Galina Diakova | University of Virginia (original) (raw)

Papers by Galina Diakova

BMC Gastroenterology, 2021

Background and aims Gastrointestinal manifestations in patients with COVID-19 are common but the ... more Background and aims Gastrointestinal manifestations in patients with COVID-19 are common but the role of endoscopy in this patient population remains unclear. We investigated the need for endoscopic procedures, their findings, and impact on patient care in a systematic and geographically diverse sample of patients hospitalized with COVID-19. Methods As part of the North American Alliance for the Study of Digestive Manifestations of COVID-19, we identified consecutive patients hospitalized with COVID-19 at 36 medical centers in the USA and Canada. We performed a secondary analysis of patients who underwent endoscopy, collecting information on endoscopic indications, findings, interventions, staffing, procedure location, anesthesia utilization, and adverse events. Results Data were collected on 1992 patients; 24 (1.2%) underwent 27 endoscopic procedures (18 upper endoscopies, 7 colonoscopies, 2 endoscopic retrograde cholangiopancreatographies). The most common indications were: gastro...

2018 IEEE International Ultrasonics Symposium (IUS), 2018

Remote monitoring of liposome payload release is of relevance to drug delivery and molecular imag... more Remote monitoring of liposome payload release is of relevance to drug delivery and molecular imaging. However, conventional methods of monitoring release (e.g. fluorescence dequenching, luciferase) are difficult to apply at depths> 5 mm in vivo. In this study, we evaluated the photoacoustic (PA) imaging response of a novel formulation of indocyanine-green (ICG) loaded liposomes. Specifically, we prepared two liposomes formulations of different mean diameter (180 nm vs 900 nm) and characterized the PA response before and after liposome destruction to determine if dye release resulted in a change in the PA response of the dye. Results indicated that dye loading efficiency was 90% in the 180 nm liposome formulation and 25% in the 900 nm formulation. When intact, both liposomes exhibited a narrow optical absorption peak centered near 780 nm that broadened and shifted to 750 nm following liposome rupture. This liposome preparation may be used as blood pool contrast agents, molecular i...

Digestive Diseases and Sciences

Background and Aims The most common symptoms of Covid-19 are respiratory; however, gastrointestin... more Background and Aims The most common symptoms of Covid-19 are respiratory; however, gastrointestinal symptoms are present in up to 50% of patients. We aimed to determine characteristics associated with the development of gastrointestinal symptoms in patients with Covid-19. Methods A case-control study of adults hospitalized for Covid-19 was conducted across a geographically diverse alliance of 36 US and Canadian medical centers. Data were manually abstracted from electronic health records and analyzed using regression analyses to determine characteristics associated with any gastrointestinal symptoms and diarrhea specifically. Results Of 1406 patients, 540 (38%) reported at least one gastrointestinal symptom and 346 (25%) reported diarrhea. Older patients (≥ 80 years) had significantly lower rates of any gastrointestinal symptoms and diarrhea (vs. patients 18-79 years, OR 0.41, p < 0.01 and OR 0.43 p = 0.01, respectively), while those with IBS (OR 7.70, p = 0.02 and OR 6.72, p < 0.01, respectively) and on immunosuppressive therapy (OR = 1.56, p = 0.02) had higher rates of any gastrointestinal symptom and diarrhea. Patients with constitutional symptoms exhibited significantly higher rates (OR 1.91, p < 0.01), while those with pulmonary disease alone had lower rates of gastrointestinal symptoms (OR 0.23, p = 0.01). A significant interaction between constitutional symptoms and pre-existing pulmonary conditions was observed. Conclusions Several patient-and disease-specific characteristics associate with gastrointestinal symptoms in patients with Covid-19. Knowledge of these may provide insights into associated pathophysiologic mechanisms, and help health care professionals provide targeted attention to reduce morbidity related to Covid-19. Keywords Covid-19 • Gastrointestinal symptoms • Characteristics Abbreviations ACE2 Angiotensin-converting enzyme 2 BMI Body mass index CI Confidence interval Covid-19 Coronavirus disease 2019 GLMM Generalized linear mixed models * Olga C. Aroniadis

