Surgical treatment of trophoblastic disease. Modern concept and contradictions (literature review)

A review of studies on the comparison of the effectiveness of surgical treatment of malignant trophoblastic tumors before the start of standard chemotherapy and in terms of combination treatment is presented. According to Russian and foreign studies, surgical treatment is relevant for patients with primary or metastatic tumor resistance. The article presents the results of treatment of patients after various types of operations. The most common volume of surgery was a hysterectomy. The article also discusses the results of treatment of benign forms of trophoblastic disease. Surgical treatment of a malignant trophoblastic tumor before the start of standard chemotherapy was performed according to vital indications or in connection with a tumor determined by imaging methods. And the analysis carried out in Blokhin National Medical Research Center of Oncology showed expected prognoses for patients who underwent surgical treatment prior to the start of standard chemotherapy regimens. Such patients were admitted to the clinic with a resistant or disseminated form of the tumor. During their treatment, high-dose chemotherapy or additional surgical interventions were required, which significantly worsened the prognosis of the disease. In the opposite case, when removing a localized resistant primary tumor or its metastasis, in the postoperative period, chemotherapy was not carried out in connection with marker remission

Highly Fluorinated Peptide Probes with Enhanced In Vivo Stability for 19^{19}F‐MRI

A labeling strategy for in vivo $^{19}$F-MRI (magnetic resonance imaging) based on highly fluorinated, short hydrophilic peptide probes, is developed. As dual-purpose probes, they are functionalized further by a fluorophore and an alkyne moiety for bioconjugation. High fluorination is achieved by three perfluoro-tert-butyl groups, introduced into asparagine analogues by chemically stable amide bond linkages. d-amino acids and β-alanine in the sequences endow the peptide probes with low cytotoxicity and high serum stability. This design also yielded unstructured peptides, rendering all 27 $^{19}$F substitutions chemically equivalent, giving rise to a single $^{19}$F-NMR resonance with <10 Hz linewidth. The resulting performance in $^{19}$F-MRI is demonstrated for six different peptide probes. Using fluorescence microscopy, these probes are found to exhibit high stability and long circulation times in living zebrafish embryos. Furthermore, the probes can be conjugated to bovine serum albumin with only amoderate increase in $^{19}$F-NMR linewidth to ≈30 Hz. Overall, these peptide probes are hence suitable for in vivo $^{19}$F-MRI applications

In Vivo Behavior of the Antibacterial Peptide Cyclo[RRRWFW], Explored Using a 3-Hydroxychromone-Derived Fluorescent Amino Acid

Labeling biomolecules with fluorescent labels is an established tool for structural, biochemical, and biophysical studies; however, it remains underused for small peptides. In this work, an amino acid bearing a 3-hydroxychromone fluorophore, 2-amino-3-(2-(furan-2-yl)-3-hydroxy-4-oxo-4H-chromen-6-yl)propanoic acid (FHC), was incorporated in a known hexameric antimicrobial peptide, cyclo[RRRWFW] (cWFW), in place of aromatic residues. Circular dichroism spectropolarimetry and antibacterial activity measurements demonstrated that the FHC residue perturbs the peptide structure depending on labeling position but does not modify the activity of cWFW significantly. FHC thus can be considered an adequate label for studies of the parent peptide. Several analytical and imaging techniques were used to establish the activity of the obtained labeled cWFW analogues toward animal cells and to study the behavior of the peptides in a multicellular organism. The 3-hydroxychromone fluorophore can undergo excited-state intramolecular proton transfer (ESIPT), resulting in double-band emission from its two tautomeric forms. This feature allowed us to get insights into conformational equilibria of the labeled peptides, localize the cWFW analogues in human cells (HeLa and HEK293) and zebrafish embryos, and assess the polarity of the local environment around the label by confocal fluorescence microscopy. We found that the labeled peptides efficiently penetrated cancerous cells and localized mainly in lipid-containing and/or other nonpolar subcellular compartments. In the zebrafish embryo, the peptides remained in the bloodstream upon injection into the cardinal vein, presumably adhering to lipoproteins and/or microvesicles. They did not diffuse into any tissue to a significant extent during the first 3 h after administration. This study demonstrated the utility of fluorescent labeling by double-emission labels to evaluate biologically active peptides as potential drug candidates in vivo

О верификации измерений скорости поверхностных течений когерентным радаром СВЧ-диапазона с помощью дрифтеров

