identified five genes (SIPA1, TCF21, SMAD3, FES, and PDGFRA) that may modulate CAD risk through HCASMCs, all of which have relevant functional roles in vascular remodeling. Comparison with GTEx data suggests that SIPA1 and PDGFRA influence CAD risk predominantly through HCASMCs, while other annotated genes may have multiple cell and tissue targets. Together, these results provide tissue-specific and mechanistic insights into the regulation of a critical vascular cell type associated with CAD in human populations.


Asunto(s)
Enfermedad de la Arteria Coronaria/genética , Vasos Coronarios/fisiología , Regulación de la Expresión Génica/genética , Predisposición Genética a la Enfermedad/genética , Miocitos del Músculo Liso/fisiología , Sitios de Carácter Cuantitativo/genética , Línea Celular , Estudio de Asociación del Genoma Completo/métodos , Genómica/métodos , Humanos , Polimorfismo de Nucleótido Simple/genética , Riesgo
16.
PLoS One ; 12(5): e0178293, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28542584

RESUMEN

In this paper, we have identified and analyzed the emergence, structure and dynamics of the paradigmatic research fronts that established the fundamentals of the biomedical knowledge on HIV/AIDS. A search of papers with the identifiers "HIV/AIDS", "Human Immunodeficiency Virus", "HIV-1" and "Acquired Immunodeficiency Syndrome" in the Web of Science (Thomson Reuters), was carried out. A citation network of those papers was constructed. Then, a sub-network of the papers with the highest number of inter-citations (with a minimal in-degree of 28) was selected to perform a combination of network clustering and text mining to identify the paradigmatic research fronts and analyze their dynamics. Thirteen research fronts were identified in this sub-network. The biggest and oldest front is related to the clinical knowledge on the disease in the patient. Nine of the fronts are related to the study of specific molecular structures and mechanisms and two of these fronts are related to the development of drugs. The rest of the fronts are related to the study of the disease at the cellular level. Interestingly, the emergence of these fronts occurred in successive "waves" over the time which suggest a transition in the paradigmatic focus. The emergence and evolution of the biomedical fronts in HIV/AIDS research is explained not just by the partition of the problem in elements and interactions leading to increasingly specialized communities, but also by changes in the technological context of this health problem and the dramatic changes in the epidemiological reality of HIV/AIDS that occurred between 1993 and 1995.


Asunto(s)
Investigación Biomédica/estadística & datos numéricos , Infecciones por VIH/patología , Fármacos Anti-VIH/uso terapéutico , Bibliometría , Investigación Biomédica/historia , Investigación Biomédica/organización & administración , VIH/efectos de los fármacos , VIH/fisiología , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/fisiopatología , Historia del Siglo XX , Humanos , Modelos Teóricos
17.
IET Nanobiotechnol ; 10(5): 301-307, 2016 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-27676378

RESUMEN

A green facile method has been successfully used for the synthesis of graphene oxide sheets decorated with silver nanoparticles (rGO/AgNPs), employing graphite oxide as a precursor of graphene oxide (GO), AgNO3 as a precursor of Ag nanoparticles (AgNPs), and geranium (Pelargonium graveolens) extract as reducing agent. Synthesis was accomplished using the weight ratios 1:1 and 1:3 GO/Ag, respectively. The synthesised nanocomposites were characterised by scanning electron microscopy, transmission electron microscopy, atomic force microscopy, X-ray diffraction, UV-visible spectroscopy, Raman spectroscopy, energy dispersive X-ray spectroscopy and thermogravimetric analysis. The results show a more uniform and homogeneous distribution of AgNPs on the surface of the GO sheets with the weight ratio 1:1 in comparison with the ratio 1:3. This eco-friendly method provides a rGO/AgNPs nanocomposite with promising applications, such as surface enhanced Raman scattering, catalysis, biomedical material and antibacterial agent.