Clinical Gastroenterology and Hepatology

Journal of Visualized Experiments

Journal of the Acoustical Society of America, 2016

Journal of Therapeutic Ultrasound, 2015

PURPOSE Targeted microbubbles are investigated as promising ultrasound molecular imaging agents. ... more PURPOSE Targeted microbubbles are investigated as promising ultrasound molecular imaging agents. A simple and efficient procedure for microbubble preparation and covalent attachment of targeting ligands is crucial for rapid translation to clinical use. METHOD AND MATERIALS Microbubbles were prepared by amalgamation in a sealed vial with perfluorobutane gas headspace and aqueous saline/propyleneglycol micellar dispersion of DSPC, PEG stearate and peptide-PEG-DSPE (1:1.1:0.2 mass ratio). For VCAM-1 targeting, VHPKQHRGGSK(FITC)GC-PEG3400-DSPE was synthesized by reacting C-terminal cysteine thiol with maleimide-PEG-DSPE. For the formulation of αVβ3 integrin-targeted bubbles, cycloRGDfK or control cycloRADfK were reacted with NHS-PEG3400-DSPE. In vitro microbubble targeting was investigated in a flow chamber (1 dyn/cm2) in an αVβ3-coated dish or albumin control. In vivo targeting was tested in a subcutaneous murine tumor model (C57BL/6, MC38, J. Schlom, NIH). Contrast ultrasound imaging ...

The Journal of Physical Chemistry B, 2009

The dynamics of water are critically important to the energies of interaction between proteins an... more The dynamics of water are critically important to the energies of interaction between proteins and substrates and determine the efficiency of transport at the interface. The magnetic field dependence of the nuclear spin-lattice relaxation rate constant 1/T 1 of water protons provides a direct characterization of water diffusional dynamics at the protein interface. We find that the surface-average translational correlation time is 30-40 ps and the magnetic field dependence of the water proton 1/T 1 is characteristic of two-dimensional diffusion of water in the protein interfacial region. The reduced dimensionality substantially increases the intermolecular re-encounter probability and the efficiency of the surface exploration by the small molecule, water in this case. We propose a comprehensive theory of the translational effects of a small diffusing particle confined in the vicinity of a spherical macromolecule as a function of the relative size of the two particles. We show that the change in the apparent dimensionality of the diffusive exploration is a general result of the small diffusing particle encountering a much larger particle that presents a diffusion barrier. Examination of the effects of the size of the confinement relative to the macromolecule size reveals that the reduced dimensionality characterizing the small-molecule diffusion persists to remarkably small radius ratios. The experimental results on several different proteins in solution support the proposed theoretical model, which may be generalized to other small-particle-large-body systems like vesicles and micelles.

The Journal of Physical Chemistry B, 2011

Immobilized proteins present a unique interface with water. The water translational diffusive mot... more Immobilized proteins present a unique interface with water. The water translational diffusive motions affect the high-frequency dynamics and the nuclear spin-lattice relaxation as with all surfaces; however, rare binding sites for water in protein systems add very low-frequency components to the dynamics spectrum. Water binding sites in protein systems are not identical, thus distributions of free energies and consequent dynamics are expected. (2)H(2)O spin-lattice relaxation rate measurements as a function of magnetic field strength characterize the local rotational fluctuations for protein-bound water molecules. The measurements are sensitive to dynamics down to the kilohertz range. To account for the data, we show that the extreme-values statistics of rare events, i.e., water dynamics in rare binding sites, implies an exponential distribution of activation energies for the strongest binding events. In turn, for an activated dynamical process, the exponential energy distribution leads to a Pareto distribution for the reorientational correlation times and a power law in the Larmor frequency for the (2)H(2)O spin-lattice relaxation rate constants at low field strengths. The most strongly held water molecules escape from rare binding sites in times on the order of microseconds, which interrupts the intramolecular correlations and causes a plateau in the spin-lattice relaxation rate at very low magnetic field strengths. We examine the magnetic relaxation dispersion (MRD) data using two simple but related models: a protein-bound environment for water characterized by a single potential well and a protein-bound environment characterized by a double potential well where the potential functions for the local motions of the bound-state water are of different depth. This analysis is applied to D(2)O deuterium spin-lattice relaxation on cross-linked albumin and lysozyme, which is dominated by the intramolecular relaxation driven by the dynamical modulation of the nuclear electric quadrupole coupling. We also separate the intramolecular from the intermolecular contribution to water proton spin-lattice relaxation by isotope dilution and show that the intramolecular proton data map onto the deuterium relaxation by a scale factor implied by the relative strength of the quadrupole and dipolar couplings. The temperature and pH dependence of the magnetic relaxation dispersion are complex and accounted for by changing only the weighting factors in a superposition of contributions from single-well and double-well contributions. These experiments show that the reorientational dynamics spectrum for water, in and on a protein, is characterized by a strongly asymmetric distribution with a long-time tail that extends at least to microseconds.