Introduction. Conventional contact measurements of hydrographic parameters frequently fail to provide the necessary accuracy of data in the field of water area monitoring. This problem can be solved using coherent radars enabling direct measurements of surface current velocities.Aim. To establish the accuracy of surface current velocities measured by a Doppler radar using drifter data.Materials and methods. In June 2022, coastal operational oceanography studies were conducted at the hydrophysical test site of the Institute of Oceanology of the Russian Academy of Sciences in the Black Sea near Gelendzhik. Measurements were carried out using a coherent X-band radar installed on the Ashamba research vessel simultaneously with drifter experiments using Lagrangian drifters of the near-surface layer with an underwater 0.5 m sail. Coordinates were transmitted via mobile communication. The drifter data on the current velocity and direction were used to verify radar measurements. Measurements were taken onboard of the research vessel at a low speed and different distances from the shore, near the drifters. The tracks of the vessel and drifters were recorded simultaneously. Processing of the radar data involved obtaining Doppler spectra of signals to estimate the dynamic processes on the sea surface, including the current velocity.Results. Radial components of the near-surface current velocity were calculated. Then, the current velocity values obtained based on the drifter and radar data were compared.Conclusion. The present work makes a contribution to the advancement of methods for measuring surface currents from the board of a moving ship by Doppler radars. The obtained results confirm the suitability of the radar hardware and software and signal processing algorithms for measuring currents. The radar measurement data were found agree well with drifter data in the velocity range from 15 cm/s.Введение. Традиционные контактные средства измерений гидрографических параметров зачастую не обеспечивают необходимую оперативность получаемых данных для решения задач мониторинга акваторий. Перспективным направлением является применение когерентных радаров, позволяющих непосредственно измерять скорости поверхностных течений.Цель работы. Оценка достоверности результатов измерений приповерхностной скорости течения доплеровским радаром сравнением с данными дрифтеров.Материалы и методы. В июне 2022 г. был проведен эксперимент по прибрежной оперативной океанографии в Черном море на акватории гидрофизического полигона "Геленджик" Южного отделения Института океанологии РАН с использованием доплеровского радара. Скорость течения измерялась когерентизированным навигационным радиолокатором сантиметрового диапазона с цифровой обработкой, установленным на научноисследовательском судне "Ашамба", одновременно с дрифтерными экспериментами с использованием лагранжевых дрифтеров приповерхностного слоя с подводным парусом высотой 0.5 м, с передачей координат по мобильной связи. Данные дрифтеров о скорости и направлении течения использовались для верификации радарных измерений. Измерения проводились с борта научно-исследовательского судна на малом ходу на различном расстоянии от берега, вблизи дрифтеров. В процессе измерений осуществлялась запись треков судна и дрифтеров. Обработка данных радиолокатора основана на исследовании спектральных характеристик отраженного сигнала, позволяющих оценивать динамические процессы на морской поверхности.Результаты. По результатам обработки доплеровских спектров были получены радиальные составляющие скорости приповерхностных течений, далее было выполнено сопоставление скорости течений по данным дрифтеров и данным радиолокации.Заключение. Настоящая работа является определенным шагом в усовершенствовании методов измерений поверхностных течений с борта движущегося судна доплеровским радаром. Результаты верификации подтверждают пригодность аппаратно-программной части радара и алгоритмов обработки сигнала для измерения течений. Данные радиолокационных измерений хорошо согласуются с данными дрифтеров в диапазоне скоростей от 15 см/с

4-Dialkylamino-2,5-dihydroimidazol-1-oxyls with Functional Groups at the Position 2 and at the Exocyclic Nitrogen: The pH-Sensitive Spin Labels

Local acidity and electrostatic interactions are associated both with catalytic properties and the adsorption activity of various materials, and with the vital functions of biomolecules. The observation of acid–base equilibria in stable free radicals using EPR spectroscopy represents a convenient method for monitoring pH changes and the investigation of surface electrostatics, the advantages of which are especially evident in opaque and turbid samples and in porous materials such as xerogels. Imidazoline nitroxides are the most commonly used pH-sensitive spin probes and labels due to the high sensitivity of the parameters of the EPR spectra to pH changes, their small size, and their well-developed chemistry. In this work, several new derivatives of 4-(N,N-dialkylamino)-2,5-dihydrioimidazol-1-oxyl, with functional groups suitable for specific binding, were synthesized. The dependence of the parameters of their EPR spectra on pH was studied. Several showed a pKa close to 7.4, following the pH changes in a normal physiological range, and some demonstrated a monotonous change of the hyperfine coupling constant by 0.14 mT upon pH variation by four units

