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1.
Chemistry ; 29(10): e202203187, 2023 Feb 16.
Artículo en Inglés | MEDLINE | ID: mdl-36346617

RESUMEN

The on-surface self-assembly of molecules to form holey nanographenes is a promising approach to control the properties of the resulting 2D lattice. Usually, planar molecules are utilized to prepare flat, structurally confined molecular layers, with only a few recent examples of warped precursors. However, control of the superstructures is limited thus far. Herein, we report the temperature-controlled self-assembly of a bowl-shaped, acetylated C3 -symmetric hexaphenyltribenzotriquinacene derivative on Cu(111). Combining scanning tunneling microscopy (STM) and density functional theory (DFT) confirms the formation of highly differing arrangements starting with π-stacked bowl-to-bowl dimers at low coverage at room temperature via chiral honeycomb structures, an intermediate trigonal superstructure, followed by a fully carbon-based, flattened hexagonal superstructure formed by on-surface deacetylation, which is proposed as a precursor for holey graphene networks with unique defect structures.

2.
Phys Chem Chem Phys ; 25(11): 7681-7687, 2023 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-36857662

RESUMEN

Upon deposition on a surface, molecules can undergo a plethora of changes, such as reactions with adsorbates and surface atoms and catalytic decomposition. Since different reaction pathways may coexist, spatially averaging techniques can be insufficient for the characterization and distinction of all on-surface products. Here, we present a study of single phthalocyanine molecules on a Cu(111) surface which was performed using high-resolution low-temperature STM. Upon deposition of metal-free H2Pc, we can identify three distinct molecular species. A thorough investigation reveals that temperature-driven on-surface reactions partially convert H2Pc into H0Pc and CuPc. The individual species are differentiated by their topographic appearance and can unambiguously be identified by their STM-induced rotational behavior. While H2Pc shows a switching between two orientations at low energies, a third orientation can be observed above E > 800 meV, which is induced by tautomerization. Around the Fermi level, the rotational behavior is asymmetric, owing to the excitation of vibrational modes in unoccupied states whereas resonant tunneling occurs in occupied states. A two-step deprotonation of H2Pc confirms that the second species is H0Pc. By comparison with CuPc evaporated on Cu(111), we unambiguously reveal that the third species is indeed CuPc, which exhibits an exceptionally low threshold for rotational switching accompanied by an asymmetric behavior around the Fermi level. Varying the post-annealing temperature, we found a sharp threshold for the H2Pc → CuPc on-surface metalation at around 100 °C. In contrast, the competing process of thermal decomposition from H2Pc to H0Pc only increases weakly.

3.
Phys Chem Chem Phys ; 25(35): 23894-23900, 2023 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-37642506

RESUMEN

We present a study on the excitation of individual vibrational modes with ballistic charge carriers propagating along the Cu(110) surface. By means of the molecular nanoprobe technique, where the reversible switching of a molecule-in this case tautomerization of porphycene-is utilized to detect excitation events, we reveal anisotropic coupling of two distinct vibrational modes to the substrate. The N-H bending mode, excited below |E| ≈ 376 meV, exhibits maxima perpendicular to the rows of the Cu(110) substrate and minima along the rows. In contrast, the N-H stretching mode, excited above |E| ≈ 376 meV, displays maxima along the rows and is constant otherwise. This inversion of the anisotropy reflects the orthogonality between the N-H bending and stretching mode. Additionally, we observe an energy-dependent asymmetry in the propagation direction of charge carriers injected into the Cu(110) surface state. Hereby, the anisotropic band structure results in a correlation between the group velocity and the tunneling probability into electronic states of the substrate.

4.
Bioelectromagnetics ; 43(7): 404-412, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-36335604

RESUMEN

This study investigates the absorption of the induced E-field in homogeneous biological tissue exposed to highly localized field sources in proximity of the body, such as the charged tips of antennas, where E-field coupling dominates. These conditions are relevant for compliance testing of modern mobile phones where exposure is evaluated at small separation between radiators and the body. We derive an approximation that characterizes the decay of the induced E-field in the tissue as a function of distance. The absorption is quantified in terms of the local specific absorption rate (SAR) at the tissue surface as a function of the charge at the antenna tip. The approximation is based on the analytical evaluation of the E-fields of a charged disk under quasi-static conditions. We validate this approximation using full-wave simulations of dipoles. We demonstrate that the coupling mechanism of the E-field is dominated by the perpendicular field component and that wave propagation need not be considered for the characterization of the exposure. The surface SAR decreases approximately with the fourth power of the distance and with the square of the ratio of the permittivities of the tissue and free-space. The approximation predicts the induced maximum E-field with an accuracy of better than 1.5 dB. © 2022 Bioelectromagnetics Society.


