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Intramolecular vibrational energy redistribution (IVR) plays a significant role in cavity-modified chemical reaction rates. As such, understanding the fundamental mechanisms by which the cavity modifies the IVR pathways is a fundamental step toward engineering the effect of the confined electromagnetic modes on the outcome of chemical processes. Here we consider an ensemble of M two-mode molecules with intramolecular anharmonic couplings interacting with an infrared cavity mode and consider their quantum dynamics and infrared spectra. Polaritonic Fermi resonances involving fundamental and overtone states of the polaritonic subsystem mediate efficient energy transfer pathways between otherwise off-resonant molecular states. These pathways are of collective nature, yet enabled by the intramolecular anharmonic couplings. Hence, through polaritonic Fermi resonances, cavity excitation can efficiently spread toward low-frequency modes while becoming delocalized over several molecules.
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Alzheimer's disease (AD) is characterized by deficits in olfaction and olfactory pathology preceding diagnosis of dementia. Here we analyzed differential gene and protein expression in the olfactory bulb (OB) and tract (OT) of familial AD (FAD) individuals carrying the autosomal dominant presenilin 1 E280A mutation. Compared to control, FAD OT had increased immunostaining for ß-amyloid (Aß) and CD68 in high and low myelinated regions, as well as increased immunostaining for Iba1 in the high myelinated region. In FAD samples, RNA sequencing showed: (1) viral infection in the OB; (2) inflammation in the OT that carries information via entorhinal cortex from the OB to hippocampus, a brain region essential for learning and memory; and (3) decreased oligodendrocyte deconvolved transcripts. Interestingly, spatial proteomic analysis confirmed altered myelination in the OT of FAD individuals, implying dysfunction of communication between the OB and hippocampus. These findings raise the possibility that viral infection and associated inflammation and dysregulation of myelination of the olfactory system may disrupt hippocampal function, contributing to acceleration of FAD progression.
Asunto(s)
Enfermedad de Alzheimer , Virosis , Humanos , Enfermedad de Alzheimer/metabolismo , Proteómica , Péptidos beta-Amiloides/metabolismo , Bulbo Olfatorio/metabolismo , Inflamación/genética , Inflamación/patología , Virosis/patología , Presenilina-1/genética , Presenilina-1/metabolismoRESUMEN
In response to brain insults, astrocytes become reactive, promoting protection and tissue repair. However, astroglial reactivity is typical of brain pathologies, including Alzheimer's disease (AD). Considering the heterogeneity of the reactive response, the role of astrocytes in the course of different forms of AD has been underestimated. Colombia has the largest human group known to have familial AD (FAD). This group carries the autosomal dominant and fully penetrant mutation E280A in PSEN1, which causes early-onset AD. Recently, our group identified an E280A carrier who did not develop FAD. The individual was homozygous for the Christchurch mutation R136S in APOE3 (APOEch). Remarkably, APOE is the main genetic risk factor for developing sporadic AD (SAD) and most of cerebral ApoE is produced by astroglia. Here, we characterized astrocyte properties related to reactivity, glutamate homeostasis, and structural integrity of the gliovascular unit (GVU), as factors that could underlie the pathogenesis or protection of AD. Specifically, through histological and 3D microscopy analyses of postmortem samples, we briefly describe the histopathology and cytoarchitecture of the frontal cortex of SAD, FAD, and APOEch, and demonstrate that, while astrodegeneration and vascular deterioration are prominent in SAD, FAD is characterized by hyperreactive-like glia, and APOEch displays the mildest astrocytic and vascular alterations despite having the highest burden of Aß. Notably, astroglial, gliovascular, and vascular disturbances, as well as brain cell death, correlate with the specific astrocytic phenotypes identified in each condition. This study provides new insights into the potential relevance of the gliovasculature in the development and protection of AD. To our knowledge, this is the first study assessing the components of the GVU in human samples of SAD, FAD, and APOEch.
