Course of Cushing`s disease and treatment outcomes in correlation with pituitary MRI in children.

BACKGROUND: Cushing's disease (CD) is a rare disorder of a persistent cortisol excess caused by ACTH-secreting pituitary tumor (corticotropinoma). Transsphenoidal surgery (TSS) is a treatment of choice for СD, which effectiveness range is from 70 to 90%. Recurrence rate after successful treatment is about 25%. If surgical treatment is unsuccessful or recurrence appear, radiation treatment is the next therapeutic option, which effectiveness range is also 90%, but the hypopituitarism rate as side effect of treatment is higher. Preoperative predictors of remission and recurrence are still unexplored what leads to further investigations. AIM: Analysis of remission and recurrence rates of pediatric CD after successful treatment according to preoperative MRI and therapeutic option. MATERIALS AND METHODS: We conducted a retrospective analysis of 90 pediatric patients with CD who were observed between 1992 and 2020 at the Endocrinology Research Centre. RESULTS: The most common clinical symptoms of CD were weight gain [94%] and growth retardation [72%]. Pituitary tumor was detected on radiological imaging in 53/90 patients [59%], there were no signs of visible adenoma in 37/90 of patients [41%]. 63 of 90 patients underwent TSS (70%), 27 patients underwent radiosurgery (30%). Remission rate after TSS was 71% [45/63], after radiosurgery - 85% [23/27]. There were no significant differences in remission rates after radical treatment according to preoperative MRI results (P=0.21 after TSS and P=0.87 after radiosurgery, х2 analysis). Recurrence after successful treatment was diagnosed in 10 patients. There were no significant differences in time to recurrence according to preoperative MRI results (P=0.055, х2 analysis). Time to recurrence was statistically different after TSS compared to radiosurgery (P=0.007, Kaplan-Meier analysis) and in the group with developed adrenal insufficiency in the early postoperative period (P=0.04, Kaplan-Meier analysis). Analysis of side effect of treatment showed that the frequency of growth hormone and gonadotrophin deficiency was statistically higher after radiosurgery (р<0.01, Kruskel-Wallis ANOVA test). Diabetes insipidus was diagnosed only after TSS. CONCLUSION: Results of our study didn`t allow to use MRI-results as predictor of effectiveness treatment in pediatric CD. Therapeutic option has an impact on time to recurrence, not on recurrence rates. The frequency of growth hormone and gonadotrophin deficiency was statistically higher after radiosurgery compared to TSS. Further studies are needed to identify predictors of remission and recurrence in CD.>< 0.01, Kruskel-Wallis ANOVA test). Diabetes insipidus was diagnosed only after TSS. CONCLUSION: Results of our study didn`t allow to use MRI-results as predictor of effectiveness treatment in pediatric CD. Therapeutic option has an impact on time to recurrence, not on recurrence rates. The frequency of growth hormone and gonadotrophin deficiency was statistically higher after radiosurgery compared to TSS. Further studies are needed to identify predictors of remission and recurrence in CD.

[Clinical and radiological diagnosis of hypophysitis: a review of literature and own data].

This article presents a literature review of the various forms of hypophysitis, its varieties, as well as the problem of radiation diagnosis and treatment of this pathology. Hypophysitis is a poorly understood and multifactorial disease which the difficulty of diagnosing is not only to a variety of nonspecific clinical manifestations and hormonal research data, but also the ambiguous results of MRI studies, the lack of clear MR patterns. The article reflects the main histological types of hypophysitis, the peculiarities of diagnosis in connection with general clinical symptoms, outlines the features of each type of hypophysitis with their own clinical observations. This review is devoted to modern ideas about the clinical course of hypophysitis, presented a set of characteristic diagnostic signs of the disease according to MRI and the treatment algorithms recommended today are also highlighted. The article summarizes data from foreign literature and our own clinical observations in order to develop an optimal protocol for MRI studies in patients with suspected hypophysitis, to develop recommendations for radiologists and endocrinologists for the correct results interpretation. The uniqueness of this review is the lack of data on the clinic, diagnosis and treatment of hypophysitis in the Russian literature today.

Multimodal Optical Coherence Tomography for Intraoperative Evaluation of Tumor Margins and Surgical Margins in Breast-Conserving Surgery.