Magnetic Resonance in Medicine, 2012

The magnetic field dependence of the composite (1)H(2)O nuclear magnetic resonance signal T(1) wa... more The magnetic field dependence of the composite (1)H(2)O nuclear magnetic resonance signal T(1) was measured for excised samples of rat liver, muscle, and kidney over the field range from 0.7 to 7 T (35-300 MHz) with a nuclear magnetic resonance spectrometer using sample-shuttle methods. Based on extensive measurements on simpler component systems, the magnetic field dependence of T(1) of all tissues studied are readily fitted at Larmor frequencies above 1 MHz with a simple relaxation equation consisting of three contributions: a power law, A*ω(-0.60) related to the interaction of water with long-lived-protein binding sites, a logarithmic term B*τ(d) *log(1+1/(ωτ(d))(2)) related to water diffusion at macromolecular interfacial regions, and a constant term associated with the high frequency limit of water-spin-lattice relaxation. The parameters A and B include the concentration and surface area dependences respectively. The logarithmic diffusion term becomes significant at high magnetic fields and is consistent with rapid translational dynamics at macromolecular surfaces. The data are fitted well with translational correlation times of approximately 15 ps for human brain white matter, but with a B value three times larger than gray matter tissues. This analysis suggests that the water-surface translational correlation time is approximately three times longer than in gray matter.

Journal of Solution Chemistry, 2007

The paramagnetic contributions from dioxygen to solute proton spin-lattice relaxation rate consta... more The paramagnetic contributions from dioxygen to solute proton spin-lattice relaxation rate constants are reported for a series of aromatic hydrocarbons and drug molecule fragments, in order to examine the energetic factors for intermolecular exploration in solution. The measurements provide differences in local oxygen concentration at different sites on the solute molecule. The relaxation rate differences caused by steric factors are

Journal of Magnetic Resonance, 2011

The paramagnetic contributions to water-proton-spin-lattice relaxation rate constants in protein ... more The paramagnetic contributions to water-proton-spin-lattice relaxation rate constants in protein systems spin-labeled with nitroxide radicals were re-examined. As noted by others, the strength of the dipolar coupling between water protons and the protein-bound nitroxide radical often appears to be larger than physically reasonable when the relaxation is assumed to be controlled by 3-dimensional diffusive processes in the vicinity of the spin label. We examine the effects of the surface in biasing the diffusive exploration of the radical region and derive a relaxation model that incorporates 2-dimensional dynamics at the interfacial layer. However, we find that the local 2-dimensional dynamics changes the shape of the relaxation dispersion profile but does not necessarily reproduce the low-field relaxation efficiency found by experiment. We examine the contributions of long-range dipolar couplings between the paramagnetic center and protein-bound-water molecules and find that the contributions from these several long range couplings may be competitive with translational contributions because the correlation time for global rotation of the protein is approximately 1000 times longer than that for the diffusive motion of water at the interfacial region. As a result the electron-proton dipolar coupling to rare protein-bound-water-molecule protons may be significant for protein systems that accommodate longlived-water molecules. Although the estimate of local diffusion coefficients is not seriously compromised because it derives from the Larmor frequency dependence, these several contributions confound efforts to fit relaxation data quantitatively with unique models.

Journal of Magnetic Resonance, 2006

The interaction of molecular oxygen with derivatives of nitroxide EPR spin labels has been invest... more The interaction of molecular oxygen with derivatives of nitroxide EPR spin labels has been investigated using nuclear spin-relaxation spectroscopy in aqueous and nonaqueous solvents. The proton spin-lattice relaxation rate induced by oxygen provides a measure of the local concentration of oxygen, which we find is dependent on solvent. In water, the hydrophobic effect increases the local concentration of oxygen in the nonpolar portions of solute molecules. For nitroxides reduced to the hydroxylamine in aqueous solutions, we find that the local concentration of oxygen is approximately twice that associated with a free diffusion hard sphere limit, while in octane, this effect is absent. These results show that nitroxide based ESR oximetry may suffer a reference concentration shift of order a factor of two if the aqueous nitroxide spectrum or relaxation is used as the reference.

Journal of Magnetic Resonance, 2005

Metal ion complexes provide flexible paramagnetic centers that may be used to define intermolecul... more Metal ion complexes provide flexible paramagnetic centers that may be used to define intermolecular contacts in a variety of solution phase environments because both the charge and electronic relaxation properties of the complex may be varied. For most complex ions, there are several proton equilibria that may change the effective charge on the complex as a function of pH which in turn affects the efficacy of application for defining the electrostatic surfaces of co-solute molecules. We report here spectrophotometric and nuclear spin relaxation studies on aqueous solutions of chromium(III) complexes of EDTA, DTPA, and bis-amides of both. The effective charges available from these paramagnetic centers range from -3 to +1 and we report the pH ranges over which the effective charge is defined with confidence for application in magnetic relaxation experiments.