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Enfermedad de Alzheimer , Humanos , Enfermedad de Alzheimer/patología , Apolipoproteína E3/genética , Apolipoproteína E3/metabolismo , Homocigoto , Mutación , Encéfalo/patología , Péptidos beta-Amiloides/metabolismoRESUMEN
A series of novel water-soluble short peptide-bioconjugates containing a ferrocenoyl (Fc) or ruthenocenoyl (Rc) unit was synthesized and characterized to combine the unique activity of ferrocene and the isoelectronic ruthenocene with precisely designed peptide structures. We aim at evaluating these bioconjugates as a new class of OrganoMetallic Short AntiMicrobial Peptides (OM-SAMPs). The series of OM-SAMPs was designed with a set of linear and "head-to-tail" cyclic metallocene-based hexapeptides derived from the homo-sequence H-KKKKKK-NH2 by substitution of lysine (K) by tryptophan (W) and by orthogonal derivatization of the ε-N-amine group of lysine by a metallocene moiety. Peptide conjugates were characterized by RP-HPLC, mass spectrometry (ESI and MALDI-TOF) and circular dichroism (CD) spectroscopy. Gram-positive and Gram-negative antibacterial activity testings were carried out to explore the role of insertion of the metallocene fragment into the peptide, and the effect of the modification of the cationic charge and aromatic residues on the physiochemical properties of these OM-SAMPs. These results show that the insertion of two tryptophan residues and ferrocenoyl/ruthenocenoyl moieties into a linear homo-sequence peptides increase significantly their antibacterial activity with minimum inhibitory concentration values as low as 5 µM for the most active compounds. However, "head-to-tail" cyclic metallocene-based hexapeptides were not active against Gram-negative bacteria up to concentrations of 50 µM. These studies provide a better understanding of the role of structural modifications to enhance antibacterial peptide activity, which is promising for their therapeutic application.
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Antibacterianos/farmacología , Compuestos Ferrosos/farmacología , Metalocenos/farmacología , Oligopéptidos/farmacología , Compuestos Organometálicos/farmacología , Técnicas de Síntesis en Fase Sólida , Antibacterianos/síntesis química , Antibacterianos/química , Compuestos Ferrosos/química , Bacterias Gramnegativas/efectos de los fármacos , Bacterias Grampositivas/efectos de los fármacos , Metalocenos/química , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Oligopéptidos/síntesis química , Oligopéptidos/química , Compuestos Organometálicos/química , Solubilidad , Agua/químicaRESUMEN
Lactic acid bacteria can be considered as natural biopreservative and good biotechnological alternative to food safety. In this study, the antilisterial compounds produced by Enterococcus isolates from the Patagonian environment and their effectiveness for the control of Listeria monocytogenes in a food model were studied. Enterococcus isolates whose cell-free supernatant presented activity against Listeria monocytogenes were identified and evaluated for their virulence factors. The activity of the antimicrobial compounds produced by Enterococcus sp. against Listeria monocytogenes Scott A in meat gravy and ground beef during refrigerated storage was tested. The results indicated that ten Enterococcus isolates presented activity against Listeria monocytogenes and none of the selected strains presented virulence factors. L. monocytogenes in the food models containing the antilisterial compounds produced by Enterococcus sp. has decreased over the days, indicating that these compounds and cultures are an alternative to control the growth of L. monocytogenes in foods.
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Antibacterianos/farmacología , Conservantes de Alimentos/farmacología , Lactobacillales/metabolismo , Listeria monocytogenes/crecimiento & desarrollo , Carne/microbiología , Animales , Antibacterianos/metabolismo , Bovinos , Enterococcus/aislamiento & purificación , Enterococcus/metabolismo , Microbiología de Alimentos , Conservantes de Alimentos/metabolismo , Almacenamiento de Alimentos , Lactobacillales/aislamiento & purificación , Listeria monocytogenes/efectos de los fármacosRESUMEN
Coherent excitation of a molecular ensemble coupled to a common radiation mode can lead to the collective emission of radiation known as superradiance. This collective emission only occurs if there is an entanglement between the molecules in their ground and excited state and can, therefore, serve as a macroscopic measure of coherence in the ensemble. Reported here are wave packet propagations for various pyrazine models of increasing complexity and molecular ensembles thereof. We show that ensemble coherence upon photoexcitation can prevail up to relatively long time scales although the effect can diminish quickly with increasing ensemble size. Coherence can also build up over time and even reemerge after the molecules have passed through a conical intersection. The effect of the pump pulse characteristics on the collective response of the molecular ensemble is also studied. A broadband pulse imprints a large amount of initial coherence to the system, as compared to a longer pulse with a smaller spread in the frequency domain. However, the differential effects arising from a different pulse duration and coherent bandwidth become less prominent if the emission of light from the ensemble takes place after a non-adiabatic decay process.