The aim of the study: We compare the effectiveness of multimodal optical coherence tomography (MM OCT) in the traditional structural OCT mode and the OCT elastography (OCE) mode in addressing two clinically important tasks: (1) detecting groups of tumor cells at surgical margins during breast-сonserving surgery (BСS) in breast cancer (BC) and (2) identifying breast tumor margins. The obtained results were correlated with corresponding histological sections. Materials and Methods: The study was performed on 100 surgical margin samples (top, bottom, medial, and lateral - four samples from each patient in total) obtained from 25 patients with BC who underwent BCS (lumpectomy), and on 25 postoperative tumor samples (to determine tumor margins). With MM OCT method, we visually and numerically assessed the scattering (level and depth of OCT signal penetration) and elastic (stiffness values, or Young's modulus (kPa)) properties of the tumor and non-tumor breast tissue and the obtained values were compared with the results of postoperative histological examination. Results: In 4 surgical margin samples (out of 100), with the OCE method we identified groups of histologically confirmed tumor cells ("positive" resection margins) at the distance of about 5 mm from the visible tumor margin. The identified zones were larger than 0.5 mm with stiffness of more than 400 kPa in all these cases. However, the structural OCT could not identify these groups of tumors and they were not distinguishable from the surrounding fibrous tissue.In the areas of tumor into non-tumor tissue transition, structural OCT images detected tumor margins only if they were adjacent to adipose tissue and did not detect them if there were adjacent to non-tumor fibrous tissue. OCE images with high stiffness values (more than 400 kPa) and high contrast showed a clear tumor margin with both adipose and fibrous tissue. Conclusion: The study demonstarets the potential of MM OCT, particularly its OCE mode, as a real-time method for intraoperative tumor margin and surgical margin assessment in BCS. OCE images compared to structural OCT images visualize higher contrast between different types of breast tissue (adipose tissue, fibrous stroma, hyalinized stroma, tumor cell clusters), as well as more accurate identification of the tumor border and detection of small groups of tumor cells at surgical margins. An algorithm for intraoperative MM OCT examination of the state of the resection margin is proposed in accordance with standard clinical guidelines for achieving clean surgical margins in breast cancer patients.

[Adrenal imaging: anatomy and pathology (literature review)].

This literature review focuses on the normal adrenal gland anatomy and typical imaging features necessary to evaluate benign and malignant lesions. In particular, adenoma, pheochromocytoma, metastases and adrenocortical carcinoma were discussed as some of the most common lesions. For this purpose, a review of relevant local and international literature sources up to January 2021 was conducted.In many cases, adrenal incidentalomas have distinctive features allowing characterization using noninvasive methods. It is possible to suspect a malignant nature and promptly refer the patient for the necessary invasive examinations in some cases. -Computed tomography, especially with intravenous contrast enhancement, is the primary imaging modality because it enables differential diagnosis. Magnetic resonance tomography remains a sensitive method in lesion detection and follow-up but is not very specific for determining the malignant potential. Positron emission computed tomography also remains an additional method and is used mainly for differential diagnosis of malignant tumors, detecting metastases and recurrences after surgical treatment. Ultrasound has a limited role but is nevertheless of great importance in the pediatric population, especially newborns. Promising techniques such as radiomics and dual-energy CT can expand imaging capabilities and improve diagnostic accuracy.Because adrenal lesions are often incidentally detected by imaging performed for other reasons, it is vital to interpret such findings correctly. This review should give the reader a broad overview of how different imaging modalities can evaluate adrenal pathology and guide radiologists and clinicians.

Fragility of surface states in topological superfluid 3He.

Superfluid 3He, with unconventional spin-triplet p-wave pairing, provides a model system for topological superconductors, which have attracted significant interest through potential applications in topologically protected quantum computing. In topological insulators and quantum Hall systems, the surface/edge states, arising from bulk-surface correspondence and the momentum space topology of the band structure, are robust. Here we demonstrate that in topological superfluids and superconductors the surface Andreev bound states, which depend on the momentum space topology of the emergent order parameter, are fragile with respect to the details of surface scattering. We confine superfluid 3He within a cavity of height D comparable to the Cooper pair diameter ξ0. We precisely determine the superfluid transition temperature Tc and the suppression of the superfluid energy gap, for different scattering conditions tuned in situ, and compare to the predictions of quasiclassical theory. We discover that surface magnetic scattering leads to unexpectedly large suppression of Tc, corresponding to an increased density of low energy bound states.