Asunto(s)
Teléfono Celular , Campos Electromagnéticos , Ondas de Radio
5.
Sensors (Basel) ; 22(16)2022 Aug 12.
Artículo en Inglés | MEDLINE | ID: mdl-36015794

RESUMEN

In agriculture, efforts are being made to reduce pesticides and fertilizers because of the possible negative environmental impacts, high costs, political requirements, and declining social acceptance. With precision farming, significant savings can be achieved by the site-specific application of fertilizers. In contrast to currently available single sensors and camera-based systems, arrays or line sensors provide a suitable spatial resolution without requiring complex signal processing and promise significant potential regarding price and precision. Such systems comprise a cost-effective and compact unit that can be extended to any working width by cascading into arrays. In this study, experiments were performed to evaluate the applicability of a TrueColor sensor array in monitoring the nitrogen supply of winter barley during its growth. This sensor is based on recording the reflectance values in various channels of the CIELab color space: luminosity, green-red, and blue-yellow. The unique selling point of this sensor is the detection of luminosity because only the CIELab color space provides this opportunity. Strong correlations were found between the different reflection channels and the nitrogen level (R² = 0.959), plant coverage (R² = 0.907), and fresh mass yield (R² = 0.866). The fast signal processing allows this sensor to meet stringent demands for the operating speed, spatial resolution, and price structure.


Asunto(s)
Hordeum , Nitrógeno , Agricultura , Fertilizantes , Nitrógeno/química , Estaciones del Año
6.
Nano Lett ; 21(1): 550-555, 2021 Jan 13.
Artículo en Inglés | MEDLINE | ID: mdl-33290080

RESUMEN

One particularly fascinating vision for charge-operated devices is the controlled assembly of structures from single surface-deposited molecules. Here, we report on the assembly of linear clusters that consist of phthalocyanine (H2Pc) molecules on a Ag(111) surface. The molecules are imaged as well as manipulated with a low-temperature scanning tunneling microscope (STM). Upon deprotonation of every second H2Pc, the resulting HPc molecule exhibits an isomeric bistability which can be used as inputs in logic gates. Combining our STM measurements with density functional theory calculations we show that the HPc isomers exhibit a repulsive electrostatic interaction with adjacent H2Pc molecules which, due to the asymmetric charge distribution on HPc, results in a counterclockwise or clockwise molecule tilt of the latter, thereby defining the logic 0 and 1 of the output. It is shown that information can be relayed along molecule chains over distances equivalent to at least nine molecules.

7.
Bioelectromagnetics ; 42(6): 484-490, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34130354

RESUMEN

The introduction of new dosimetric quantities, in particular, epithelial or absorbed power density for frequencies above 6 GHz, in exposure guidelines and safety standards requires the development of new experimental assessment procedures for compliance testing. In this study, we propose to approximate the peak spatial-average absorbed power density (psSab ) using the same measured data and algorithms that are used for determining the peak spatial-average specific absorption rate psSAR, which is currently limited to frequencies up to 10 GHz. The uncertainty component for the transformation of psSAR to psSab was evaluated as less than 0.55 dB (13.5%) for any source as close as 0.02 λ from the tissue simulating media. The approach is easy to implement and allows determining compliance with the basic restrictions of the latest safety guidelines. In the next project, we will expand dosimetric probes, phantoms, and procedures for frequencies above 10 GHz. © 2021 Bioelectromagnetics Society.