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The coupling of a molecular ensemble to the confined electromagnetic modes of a microcavity can strongly modify the photophysics and photochemistry of the molecules upon photoexcitation. We investigate here how collective coupling effects lead to modifications of the mechanisms and rates of photochemical processes, in particular, photodissociation and nonradiative decay in NaI and pyrazine, respectively. We show that, after direct excitation into the lower polaritonic states, the lower-energy light-matter hybrid states, the dynamics of the molecular ensemble coupled to light is very similar to the dynamics of the corresponding isolated molecules. Conversely, excitation into the upper polaritonic states results in more complex dynamics that involve as a first step the population transfer toward the manifold of intermediate dark states. These dynamics differ substantially from those of the isolated molecules and may result in measurable time delays for nonradiative decay or excited-state reaction mechanisms. Similarly, we describe how addition of a buffer of nonreactive molecules coupled to the cavity mode can be used to delay the onset of the photochemical processes of the reactive part of the ensemble, where the buffer medium is more effective in inhibiting the reactive process than only reactive molecules in the cavity.
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Resumen Objetivo: Identificar los eventos adversos (EA) reportados por enfermería en algunas unidades de cuidado intensivo (UCI) en Bogotá (Colombia). Método: Se desarrolló un estudio descriptivo, prospectivo. El tamaño de la muestra correspondió a 525pacientes, durante un periodo de 6 meses. El tipo de muestreo fue por criterio; participaron de forma voluntaria 3 instituciones de salud en Bogotá. Para recolectar información se utilizó un formulario digital on-line. Se realizó un análisis descriptivo con distribución de frecuencias absolutas y relativas, utilizando el programa estadístico SPSS Statistics 23.0, versión 2014. Resultados: Se reportaron 594 eventos adversos presentados en 525 pacientes. Los relacionados con el cuidado enfermero ocuparon el primer lugar (38,7 %), seguido del manejo de la vía aérea y la ventilación mecánica (16,1 %) y el manejo de accesos vasculares, sondas y drenajes (14,8 %) y la infección asociada al cuidado (12,6 %). La ocurrencia de estos eventos adversos predominó en hombres con edad promedio de 64,5 años, en unidades de cuidado intensivo médicas, en el turno de la noche y con un TISS-28 de 20-39 puntos. Conclusiones: Los eventos adversos reportados en el estudio que presentan mayor prevalen-cia están relacionados en su mayoría con el cuidado directo al paciente y el de vía aérea; al ser prevenibles indican que se presentaron por alteración en el cumplimiento de los estándares del cuidado.
Abstract Objective: To identify adverse events (AEs) reported by nursing in some intensive care units (ICU) in Bogota. Method: A descriptive, prospective study was developed. The size of the sample consisted of 525 patients over a period of 6 months. The sampling was by convenience, participated voluntarily three health institutions in the city of Bogota. To collect information, digital form on-line. Data was analyzed with SPSS Statistics 23.0, version 2014. Results: 594 reported adverse events in 525patients, related care nurse ranked first (38.7%), followed by airway management and mechanical ventilation (16.1%) and management of vascular access, probes and drains (14.8 %) and infection associated with care (12.6%). the occurrence of these adverse events predominated in men with an average age of 64.5 years in medical intensive care units, on the night shift with a 20-39 TISS-28 points. Conclusions: Adverse Events reported in the present study are more prevalent mostly related to direct patient care and airway, being preventable, was presented they indicate that alteration in compliance with standards of care.