[Heart arrhythmias and conduction disorders in patients with acromegaly: the role of cardiac magnetic resonance imaging].

Cardiovascular complications including arrhythmias and cardiac conduction disorders are one of the main reasons of high mortality rate in acromegaly, while they have not been well explored. AIM: To estimate arrhythmias frequency in acromegaly, identify risk factors leading to the development of arrhythmia and cardiac conduction disorder, to determine the role of cardiac MRI in detecting structural and functional changes. MATERIALS AND METHODS: A single-center prospective cohort study, which included 461 patients (151 men and 310 women) with acromegaly, was conducted. All the patients underwent a standard medical examination, including hormonal blood test, electrocardiogram, echocardiography, electrocardiogram daily monitoring. 18 patients with arrhythmias (11 men and 7 women) had cardiac MRI with gadolinium-based contrast. RESULTS: The results of our research show high frequency of arrhythmias and cardiac conduction disorders in patients with acromegaly 42%. Most frequent kinds of arrhythmias and cardiac conduction disorders were sinus bradycardia 19.1% of the cases and conduction disorders of bundle branch blocks 14.5%. Men were more likely to suffer from arrhythmias and cardiac conduction disorders than women (54.2% and 37.4%, respectively,p=0.0005). Not acromegaly activity but duration of the disease was a main risk factor of arrhythmias and cardiac conduction disorders. Patients with arrhythmias had a long anamnesis of acromegaly (10 and 7 years, respectively, p=0.04). Meanwhile, cardiac conduction disorders were commonly observed in the patients who were treated with somatostatin analogs comparing to the patients who didnt undergo this therapy (50% and 38.6% respectively,p=0.004). We showed that 61% of patients with acromegaly and cardiac conduction disorders who underwent magnetic resonance imaging (MRI) had the signs of myocardial fibrosis. The value of the ejection fraction of the left ventricle according to MRI was higher than with echocardiography (p=0.04). CONCLUSION: Arrhythmias and cardiac conduction disorders are often observed in patients with acromegaly even with remission of the disease. High risk group need careful diagnostic and monitoring approaches. Cardiac MRI is the gold standard for visualization of structural and morphological changes in the heart. Use of cardiac MRI in acromegalic patients expands our understanding of arrhythmias and cardiac conduction disorders in this disease. There are no specific laboratory markers of diffuse myocardial fibrosis, and the role of myocardial fibrosis in the occurrence of cardiac arrhythmias and conduction disorders needs further studying.

[The formation of state institutions of health care and development of medical business in Russia in the second half of XVI century].

The article considers historical characteristics of process of origin and formation of the health care system in Russia as process of state organizational activities. The starting point of the mentioned process is determined the period of the second half of XVI century that initiated becoming of institutional foundations of the whole health care system in Russia establishing the priority of state power initiative in becoming and development of the given processes. The significant role of foreign factor in development of medicine business in Russia during the given historical period is emphasized. The role of English medical men in popularization of European practice of medical treatment at the Tsar's court and in becoming of state institutions of health care is specially emphasized. At that, the state character of formation of health care system in Russia is stressed and is considered as national feature related to paternalistic character of the state authority itself. The specific facts of history of becoming of national health care system are considered in the context of universal historical development. On the whole, the period of governing of the Russian Tsars of second half of XVI century - Ivan VI the Terrible, Fedor Ioannovich, Boris Godunov, - is considered as unconditionally positive one in the process of becoming of the state medicine in Russia.

Statistical analysis of homogeneous nucleation of metallic nanoparticles during gas-phase synthesis.

In this work, we set out to develop a model of gas-phase nucleation in a mixture of copper and argon atoms, which can be further used for analysing macro-systems. Processes occurring at the atomic level are described using coefficients obtained by statistical analysis of molecular dynamic (MD) data on interactions of metal clusters with metal and argon atoms. The MD simulation results are compared with those obtained using the proposed macroscopic model. It is found that the coefficients obtained by averaging the interaction data suitably represent the integral value of the heat of condensation, although result in the smoothing of the energy distribution functions of the clusters. Analysis of the evolution of the number of clusters has shown that the values of their increase rate were lower than those obtained by MD simulation. The conclusion is made, that in order to improve the precision of the developed gas-phase condensation model, it should be supplemented by cluster coagulation.