Asunto(s)
Campos Electromagnéticos , Radiometría , Algoritmos , Fantasmas de Imagen
8.
Bioelectromagnetics ; 42(7): 562-574, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34289515

RESUMEN

Several recent theoretical dosimetric studies above 6 GHz apply generic layered skin models. For this frequency range, new experimental phantoms for over-the-air performance of wireless devices were proposed that simulate the impedance matching effects of the stratum corneum layer (SCL) with a low-loss coating layer. The aim of this study was to verify the skin models by comparing their reflection coefficients S11 with measurements of 37 human volunteers (21 males, 16 females, 5-80 years) at 21 body locations (10 at palm, 11 at arm/face) with different SCL thicknesses, using waveguides covering frequencies from 40 to 110 GHz. Such measurements were also carried out with the phantom material. The statistical analysis showed strong evidence that S11 depends on the SCL thickness and no evidence that S11 depends on sex. The measured S11 values for thin and thick skin can be represented by SCL layers of 15 and 140 µm, respectively. These values correspond well to the assumptions of previous studies. (The cohort did not include volunteers doing heavy manual work.) The phantom material mimics the matching effect of the SCL with deviations from the waveguide measurements of less than 0.85 dB (22%), which confirms the suitability of layered phantoms to represent the electromagnetic reflection/absorption of human skin. © 2021 Bioelectromagnetics Society.


Asunto(s)
Fenómenos Electromagnéticos , Piel , Femenino , Humanos , Masculino , Modelos Teóricos , Fantasmas de Imagen , Radiometría
9.
Bioelectromagnetics ; 41(5): 348-359, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-32410291

RESUMEN

The most recent safety guidelines define basic restrictions for electromagnetic field exposure at frequencies more than 6 GHz in terms of spatial- and time-averaged transmitted power density inside the body. To enable easy-to-perform evaluations in situ, the reference levels for the incident power density were derived. In this study, we examined whether compliance with the reference levels always ensures compliance with basic restrictions. This was evaluated at several distances from different antennas (dipole, loop, slot, patch, and helix). Three power density definitions based on integration of the perpendicular real part of the Poynting vector, the real part of its three vector components, and its modulus were compared for averaging areas of λ2 /16, 4 cm2 (below 30 GHz) and 1 cm2 (30 GHz). In the reactive near-field (d < λ/(2π)), the transmitted power density can be underestimated if an antenna operates at the free space exposure limit. This underestimation may exceed 6 dB (4.0 times) and depends on the field source due to different coupling mechanisms. It is frequency-dependent for fixed-size averaging areas (4 and 1 cm2 ). At larger distances, transmission can be larger than the theoretical plane-wave transmission coefficient due to backscattering between the body and field source. Using the modulus of the incident Poynting vector yields the smallest underestimation. © 2020 Bioelectromagnetics Society.


Asunto(s)
Campos Electromagnéticos , Fenómenos Físicos , Análisis Espacio-Temporal
10.
Adv Physiol Educ ; 44(3): 423-429, 2020 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-32697155

RESUMEN

Functional understanding of the different parts of the cardiovascular system is essential for an insight into pathomechanisms of numerous diseases. During training cardiovascular physiology, students and early-stage medical personnel should understand the role of different functional parameters for systolic and diastolic blood pressure, as well as for blood flow. The impact of isolated parameters can only be studied in models. Here physical hydraulic models are an advantage in which the students have a direct contact to the mechanical properties of the circulatory system. But these models are often difficult to handle. The aim of the present study was to develop a comprehensive model of the cardiovascular system, including a mechanical heart with valves, an elastic aorta, a more rigid peripheral artery system, a total peripheral resistance, and a venous reservoir representing the variable cardiac preload. This model allows one to vary systematically several functional parameters and to continuously record their impact on pressure and flow. This model is embedded into a computer-based teaching system (LabTutor) in which the students are guided through the handling of the model (as well as the systematic variation of parameters), and the measured data can be analyzed. This hybrid teaching system, which is routinely integrated in physiology laboratory courses of medical students, allows students to work with a complex hydraulic model of the cardiovascular system and to analyze systematically the impact of influencing variables (e.g., increased peripheral resistance or changed cardiac preload) as well as pathophysiological dysfunctions (e.g., reduced aortic compliance).