18.
Microb Cell Fact ; 15(1): 161, 2016 Sep 22.
Artículo en Inglés | MEDLINE | ID: mdl-27659593

RESUMEN

BACKGROUND: Melanins comprise a chemically-diverse group of polymeric pigments whose function is related to protection against physical and chemical stress factors. These polymers have current and potential applications in the chemical, medical, electronics and materials industries. The biotechnological production of melanins offers the possibility of obtaining these pigments in pure form and relatively low cost. In this study, Escherichia coli strains were engineered to evaluate the production of melanin from supplemented catechol or from glycerol-derived catechol produced by an Escherichia coli strain generated by metabolic engineering. RESULTS: It was determined that an improved mutant version of the tyrosinase from Rhizobium etli (MutmelA), could employ catechol as a substrate to generate melanin. Strain E. coli W3110 expressing MutmelA was grown in bioreactor batch cultures with catechol supplemented in the medium. Under these conditions, 0.29 g/L of catechol melanin were produced. A strain with the capacity to synthesize catechol melanin from a simple carbon source was generated by integrating the gene MutmelA into the chromosome of E. coli W3110 trpD9923, that has been modified to produce catechol by the expression of genes encoding a feedback inhibition resistant version of 3-deoxy-D-arabino-heptulosonate 7-phosphate synthase, transketolase and anthranilate 1,2-dioxygenase from Pseudomonas aeruginosa PAO1. In batch cultures with this strain employing complex medium with 40 g/L glycerol as a carbon source, 1.21 g/L of catechol melanin were produced. The melanin was analysed by employing Fourier transform infrared spectroscopy, revealing the expected characteristics for a catechol-derived polymer. CONCLUSIONS: This constitutes the first report of an engineered E. coli strain and a fermentation process for producing a catechol melanin from a simple carbon source (glycerol) at gram level, opening the possibility of generating a large quantity of this polymer for its detailed characterization and the development of novel applications.

19.
Curr Med Chem ; 23(26): 3000-3012, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27530406

RESUMEN

An innovative approach to analyze the complexity of translating novel molecular entities and nanomaterials into pharmaceutical alternatives (i.e., knowledge translation, KT) is discussed. First, some key concepts on the organization and translation of the biomedical knowledge (paradigms, homophily, power law distributions, hierarchy, modularity, and research fronts) are reviewed. Then, we propose a model for the knowledge translation (KT) in Drug Discovery that considers the complexity of interdisciplinary communication. Specifically, we address two highly relevant aspects: 1) A successful KT requires the emergence of organized bodies of inter-and transdisciplinary research, and 2) The hierarchical and modular topological organization of these bodies of knowledge. We focused on a set of previously-published studies on KT which rely on a combination of network analysis and computer-assisted analysis of the contents of scientific literature and patents. The selected studies provide a duo of complementary perspectives: the demand of knowledge (cervical cancer and Ebola hemorrhagic fever) and the supply of knowledge (liposomes and nanoparticles to treat cancer and the paradigmatic Doxil, the first nano- drug to be approved).


Asunto(s)
Diseño de Fármacos , Investigación Biomédica Traslacional , Antineoplásicos/administración & dosificación , Antineoplásicos/química , Portadores de Fármacos/química , Humanos , Liposomas/química , Nanoestructuras/química , Neoplasias/tratamiento farmacológico
20.
Springerplus ; 5(1): 918, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27386362

RESUMEN

Four spatial estimation techniques available in commercial computational packages are evaluated and compared, namely: regularized splines interpolation, tension splines interpolation, inverse distance weighted interpolation, and ordinary Kriging estimation, in order to establish the best representation for the shallow stratigraphic configuration in the city of Aguascalientes, in Central Mexico. Data from 478 sample points along with the software ArcGIS (Environmental Systems Research Institute, Inc. (ESRI), ArcGIS, ver. 9.3, Redlands, California 2008) to calculate the spatial estimates. Each technique was evaluated based on the root mean square error, calculated from a validation between the generated estimates and measured data from 64 sample points which were not used in the spatial estimation process. The present study shows that, for the estimation of the hard-soil layer, ordinary Kriging offered the best performance among the evaluated techniques.

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