Broken translational symmetry at edges of high-temperature superconductors.

Flat bands of zero-energy states at the edges of quantum materials have a topological origin. However, their presence is energetically unfavorable. If there is a mechanism to shift the band to finite energies, a phase transition can occur. Here we study high-temperature superconductors hosting flat bands of midgap Andreev surface states. In a second-order phase transition at roughly a fifth of the superconducting transition temperature, time-reversal symmetry and continuous translational symmetry along the edge are spontaneously broken. In an external magnetic field, only translational symmetry is broken. We identify the order parameter as the superfluid momentum ps, that forms a planar vector field with defects, including edge sources and sinks. The critical points of the vector field satisfy a generalized Poincaré-Hopf theorem, relating the sum of Poincaré indices to the Euler characteristic of the system.

[COMPREHENSIVE ASSESSMENT OF THE HEMOSTASIS SYSTEM IN TEST-SUBJECTS IN EXPERIMENT "MARS-500"].

The paper is devoted to the hemostasis studies in the course of long-term (520 d) isolation in an airtight chamber. Measured parameters included activated partial thromboplastin time (APTT), international normalized ratio (INR), thrombin time (TT); concentrations of fibrinogen (FBG), plasminogen (PG), Willebrand factor (WF), tissue factor pathway inhibitor (TFPI), and tissue plasminogen activator (TPA), thrombomodulin (TM); activities of the coagulation cascade factors (II, V, VII, X, VIII, IX, XI, XII), antithrombin III (ATIII), protein C (PC), C1-inhibitor (C1), α2-antiplasmin (AP), TPA and TFPI. The investigation revealed a diversity of changes in the plasma fibrinogen concentration, slower blood coagulation in the intrinsic pathway and the final stage, and a relative rise in the activities of ATIII and PC-inhibited factors. The rest parameters showed different trends.

[INVESTIGATION OF BLOOD BIOCHEMICAL INDICES DURING BICYCLE ERGOMETRY].

Our investigations showed that physical work (bicycle ergometry) alters the biochemical status of male volunteers. On the 5th minute of bicycle endometry capillary blood looses significantly glucose and increases magnesium, phosphorus and particularly lactic acid. Creatine phosphokinase activity and trygliceride levels did not deviate much from baseline values. All the changes had a similar trend equally in the supine and sitting position. Therefore, biochemical investigations may complement essentially the physiological and neurophysiological tests of human adaptability to physical loads. The investigation utilized the dry chemistry technology of rapid biochemical diagnostics.

[Multiple endocrine neoplasia type 1 syndrome with three classical components and chiasm glioma: specific features of target organ lesions and a clinical observation].

The article briefly reviews the specific features of target-organ lesions in multiple endocrine neoplasia type 1 (MEN1) syndrome and a clinical case of genetically confirmed MEN1 syndrome in a young female patient. Despite the relative rarity of this disease, timely diagnosis, treatment and screening for its main components are very important for the overall prognosis of patients with MEN1 and their first-degree relatives who are MEN1 gene mutation carriers. The described case is noteworthy for a number of specific features. The authors could find no account of optic chiasm glioma within the framework of MEN1 in the literature. Moreover, therapy-resistant somatoprolactinoma engages attention, which points to its aggressive nature with pituitary adenoma that is not been clearly visualized on magnetic resonance imaging. Of interest is the order of detection of neoplasms, in particular the manifestation of hypoglycemic episodes as a sign of organic hyperinsulinism. which have been initially regarded as epileptic seizures, after the use of sustained-release somatostatin analogues for the treatment of acromegaly.

Using a neural network approach and time series data from an international monitoring station in the Yellow Sea for modeling marine ecosystems.

The international marine ecological safety monitoring demonstration station in the Yellow Sea was developed as a collaborative project between China and Russia. It is a nonprofit technical workstation designed as a facility for marine scientific research for public welfare. By undertaking long-term monitoring of the marine environment and automatic data collection, this station will provide valuable information for marine ecological protection and disaster prevention and reduction. The results of some initial research by scientists at the research station into predictive modeling of marine ecological environments and early warning are described in this paper. Marine ecological processes are influenced by many factors including hydrological and meteorological conditions, biological factors, and human activities. Consequently, it is very difficult to incorporate all these influences and their interactions in a deterministic or analysis model. A prediction model integrating a time series prediction approach with neural network nonlinear modeling is proposed for marine ecological parameters. The model explores the natural fluctuations in marine ecological parameters by learning from the latest observed data automatically, and then predicting future values of the parameter. The model is updated in a "rolling" fashion with new observed data from the monitoring station. Prediction experiments results showed that the neural network prediction model based on time series data is effective for marine ecological prediction and can be used for the development of early warning systems.