Asunto(s)
Fisiología , Estudiantes de Medicina , Computadores , Hemodinámica , Humanos , Laboratorios , Modelos Cardiovasculares , Fisiología/educación , Enseñanza
11.
Am J Physiol Endocrinol Metab ; 317(6): E1081-E1093, 2019 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-31503512

RESUMEN

DPP-4 inhibitors, used for treatment of type 2 diabetes, act by increasing the concentrations of intact glucagon-like peptide-1 (GLP-1), but at the same time, they inhibit secretion of GLP-1, perhaps by a negative feedback mechanism. We hypothesized that GLP-1 secretion is feedback regulated by somatostatin (SS) from neighboring D-cells, and blocking this feedback circuit results in increased GLP-1 secretion. We used a wide range of experimental techniques, including gene expression analysis, immunohistochemical approaches, and the perfused mouse intestine to characterize the paracrine circuit controlling GLP-1 and SS. We show that 1) antagonizing the SS receptor (SSTr) 2 and SSTr5 led to increased GLP-1 and SS secretion in the mouse, 2) SS exhibits strong tonic inhibition of GLP-1 secretion preferentially through SSTr5, and 3) the secretion of S was GLP-1 receptor dependent. We conclude that SS is a tonic inhibitor of GLP-1 secretion, and interventions in the somatostain-GLP-1 paracrine loop lead to increased GLP-1 secretion.


Asunto(s)
Células Enteroendocrinas/metabolismo , Péptido 1 Similar al Glucagón/metabolismo , Receptor del Péptido 1 Similar al Glucagón/metabolismo , Mucosa Intestinal/metabolismo , Comunicación Paracrina , Células Secretoras de Somatostatina/metabolismo , Somatostatina/metabolismo , Animales , Inhibidores de la Dipeptidil-Peptidasa IV/farmacología , Células Enteroendocrinas/efectos de los fármacos , Péptido 1 Similar al Glucagón/efectos de los fármacos , Mucosa Intestinal/citología , Intestino Delgado/citología , Intestino Delgado/metabolismo , Intestinos , Ratones , Receptores de Somatostatina/antagonistas & inhibidores , Receptores de Somatostatina/metabolismo , Somatostatina/farmacología , Somatostatina-28/farmacología , Células Secretoras de Somatostatina/efectos de los fármacos
12.
Blood ; 130(21): 2307-2316, 2017 11 23.
Artículo en Inglés | MEDLINE | ID: mdl-28972011

RESUMEN

Pathogenic gain-of-function variants in the genes encoding phosphoinositide 3-kinase δ (PI3Kδ) lead to accumulation of transitional B cells and senescent T cells, lymphadenopathy, and immune deficiency (activated PI3Kδ syndrome [APDS]). Knowing the genetic etiology of APDS afforded us the opportunity to explore PI3Kδ inhibition as a precision-medicine therapy. Here, we report in vitro and in vivo effects of inhibiting PI3Kδ in APDS. Treatment with leniolisib (CDZ173), a selective PI3Kδ inhibitor, caused dose-dependent suppression of PI3Kδ pathway hyperactivation (measured as phosphorylation of AKT/S6) in cell lines ectopically expressing APDS-causative p110δ variants and in T-cell blasts derived from patients. A clinical trial with 6 APDS patients was conducted as a 12-week, open-label, multisite, within-subject, dose-escalation study of oral leniolisib to assess safety, pharmacokinetics, and effects on lymphoproliferation and immune dysregulation. Oral leniolisib led to a dose-dependent reduction in PI3K/AKT pathway activity assessed ex vivo and improved immune dysregulation. We observed normalization of circulating transitional and naive B cells, reduction in PD-1+CD4+ and senescent CD57+CD4- T cells, and decreases in elevated serum immunoglobulin M and inflammatory markers including interferon γ, tumor necrosis factor, CXCL13, and CXCL10 with leniolisib therapy. After 12 weeks of treatment, all patients showed amelioration of lymphoproliferation with lymph node sizes and spleen volumes reduced by 39% (mean; range, 26%-57%) and 40% (mean; range, 13%-65%), respectively. Thus, leniolisib was well tolerated and improved laboratory and clinical parameters in APDS, supporting the specific inhibition of PI3Kδ as a promising new targeted therapy in APDS and other diseases characterized by overactivation of the PI3Kδ pathway. This trial was registered at www.clinicaltrials.gov as #NCT02435173.


