An overview of offset analgesia and the comparison with conditioned pain modulation : a systematic literature review

Background: Offset analgesia (OA) is an increasingly described phenomenon to measure endogenous pain inhibition, in which a greater decrease in pain intensity is experienced than would be predicted by the decrease in painful stimulation. The temporal filtering in this OA phenomenon differs from the spatial filtering in the commonly described conditioned pain modulation (CPM). Yet, the knowledge on the efficacy of OA in chronic pain patients is scarce, compared to CPM efficacy. Objective: This systematic review has been conducted to provide an overview of the current knowledge regarding OA, and to compare it to CPM. Study Design: A systematic review of research studies that investigated the application or mechanisms of OA. Setting: The present study took place at Ghent University and the University of Antwerp. Methods: This systematic review follows the PRISMA guidelines. The electronic databases Pubmed and Web of Science were searched in January 2015. Full text clinical reports addressing OA were included. The checklists for randomized controlled trials, case-control studies, and cohort-studies provided by the Dutch Institute for Healthcare Improvement and the Dutch Cochrane Centre were used to assess methodological quality. The articles received a level of evidence A1, A2, B, C, or D, based on study design and risk of bias. These levels were used to determine the strength of conclusion (level 1 to 4). Results: Seventeen articles met the inclusion criteria. Sixteen studies used quantitative sensory testing to provoke OA; however, differences in protocols are present. OA can function as a non-opioid mediated assessment tool for endogenous pain inhibition, and activates brain regions such as periaqueductal gray (PAG), dorsolateral prefontral cortex, insula, medulla, pons and cerebellum, indicating strong brain derived pain modulation. The primary somatosensory cortex is, conversely, less activated during OA. OA is decreased in neuropathic patients. Nonetheless, evidence for the influence of individual factors on OA is limited. OA and CPM seem to rely on different mechanisms. Limitations: Search strategy was taken wide, wherefore a large variety of research perspectives were included. Conclusions: This systematic review displays OA as a temporal filtering mechanisms that is more brain-derived compared to the spatial assessment method CPM. There is strong evidence for reduced OA in neuropathic patients, however, evidence regarding OA in (sub) acute and central sensitization patients, and the influence of personal factors on OA is currently scarce and needs further investigation

Photochemical Synthesis of the Bioconjugate Folic Acid-Gold Nanoparticles

In this paper we present a rapid and simple onepot method to obtain gold nanoparticles functionalized with folic acid using a photochemistry method. The bioconjugate folic acid-gold nanoparticle was generated in one step using a photo-reduction method, mixing hydrogen tetrachloroaurate with folic acid in different ratios and varying the illumination time of a mercury lamp (λ= 255 nm). Scanning electron microscopy showed a particle size of around 40-50nm and dynamic light scattering exhibited that the zeta potential varies from -41 to -50mV with different illumination times. Storage in the dark at 4°C prolongs the stability of folic acid-gold nanoparticle suspensions to up to 26 days. Ultraviolet visible and Fourier transform infrared spectroscopy showed a surface plasmon band of around 534nm and fluorescence spectroscopy exhibited a quenching effect on gold nanoparticles in the fluorescence emission of folic acid and thus confirmed the conjugation of folic acid to the surface of gold nanoparticles. In this study we demonstrate the use of a photochemistry method to obtain folic acid-gold nanoparticles in a simple and rapid way without the use of surfactants and long reaction times. The photochemical synthesis of FA-AuNPs opens new perspectives for creating novel functional nanomaterials for biomedical applications

Orientation of Pterin-6-Carboxylic Acid on Gold Capped Silicon Nanopillars Platforms: Surface Enhanced Raman Spectroscopy and Density Functional Theory Studies

The orientation of pterin-6-carboxylic acid on gold nanopillars was investigated by surface enhanced Raman spectroscopy and density functional theory methods. The experimentally vibrations from pterin-6-COOH free and attached to the Au surface display vibration features indicating chemical interaction of the pterin with the metal surface. The spectral feature evidenced that the pterin would adsorb on gold surface with a "lying down" configuration through the high intensity vibration of NH scissoring and rocking OH modes. The orientation study of pterins on gold nanopillars presented herein is believed to lead to new applications in biosensing field for detecting pterins of physiological importance