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The deprotection step is crucial in order to secure a good quality product in Fmoc solid phase peptide synthesis. 9-Fluorenylmethoxycarbonyl (Fmoc) removal is achieved by a two-step mechanism reaction favored by the use of cyclic secondary amines; however, the efficiency of the reaction could be affected by side reactions and by-product formation. Several aspects have to be taken into consideration when selecting a deprotection reagent: its physicochemical behavior, basicity (pKa) and polarity, concentration, and time of reaction, toxicity and disposability of residues and, finally, availability of reagents. This report presents a comparison of the performance of three strategies for deprotection using microwave-assisted Fmoc peptide synthesis. Four peptide sequences were synthesized using Rink amide resin with a Liberty Blue™ automated synthesizer and 4-methylpiperidine (4MP), piperidine (PP), and piperazine (PZ) as Fmoc removal reagents. In the first instance all three reagents behaved similarly. A detailed analysis showed a correlation between the hydrophobicity and size of the peptide with the yield and purity of the obtained product. The three reagents are interchangeable, and replacement of piperidine could be advantageous regarding toxicity and reagent handling.
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Péptidos/síntesis química , Técnicas de Síntesis en Fase Sólida , Aminoácidos/química , Cromatografía Líquida de Alta Presión , Fluorenos/química , Cinética , Piperidinas/química , Espectrometría de Masa por Ionización de ElectrosprayRESUMEN
Introducción. La infección por el virus de la inmunodeficiencia humana (VIH) fue la segunda causa de mortalidad en adultos jóvenes residentes en Bucaramanga en 2013, después de las lesiones de causa externa. Objetivo. Establecer el grado de conocimiento sobre mecanismos de transmisión y estrategias de prevención del VIH en estudiantes de 13 a 20 años de colegios de las comunas pobres de Bucaramanga. Metodología. Estudio transversal con estudiantes, escogidos al azar, con encuesta anónima autodiligenciada. En el análisis, se describieron cada variable y modelos binomiales de asociación de las respuestas según edad, sexo, nivel académico y experiencia sexual previa. Resultados. Se encuestaron 729 estudiantes (57% mujeres); el 50,6% de los varones afirmaron haber tenido relaciones sexuales, así como el 31,1% de las mujeres. El 58,6% aseguraron que una persona que se veía saludable podía estar infectada. El 69,1% respondieron que podía transmitirse durante el embarazo; el 39,2%, durante el parto; el 37,7%, con la lactancia; el 79,7%, por medio de jeringas usadas por otros; el 29,5%, por compartir alimentos con personas infectadas; y el 31,7%, por mosquitos. El 70,6% consideraron que podía prevenir el VIH evitando relaciones sexuales; el 67,5%, si eran monógamos; y el 80,0%, usando correctamente condón. La proporción de respuestas adecuadas no estuvo relacionada con mayor nivel académico, edad, género o experiencia sexual. Conclusiones. La calidad del conocimiento sobre mecanismos de transmisión y prevención de la infección por VIH es muy deficiente, a pesar del currículo de educación sexual. El conocimiento no fue mejor en los grados académicos más altos.
Introduction. Human immunodeficiency virus (HIV) infection was the second most common cause of death, after injuries of external causes, among young adults from Bucaramanga in 2013. Objective. To establish the extent of knowledge on HIV mechanisms of transmission prevention strategies among schoolchildren in the age range of 13 to 20 years old from poor districts of Bucaramanga. Methodology. Cross-sectional study among randomly selected schoolchildren using a self-administered anonymous survey. For analysis, each outcome measure and binomial models for the association of answers by age, gender, education level and past sexual experience were described. Results. A survey was administered to 729 students (57% were girls); 50.6% of boys and 31.1% of girls reported having had sexual intercourse. Also, 58.6% stated that a healthy-looking person can have HIV. Besides, 69.1% indicated that HIV can be transmitted during pregnancy; 39.2%, during delivery; 37.7%, through breastfeeding; 79.7%, through needle sharing; 29.5%, by sharing food with someone who has HIV; and 31.7%, by mosquito bites. In addition, 70.6% considered that they could prevent HIV by abstaining from having sexual relationships; 67.5%, by having a single partner; and 80.0%, by wearing condoms correctly. The proportion of adequate answers was not related to a higher education level, age, gender or sexual experience. Conclusions. The quality of knowledge regarding HIV mechanisms of transmission and prevention is very poor, in spite of curricular contents providing sex education. It was observed that knowledge was not greater among those with higher education levels.