Asunto(s)
Fosfatidilinositol 3-Quinasa Clase I/antagonistas & inhibidores , Síndromes de Inmunodeficiencia/tratamiento farmacológico , Síndromes de Inmunodeficiencia/enzimología , Terapia Molecular Dirigida , Inhibidores de Proteínas Quinasas/farmacología , Piridinas/farmacología , Pirimidinas/farmacología , Animales , Quimiocinas/sangre , Niño , Preescolar , Fosfatidilinositol 3-Quinasa Clase I/inmunología , Fosfatidilinositol 3-Quinasa Clase I/metabolismo , Demografía , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Inmunoglobulina M/sangre , Síndromes de Inmunodeficiencia/inmunología , Síndromes de Inmunodeficiencia/patología , Lactante , Ganglios Linfáticos/efectos de los fármacos , Ganglios Linfáticos/patología , Activación de Linfocitos/efectos de los fármacos , Masculino , Mutación/genética , Tamaño de los Órganos , Fenotipo , Enfermedades de Inmunodeficiencia Primaria , Piridinas/farmacocinética , Pirimidinas/farmacocinética , Ratas , Bazo/efectos de los fármacos , Bazo/patología , Linfocitos T/efectos de los fármacos , Linfocitos T/inmunología , Serina-Treonina Quinasas TOR/antagonistas & inhibidores , Serina-Treonina Quinasas TOR/metabolismo , Transfección
13.
Eur J Clin Invest ; 48(10): e12999, 2018 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-30009473

RESUMEN

BACKGROUND: The early detection of acute kidney injury (AKI) in patients with chronic kidney disease (CKD) is an unmet clinical need. Proenkephalin (PENK) might improve the early detection of AKI. METHODS: One hundred and eleven hospitalized CKD patients undergoing radiographic contrast procedures were enrolled. PENK was measured in a blinded fashion at baseline (before contrast media administration) and on day 1 (after contrast media administration). The potential of PENK levels to predict contrast-induced AKI was the primary endpoint. RESULTS: Baseline creatinine and baseline PENK were similar in AKI and no-AKI patients. In AKI patients, day 1 PENK (198 pmol/L vs 121 pmol/L, P < 0.01) was significantly higher compared to no-AKI patients. The area under the curve (AUC) for the prediction of AKI by day 1 PENK was 0.79, 95% CI: 0.70-0.87, similar to serum creatinine: 0.78, 95% CI: 0.61-0.95. Delta PENK was significantly higher in AKI compared to no-AKI patients (53 pmol/L vs 1 pmol/L, P < 0.01). The AUC for the prediction of AKI by delta PENK was high (0.92, 95%CI 0.82-1.00) and remained high for creatinine-blind AKI (0.94, 95% CI: 0.87-0.97). CONCLUSION: Delta PENK levels improve the early detection of contrast-induced AKI in CKD patients over serial creatinine sampling. Delta PENK accelerates the detection of creatinine-blind AKI by 24 hours.


Asunto(s)
Lesión Renal Aguda/diagnóstico , Medios de Contraste/efectos adversos , Encefalinas/metabolismo , Precursores de Proteínas/metabolismo , Insuficiencia Renal Crónica/complicaciones , Lesión Renal Aguda/inducido químicamente , Anciano , Anciano de 80 o más Años , Área Bajo la Curva , Biomarcadores/metabolismo , Creatinina/metabolismo , Diagnóstico Precoz , Femenino , Hospitalización , Humanos , Soluciones Isotónicas/administración & dosificación , Masculino , Estudios Prospectivos , Bicarbonato de Sodio/administración & dosificación , Cloruro de Sodio/administración & dosificación
14.
Bioelectromagnetics ; 39(8): 617-630, 2018 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-30383885

RESUMEN

The objective of this paper is to determine a maximum averaging area for power density (PD) that limits the maximum temperature increase to a given threshold for frequencies above 6 GHz. This maximum area should be conservative for any transmitter at any distance >2 mm from the primary transmitting antennas or secondary field-generating sources. To derive a generically valid maximum averaging area, an analytical approximation for the peak temperature increase caused by localized exposure was derived. The results for a threshold value of 1 K temperature rise were validated against simulations of a series of sources composed of electrical and magnetic elements (dipoles, slots, patches, and arrays) that represented the spectrum of relevant transmitters. The validation was successful for frequencies in which the power deposition occurred superficially (i.e., >10 GHz). In conclusion, the averaging area for a PD limit of 10 W/m2 that conservatively limits the temperature increase in the skin to less than 1 K at any distance >2 mm from the transmitters is frequency dependent, increases with distance, and ranges from 3 cm2 at <10 GHz to 1.9 cm2 at 100 GHz. In the far-field, the area depends additionally on distance and the antenna array aperture. The correlation was found to be worse at lower frequencies (<10 GHz) and very close to the source, the systematic evaluation of which is part of another study to investigate the effect of different coupling mechanisms in the reactive near-field on the ratio of temperature increase to incident power density. The presented model can be directly applied to any other PD and temperature thresholds. Bioelectromagnetics. 39:617-630, 2018. © 2018 Wiley Periodicals, Inc.