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Nanostructured Titanium Dioxide Surfaces for Electrochemical Biosensing

TiO2 electrochemical biosensors represent an option for biomolecules recognition associated with diseases, food or environmental contaminants, drug interactions and related topics. The relevance of TiO2 biosensors is due to the high selectivity and sensitivity that can be achieved. The development of electrochemical biosensors based on nanostructured TiO2 surfaces requires knowing the signal extracted from them and its relationship with the properties of the transducer, such as the crystalline phase, the roughness and the morphology of the TiO2 nanostructures. Using relevant literature published in the last decade, an overview of TiO2 based biosensors is here provided. First, the principal fabrication methods of nanostructured TiO2 surfaces are presented and their properties are briefly described. Secondly, the different detection techniques and representative examples of their applications are provided. Finally, the functionalization strategies with biomolecules are discussed. This work could contribute as a reference for the design of electrochemical biosensors based on nanostructured TiO2 surfaces, considering the detection technique and the experimental electrochemical conditions needed for a specific analyte.This work was financed by the I-COOP+2018 program of CSIC (ref. COOPA20305).Peer reviewe

Desarrollo de un biosensor para el reconocimiento de receptores de folato

Resumen del trabajo presentado en el 1st Innovative Technologies for Medical Applications, celebrado en Bucaramanga (Colombia), los días 1 y 2 de diciembre de 2022La sobre-expresión de receptores de folato en la superficie celular está relacionada con una anomalía asociada al cáncer epitelial.1,2,3 En este sentido, se desarrolló un biosensor capacitivo que utiliza el ácido fólico como elemento de bio-reconocimiento para la detección de receptores de folato. 4 El detector consiste principalmente en una película delgada de óxidos de Ti-W conjugada al ácido fólico, que funciona como electrodo de trabajo en una configuración de celda electroquímica de tres electrodos. Las interacciones entre el biosensor y los receptores de folato se estudiaron por medio de la determinación de la dureza química a partir de medidas de espectroscopía de capacitancia electroquímica. La película delgada de óxidos de Ti-W se fabricó mediante el método de deposición por láser pulsado y posteriormente, se funcionalizó con ácido fólico. La caracterización de la película antes y después de la funcionalización se realizó por medio de microscopia de fuerzas atómicas, espectroscopía de fotoelectrones emitidos por rayos X, espectroscopía Raman y ángulo de contacto. Los ensayos de reconocimiento de receptores de folato usando el biosensor fabricado mostraron que la señal de respuesta del detector, la dureza química (en términos de la capacitancia electroquímica), es selectiva y directamente proporcional a la concentración de receptores de folato, con un límite de detección de 0.2 nM. Este resultado es prometedor en la aplicación de este tipo de biosensor para el reconocimiento de receptores de folato, especialmente para análisis en el lugar de atención

Experimental analysis of folic acid adsorption on TiO2 thin-films

TiO2 thin-films functionalized with specific biomolecules have been used in the fabrication of highly sensitive and selective electrochemical biosensors focused on detecting a variety of diseases. Among the biosensors of scientific and technological interest are those obtained from the functionalization of nanomaterials with folic acid to recognize folate receptors; their importance lies in the fact that these receptors are overexpressed in most abnormal cells, and their identification can allow the detection of tumor cells and the photothermal treatment of cancer. This work presents a methodology for fabricating TiO2 thin-films and functionalizing them with folic acid. X-ray photoelectron spectroscopy, atomic force microscopy, Raman spectroscopy, and contact angle measurements were used to examine the adsorption of folic acid on TiO2 thin-film surfaces grown by pulsed laser deposition. XPS and Raman analysis indicated that the interaction of folic acid with the TiO2 surface occurred either through the pteridine ring or through the carboxylic groups of the glutamic acid portionThe authors thank the I-COOP+2018 program of CSIC (Ref. No. COOPA20305) and Universidad Industrial de Santander for financial support. Furthermore, we would like to acknowledge teams of Laboratorio de ciencia de superficies and Laboratorio de Espectroscopia of the Parque Tecnológico de Guatiguará at Universidad Industrial de Santander for XPS and Raman analysis. The authors thank Yves Huttel from ICMM-CSIC for his help with additional XPS measurements.Peer reviewe

Deposición por láser pulsado de películas delgadas de TiO2 y su funcionalización con ácido fólico