Effect of Sterical Shielding on the Redox Properties of Imidazoline and Imidazolidine Nitroxides

The oxidant properties of the series of 2,2,5,5-tetraalkyl imidazoline and imidazolidine nitroxides were investigated. An increase in the number of bulky alkyl substituents leads to a decrease in the rate of reduction with ascorbate, which makes the electrochemical reduction potential more negative and shifts the equilibrium in the mixture of nitroxide and reference hydroxylamine (3-carboxy-1-hydroxy-2,2,5,5-tetramethylpyrrolidine-1-oxyl-1-¹⁵N) toward the starting compounds. The effect of structural factors on these reactions was analyzed by means of multiple regression using the Fujita steric constant <i>E</i>_s and the inductive Hammett constant σ_I. Satisfactory statistical outputs were obtained in all of the biparameter correlations, denoting that the oxidant properties of the nitroxides are determined by steric and electronic effects of the substituents. The data imply that bulky substituents can stabilize nitroxide and/or destabilize hydroxylamine

Coastal Polynya Disrupts the Acoustic Backscatter Diurnal Signal Over the Eastern Laptev Sea Shelf

The diel vertical migration (DVM) of zooplankton is one of the largest species migrations to occur globally and is a key driver of regional ecosystems and the marine carbon pump. The dramatic changes in the Arctic environment in recent years, mainly associated with sea-ice decline, may have wide significance for the Arctic shelf ecosystems including DVM. Observations have revealed the occurrence of DVM in ice-covered Arctic waters, however, there have yet to be observations of DVM from the extensive Siberian shelves in the Eurasian Arctic and no analysis of how the sea-ice decline may affect DVM. Here, 2 yearlong time series of acoustic backscatter, collected by moored acoustic Doppler current profilers in the eastern Laptev Sea from August 1998 to August 1999, were used to examine the annual cycle of acoustic scattering, and therefore the annual cycle of DVM in the area. The acoustic time series were used along with atmospheric and oceanic reanalysis and satellite data. Our observations show that DVM did not occur during polar night and polar day, but is active during the spring and fall transition periods when there is a diurnal cycle in light conditions. DVM began beneath the fast ice at the end of polar night and increased in intensity through spring. However, the formation of a large polynya along the landfast ice edge in late March 1999 caused DVM to abruptly cease near the fast ice edge, while DVM persisted through spring to the start of polar day at the onshore mooring. We associate this cessation of synchronized DVM ∼1 month ahead of polar day with a predator-avoidance behavior of zooplankton in response to higher polar cod abundance near the polynya. During polar day, the intensity of acoustic scattering was attributed to the riverine suspended particles. Overall, our results highlight the occurrence of DVM on the Siberian shelves, the cessation of synchronized DVM when a polynya opens up nearby, and the potential impact of significant trends toward a more extensive Laptev Sea polynya as part of changing ice conditions in the Eurasian Arctic and their impact on the Arctic shelf ecology

Synthesis and Structural Analysis of Angular Monoprotected Diamines Based on Spiro[3.3]heptane Scaffold

The synthesis of all stereoisomers of spiro[3.3]­heptane-1,6-diamines suitably protected for use as building blocks in drug discovery is reported. Structural analysis revealed the similarity between the spiro[3.3]­heptane and cyclohexane scaffolds. Comparison of the distance between functional groups and their spatial orientation proved that (1<i>S</i>,4<i>r</i>,6<i>R</i>)- and (1<i>R</i>,4<i>r</i>,6<i>S</i>)-1,6-disubstituted spiro­[3.3]­heptanes can be considered as restricted surrogates of <i>cis</i>-1,4-disubstituted cyclohexane derivatives. Similarly, (1<i>S</i>,4<i>s</i>,6<i>R</i>)- and (1<i>R</i>,4<i>s</i>,6<i>S</i>)-1,6-disubstituted spiro[3.3]­heptanes are the restricted surrogates of <i>trans</i>-1,3-disubstituted cyclohexanes. Such replacement can be recommended for use in optimization of ADME parameters of lead compounds in drug discovery