Asunto(s)
Campos Electromagnéticos , Modelos Teóricos , Exposición a la Radiación/análisis , Humanos , Piel/efectos de la radiación , Temperatura
15.
Bioelectromagnetics ; 34(2): 104-13, 2013 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-23060256

RESUMEN

The radio frequency (RF) electromagnetic field of magnetic resonance (MR) scanners can result in significant tissue heating due to the RF coupling with the conducting parts of medical implants. The objective of this article is to evaluate the advantages and shortcomings of a new four-tier approach based on a combined numerical and experimental procedure, designed to demonstrate safety of implants during MR scans. To the authors' best knowledge, this is the first study analyzing this technique. The evaluation is performed for 1.5 T MR scanners using a generic model of a deep brain stimulator (DBS) with a straight lead and a helical lead. The results show that the approach is technically feasible and provides sound and conservative information about the potential heating of implants. We demonstrate that (1) applying optimized tools results in reasonable uncertainties for the overall evaluation; (2) each tier reduces the overestimation by several dB at the cost of more demanding evaluation steps; (3) the implant with the straight lead would cause local temperature increases larger than 18 °C at the RF exposure limit for the normal operating mode; (4) Tier 3 is not sufficient for the helical implant; and (5) Tier 4 might be too demanding to be performed for complex implants. We conclude with a suggestion for a procedure that follows the same concept but is between Tier 3 and 4. In addition, the evaluation of Tier 3 has shown consistency with current scan practice, namely, the resulting heat at the lead tip is less than 3.5 °C for the straight lead and 0.7 °C for the helix lead for scans at the current applied MR scan restrictions for deep brain stimulation at a head average SAR of 0.1 W/kg.


Asunto(s)
Estimulación Encefálica Profunda/efectos adversos , Imagen por Resonancia Magnética/efectos adversos , Prótesis e Implantes/efectos adversos , Ondas de Radio/efectos adversos , Encéfalo/efectos de la radiación , Simulación por Computador , Humanos , Masculino , Temperatura
16.
Eur Heart J ; 33(16): 2071-9, 2012 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-22267245

RESUMEN

AIMS: The most effective regimen for the prevention of contrast-induced nephropathy (CIN) remains uncertain. Our purpose was to compare two regimens of sodium bicarbonate with 24 h sodium chloride 0.9% infusion in the prevention of CIN. METHODS AND RESULTS: We performed a prospective, randomized trial between March 2005 and December 2009, including 258 consecutive patients with renal insufficiency undergoing intravascular contrast procedures. Patients were randomized to receive intravenous volume supplementation with either (A) sodium chloride 0.9% 1 mL/kg/h for at least 12h prior and after the procedure or (B) sodium bicarbonate (166 mEq/L) 3 mL/kg for 1 h before and 1 mL/kg/h for 6 h after the procedure or (C) sodium bicarbonate (166 mEq/L) 3 mL/kg over 20 min before the procedure plus sodium bicarbonate orally (500 mg per 10 kg). The primary endpoint was the change in estimated glomerular filtration rate (eGFR) within 48 h after contrast. Secondary endpoints included the development of CIN. The maximum change in eGFR was significantly greater in Group B compared with Group A {mean difference -3.9 [95% confidence interval (CI), -6.8 to -1] mL/min/1.73 m2, P = 0.009} and similar between groups C and B [mean difference 1.3 (95% CI, -1.7-4.3) mL/min/1.73 m(2), P = 0.39]. The incidence of CIN was significantly lower in Group A (1%) vs. Group B (9%, P = 0.02) and similar between Groups B and C (10%, P = 0.9). CONCLUSION: Volume supplementation with 24 h sodium chloride 0.9% is superior to sodium bicarbonate for the prevention of CIN. A short-term regimen with sodium bicarbonate is non-inferior to a 7 h regimen. ClinicalTrials.gov Identifier: NCT00130598.