Trabajo presentado en el 34ª Congreso Latinoamericano de Química (CLAQ2020), celebrado online y presencial en Cartagena de Indias (Colombia), del 11 al 15 de octubre de 2021Las películas delgadas de TiO2 funcionalizadas con biomoléculas específicas se han utilizado en la fabricación de biosensores electroquímicos, altamente sensibles y selectivos [1-2], o como implantes biocompatibles [3]. Entre los biosensores de interés científico y tecnológico se encuentran los obtenidos a partir de la funcionalización de nanomateriales con ácido fólico para el reconocimiento de receptores de folato; su importancia radica en que estos receptores se encuentran sobre-expresados en la mayoría de las células cancerosas y su identificación puede permitir la detección o el tratamiento fototérmico del cáncer [4-5]. En este trabajo, se presenta una metodología para la fabricación de películas delgadas de TiO2 y su funcionalización con ácido fólico. Las películas delgadas de TiO2 se obtuvieron mediante la deposición por láser pulsado a diferentes valores de fluencia de la luz láser entre 1.3 y 2.5 J/m2 a un tiempo de deposición constante de 5 min. La cámara de deposición tenía una presión base de 7.4x10-3 Pa y la deposición de la película se realizó sobre un sustrato de Si a temperatura ambiente, bajo una presión de 4.6 Pa de oxígeno. Las películas se caracterizaron por espectroscopía de fotoelectrones emitidos por rayos X (XPS), microscopia de fuerza atómica (AFM), y espectroscopía Raman, mientras que las películas funcionalizadas con ácido fólico se caracterizaron mediante análisis AFM y espectroscopía Raman. El análisis XPS permitió confirmar la composición química de las películas delgadas de TiO2. Se observó, en las imágenes AFM de las películas obtenidas, que a una mayor fluencia de luz láser el espesor de la película y la rugosidad RMS aumentan. El análisis AFM de las películas funcionalizadas mostraron una disminución de la rugosidad, con respecto a la película sin funcionalizar, indicando que las moléculas de ácido fólico podrían haberse ubicado en los valles de la película. Uno de los principales resultados obtenidos fue la identificación, a partir del análisis de los espectros Raman, de la interacción del ácido fólico con la superficie de TiO2 a través del anillo de pteridina. De esta manera, la metodología reportada permite obtener una película delgada de TiO2 funcionalizada con ácido fólico que puede ensayarse en investigaciones futuras en la detección de células cancerosas.Peer reviewe

Pulsed Laser Deposition of TiO2 thin film and their functionalization with folic acid

Resumen del trabajo presentado en la 3rd Coatings and Interfaces Conference, celebrada en online del 24 al 26 de noviembre de 2021TiO2 thin films and nanostructures functionalized with specific biomolecules have been used in the manufacture of highly sensitive and selective electrochemical biosensors.1 In particular, nanomaterials functionalized with folic acid for detection of folate receptors are highly interesting, because these receptors are over-expressed in most cancer cells and, therefore, their identification can allow the detection and even the photothermal treatment of cancer. 2-3 In this work, a methodology for the manufacture of TiO2 thin films and their functionalization with folic acid is presented. TiO2 thin films were obtained by pulsed laser deposition at different fluence values of the laser light between 1.3 and 2.5 J/cm2 at a constant deposition time of 5 min. The deposition chamber had a base pressure of 7.4x10- 3 Pa and the deposition of the film was carried out on a Si substrate at room temperature, under a pressure of 4.6 Pa of oxygen. Thin films with and without functionalization were characterized by Xray photoelectron spectroscopy (XPS), atomic force microscopy (AFM), and Raman spectroscopy. AFM images of the obtained films show that as the fluence of laser light increases, the thickness and RMS roughness of thin film increases. The AFM analysis of the functionalized films evidenced a decrease in roughness, with respect to the non-functionalized film, indicating that the folic acid molecules were mainly anchored in the valleys of the film. The Raman analysis as by XPS showed evidence of the interaction of folic acid with the surface of TiO2 through the pteridine ring. In this way, the reported methodology allows for obtaining TiO2 thin films functionalized with folic acid that can be tested in future research in the detection of cancer cells

Libro de Proyectos Finales 2021 primer semestre

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