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Humanos , Adolescente , Pobreza , Infecciones por VIH/prevención & control , Infecciones por VIH/transmisión , Conocimientos, Actitudes y Práctica en Salud , Colombia , Estudios TransversalesRESUMEN
INTRODUCTION: Human immunodeficiency virus (HIV) infection was the second most common cause of death, after injuries of external causes, among young adults from Bucaramanga in 2013. OBJETIVE: To establish the extent of knowledge on HIV mechanisms of transmission prevention strategies among schoolchildren in the age range of 13 to 20 years old from poor districts of Bucaramanga. METHODOLOGY: Cross-sectional study among randomly selected schoolchildren using a self-administered anonymous survey. For analysis, each outcome measure and binomial models for the association of answers by age, gender, education level and past sexual experience were described. RESULTS: A survey was administered to 729 students (57% were girls); 50.6% of boys and 31.1% of girls reported having had sexual intercourse. Also, 58.6% stated that a healthy-looking person can have HIV. Besides, 69.1% indicated that HIV can be transmitted during pregnancy; 39.2%, during delivery; 37.7%, through breastfeeding; 79.7%, through needle sharing; 29.5%, by sharing food with someone who has HIV; and 31.7%, by mosquito bites. In addition, 70.6% considered that they could prevent HIV by abstaining from having sexual relationships; 67.5%, by having a single partner; and 80.0%, by wearing condoms correctly. The proportion of adequate answers was not related to a higher education level, age, gender or sexual experience. CONCLUSIONS: The quality of knowledge regarding HIV mechanisms of transmission and prevention is very poor, in spite of curricular contents providing sex education. It was observed that knowledge was not greater among those with higher education levels.
INTRODUCCIÓN: La infección por el virus de la inmunodeficiencia humana (VIH) fue la segunda causa de mortalidad en adultos jóvenes residentes en Bucaramanga en 2013, después de las lesiones de causa externa. OBJECTIVO: Establecer el grado de conocimiento sobre mecanismos de transmisión y estrategias de prevención del VIH en estudiantes de 13 a 20 anos de colegios de las comunas pobres de Bucaramanga. METODOLOGÍA: Establecer el grado de conocimiento sobre mecanismos de transmisión y estrategias de prevención del VIH en estudiantes de 13 a 20 anos de colegios de las comunas pobres de Bucaramanga. RESULTADOS: Se encuestaron 729 estudiantes (57% mujeres); el 50,6% de los varones afirmaron haber tenido relaciones sexuales, así como el 31,1% de las mujeres. El 58,6% aseguraron que una persona que se veía saludable podía estar infectada. El 69,1% respondieron que podía transmitirse durante el embarazo; el 39,2%, durante el parto; el 37,7%, con la lactancia; el 79,7%, por medio de jeringas usadas por otros; el 29,5%, por compartir alimentos con personas infectadas; y el 31,7%, por mosquitos. El 70,6% consideraron que podía prevenir el VIH evitando relaciones sexuales; el 67,5%, si eran monógamos; y el 80,0%, usando correctamente condón. La proporción de respuestas adecuadas no estuvo relacionada con mayor nivel académico, edad, género o experiencia sexual. CONCLUSIONES: La calidad del conocimiento sobre mecanismos de transmisión y prevención de la infección por VIH es muy deficiente, a pesar del currículo de educación sexual. El conocimiento no fue mejor en los grados académicos más altos.