Asunto(s)
Medios de Contraste/efectos adversos , Enfermedades Renales/prevención & control , Fármacos Renales/administración & dosificación , Bicarbonato de Sodio/administración & dosificación , Cloruro de Sodio/administración & dosificación , Administración Oral , Anciano , Anciano de 80 o más Años , Femenino , Tasa de Filtración Glomerular/efectos de los fármacos , Humanos , Infusiones Intravenosas , Enfermedades Renales/fisiopatología , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Resultado del Tratamiento
17.
Phys Med Biol ; 68(3)2023 01 20.
Artículo en Inglés | MEDLINE | ID: mdl-36595233

RESUMEN

Objective. Regulators require that wireless power transfer (WPT) systems and other strong magnetic field sources are compliant with the basic restrictions (BR) defined as the limits of the fields induced in the human body, i.e. the induced electric field/current density/specific absorption rate limits. This can be achieved by demonstrating compliance with the reference levels (RL) defined in air without the human body, i.e. the incident electric/magnetic field limits. Local sources, such as WPT transmitters, generate non-uniform fields that can locally exceed the RL while the induced fields are still well below the BR. In these cases, robust compliance with BR can be demonstrated, generally requiring a large number of simulations. In this study, we proposed an efficient evaluation using a homogeneous phantom and applying a coverage factor to account for the local field enhancements caused by the dielectric contrasts of the highly inhomogeneous human tissues.Approach. The generally applicable coverage factors were derived from a statistical analysis of the field enhancements observed on four magnetic near-field sources placed at different separation distances (2-80 mm) and locations on the back of 12 anatomical models. The field enhancements were characterized by the ratios between the peak induced fields in the anatomical models and those in the homogeneous half-space phantom (ϵr= 55,σ= 0.75 S m-1,ρ= 1,000 kg m-3) at the same distance.Main results. The resulting 99th percentile coverage factors range from 1 and 9 depending on the dosimetric quantity.Significance. The use of these coverage factors reduces the compliance testing effort from hundreds of simulations to only one, and makes experimental testing feasible without the support of simulations. The study also demonstrates that running only a few use-case simulations with anatomical models may underestimate the exposure by more than 10 dB.


Asunto(s)
Campos Electromagnéticos , Campos Magnéticos , Humanos , Radiometría , Electricidad , Fantasmas de Imagen
18.
Clin Transl Med ; 13(11): e1471, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37962000

RESUMEN

BACKGROUND: The NLRP3 inflammasome drives release of pro-inflammatory cytokines including interleukin (IL)-1ß and IL-18 and is a potential target for ulcerative colitis (UC). Selnoflast (RO7486967) is an orally active, potent, selective and reversible small molecule NLRP3 inhibitor. We conducted a randomized, placebo-controlled Phase 1b study to assess the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of selnoflast. METHODS: Nineteen adults with previous diagnosis of UC and current active moderate to severe disease were randomized 2:1 to selnoflast or placebo for 7 days. A dose of 450 mg QD (once daily) was selected to achieve 90% IL-1ß inhibition in plasma and colon tissue. Consecutive blood, sigmoid colon biopsies and stool samples were analyzed for a variety of PD markers. Safety and PK were also evaluated. RESULTS: Selnoflast was well-tolerated. Plasma concentrations increased rapidly after oral administration, reaching Tmax 1 h post-dose. Mean plasma concentrations stayed above the IL-1ß IC90 level throughout the dosing interval (mean Ctrough on Day 1 and Day 5: 2.55 µg/mL and 2.66 µg/mL, respectively). At steady state, post-dose selnoflast concentrations in sigmoid colon (5-20 µg/g) were above the IC90 . Production of IL-1ß was reduced in whole blood following ex vivo stimulation with lipopolysaccharide (LPS) (in the selnoflast arm). No changes were observed in plasma IL-18 levels. There were no meaningful differences in the expression of an IL-1-related gene signature in sigmoid colon tissue, and no differences in the expression of stool biomarkers. CONCLUSIONS: Selnoflast was safe and well-tolerated. Selnoflast 450 mg QD achieved plasma and tissue exposure predicted to maintain IL-1ß IC90 over the dosing interval. However, PD biomarker results showed no robust differences between treatment arms, suggesting no major therapeutic effects are to be expected in UC. The limitations of this study are its small sample size and indirect assessment of the effect on IL-1ß in tissue. TRIAL REGISTRATION: ISRCTN16847938.


Asunto(s)
Colitis Ulcerosa , Adulto , Humanos , Colitis Ulcerosa/tratamiento farmacológico , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Interleucina-18/uso terapéutico , Inflamasomas/metabolismo , Citocinas/metabolismo , Biomarcadores
19.
Bioelectromagnetics ; 33(5): 366-74, 2012 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-22105520

RESUMEN

The objective of this study was to investigate if persons with implantable medical devices are intrinsically protected by the current electromagnetic safety guidelines. For inter-laboratory comparisons, the U.S. Food and Drug Administration has defined a generic implant as consisting of an insulated wire with noninsulated tips, simulating active implants composed of a metallic case, and insulated wires with electric contacts at the tip. In this study, we determined the amplitude of the uniform electric fields induced in body tissues that cause a local increase in the tissue temperature by 1 °C in the presence of this generic implant for a wide range of frequencies and wire lengths. The field amplitudes were compared to the basic restrictions of the current exposure guidelines for both occupational and uncontrolled exposure. Results showed that a 1 °C temperature increase in the tissues around the tips of the generic implant can be reached for field strengths much smaller than 1% of those in the basic restrictions. The simulated results were validated by experimental evaluations. The impact of perfusion was investigated and was found to lead to a reduction in the local temperature peak by only 1.6-3 times. Additional simulations inside an inhomogeneous anatomical model were performed to ascertain whether similar heating as in the generic model was observed. The significant temperature elevations due to the presence of a generic implant indicate that demonstrating compliance with the basic restrictions might not be sufficient for persons with implants. Special considerations may be required, especially in the case of novel, emerging technologies that feature strong near-fields at frequencies below 10 MHz (e.g., wireless power-transfer systems).


Asunto(s)
Equipos y Suministros/efectos adversos , Guías como Asunto , Prótesis e Implantes/efectos adversos , Temperatura , Absorción , Campos Electromagnéticos/efectos adversos , Seguridad de Equipos/normas , Equipos y Suministros/normas , Humanos , Fantasmas de Imagen
20.
Bioelectromagnetics ; 33(8): 695-705, 2012 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-22674188

RESUMEN

We investigated whether domestic and professional induction cooktops comply with the basic restrictions defined by the International Commission on Non-Ionizing Radiation Protection (ICNIRP). Based on magnetic field measurements, a generic numerical model of an induction cooktop was derived in order to model user exposure. The current density induced in the user was simulated for various models and distances. We also determined the exposure of the fetus and of young children. While most measured cooktops comply with the public exposure limits at the distance specified by the International Electrotechnical Commission (standard IEC 62233), the majority exceeds them at closer distances, some of them even the occupational limits. The maximum current density in the tissue of the user significantly exceeds the basic restrictions for the general public, reaching the occupational level. The exposure of the brains of young children reaches the order of magnitude of the limits for the general public. For a generic worst-case cooktop compliant with the measurement standards, the current density exceeds the 1998 ICNIRP basic restrictions by up to 24 dB or a factor of 16. The brain tissue of young children can be overexposed by 6 dB or a factor of 2. The exposure of the tissue of the central nervous system of the fetus can exceed the limits for the general public if the mother is exposed at occupational levels. This demonstrates that the methodology for testing induction cooktops according to IEC 62233 contradicts the basic restrictions. This evaluation will be extended considering


Asunto(s)
Culinaria/instrumentación , Culinaria/normas , Exposición a Riesgos Ambientales/análisis , Exposición a Riesgos Ambientales/normas , Calefacción/instrumentación , Calefacción/normas , Vivienda , Adulto , Carga Corporal (Radioterapia) , Preescolar , Campos Electromagnéticos/efectos adversos , Femenino , Humanos , Masculino , Modelos Biológicos , Embarazo , Estándares de Referencia
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