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Infecciones por VIH/prevención & control , Infecciones por VIH/transmisión , Conocimientos, Actitudes y Práctica en Salud , Adolescente , Niño , Colombia , Estudios Transversales , Femenino , Humanos , Masculino , Pobreza , Adulto JovenRESUMEN
Objetivo: Comparar in vitro el efecto citotóxico de tres agentes quelantes sobre fibroblastos del ligamento periodontal humano. Materiales y métodos: Se utilizaron cultivos de fibroblastos de ligamento periodontal humano, los cuales fueron colocados en contacto con los agentes quelantes a evaluar (RC-Prep, Glyde, EDTA al 17%) a intervalos de 15, 30 y 60 minutos. Se midió la absorbancia para cada uno de los grupos, para determinar el grado de actividad enzimática, que es indicador de muerte celular. Previo a la cuantificación de la absorbancia se corroboró microscópicamente la formación de los cristales de formazán, los cuales se forman alrededor de los fibroblastos, y su presencia es indicador de integridad de la membrana y de la actividad metabólica. Por microscopia se verificó la formación de cristales de formazan, después de agregar azul de tripán. Resultados: El Glyde mostró mayor grado de citotoxicidad, con una diferencia estadísticamente significativa, al compararlo con EDTA 17% y el RC-PREP. El EDTA presentó mayor citotoxicidad que el RC-PREP a los 15minutos, evento que cambió a los 30 y 60 minutos. Conclusiones: Los agentes quelantes RC-Prep, Glyde y EDTA tienen un efecto citotóxico a nivel de los fibroblastos del ligamento periodontal, siendo el EDTA el de menor efecto citotóxico a los 30 y 60 minutos comparado con RC-Prep y Glyde.
Objectives: To compare in vitro, the cytotoxic effect of three chelating agents on human periodontal ligament fibroblasts, RC-Prep, Glyde and EDTA. Methods: Fibroblast cultures of human periodontal ligament were used, which are placed in contact with chelating agents to evaluate (RC-Prep, Glyde, 17% EDTA) at time intervals of 15,30 and 60 minutes. Absorbance was measured for each group to determine the degree of enzyme activity, which is an indicator of cell death. Prior to the measurement of absorbance was confirmed microscopically, the formation of formazan crystals, which are formed around fibroblasts, and its presence is an indicator of membrane integrity and metabolic activity. Microscopy verified the formation of formazan crystals, after adding trypan blue. Results: Glyde showed greater cytotoxicity with a statistically significant difference when compared with 17% EDTA and RC-PREPchelants. The EDTA showed higher cytotoxicity than the RC-PREP to 15min, and that event changed at 30 and 60 minutes. Conclusion: It was shown experimentally that the chelating agents RC-Prep, EDTA and Glyde have a cytotoxic effect at the periodontal ligament fibroblasts. EDTA has a lowest cytotoxic effect at 30 and 60 minutes compared to RC-Prep and Glyde.
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Erythrocyte binding antigen-160 (EBA-160) protein is a Plasmodium falciparum antigen homologue from the erythrocyte binding protein family (EBP). It has been shown that the EBP family plays a role in parasite binding to the erythrocyte surface. The EBA-160 sequence has been chemically synthesised in seventy 20-mer sequential peptides covering the entire 3D7 protein strain, each of which was tested in erythrocyte binding assays to identify possible EBA-160 functional regions. Five EBA-160 high activity binding peptides (HABPs) specifically binding to erythrocytes with high affinity were identified. Dissociation constants lay between 200 and 460 nM and Hill coefficients between 1.5 and 2.3. Erythrocyte membrane protein binding peptide cross-linking assays using SDS-PAGE showed that these peptides bound specifically to 12, 28, and 44 kDa erythrocyte membrane proteins. The nature of these receptor sites was studied in peptide binding assays using enzyme-treated erythrocytes. HABPs were able to block merozoite in vitro invasion of erythrocytes. HABPs' potential as anti-malarial vaccine candidates is also discussed.