[Atypical clinical course of Cushing's disease].

Endogenous hypercorticism is a severe endocrine disease with clinical symptoms resulting from long-term action of corticosteroids. In this country, conditions caused by the excess pituitary ACTH production are called Itsenko-Cushing disease. In the absence of adequate treatment, half of the patients die within 5 years after the onset of the disease. Correct diagnosis prior to the development of severe complications significantly improves its prognosis and patients' quality of life. It is generally believed that endogenous hypercorticosm must be accompanied by pathognomonic symptoms that may be helpful in establishing the diagnosis. However, certain patients present with non-specific symptoms of little diagnostic value. We report a case of Itsenko-Cushing disease lacking in specific symptoms of hypercorticism.

[Dynamics of the protein content of human urine during 5-day immersion].

Variations in the protein spectrum (12 groups) of native daily urine were studied during 5-day dry immersion (DI) of 14 subjects at the age of 19 to 26 years using gradient electrophoresis in polyacrylamide gel. Protein excretion with urine did not alter in the course of the experiment. However, the urine proteins spectrum trended to some shifts. Excretion of low-molecular proteins decreased and of albumin increased pointing to remodulation of tubular reabsorption initiated by the experimental conditions. Steady growth of the Tamm-Horsfall protein concentration seems to be a defense reaction. There was an incremental decrease in immunoglobulins that could be associated with a reduction of glomerular filter permeability for high-molecular proteins.

Inactivation and mineralization of aerosol deposited model pathogenic microorganisms over TiO2 and Pt/TiO2.

Air disinfection from bacteria and viruses by means of photocatalytic oxidation is investigated with microorganisms loaded over photocatalysts' films from aerosols. Deposition method and equipment have been developed to load Mycobacterium smegmatis , Bacillus thuringiensis , vaccinia virus, and influenza A (H3N2) virus on slides with undoped TiO(2) and platinized sulfated TiO(2) (Pt/TiO(2)). Inactivation dynamics was measured under UVA irradiation and in the dark. About 90% inactivation is reached in 30 min irradiation on TiO(2) and from 90 to 99.8% on Pt/TiO(2). The first-order inactivation rate coefficient ranged from 0.18 to 0.03 min(-1), over Pt/TiO(2) being higher than on TiO(2) for all microorganisms except Bacillus thuringiensis. The photocatalytic mineralization of Bacillus thuringiensis was performed on TiO(2) and Pt/TiO(2) with different photocatalyst and microorganism loadings. Completeness of mineralization depended on the TiO(2) to bacteria mass ratio. The rate of the photocatalytic carbon dioxide production grows with both the cell mass increase and the photocatalyst mass increase. Pt/TiO(2) showed increased rate of mineralization as well as of the inactivation likely due to a better charge carrier separation in the doped semiconductor photocatalyst. The results demonstrate that photocatalytic filters with deposited TiO(2) or Pt/TiO(2) are able to inactivate aerosol microorganisms and completely decompose them into inorganic products and Pt/TiO(2) provides higher disinfection and mineralization rates.

Nodes versus minima in the energy gap of iron pnictide superconductors from field-induced anisotropy.

We develop the formalism for computing the oscillations of the specific heat and thermal transport under rotated magnetic field in multiband superconductors with anisotropic gap and apply it to iron-based materials. We show that these oscillations change sign at low temperatures and fields, which strongly influences the experimental conclusions about the gap structure. We find that recent measurements of the specific heat oscillations indicate that the iron-based superconductors possess an anisotropic gap with deep minima or nodes close to the line connecting electron and hole pockets. We predict the behavior of the thermal conductivity that will help distinguish between these cases.

Air detoxification with nanosize TiO2 aerosol tested on mice.

A method for fast air purification using high concentration aerosol of TiO(2) nanoparticles is evaluated in a model chemical catastrophe involving toxic vapors of diisopropyl fluorophosphate (DFP). Mice are used as human model in a closed 100 dm(3) chamber. Exposure of mice to 37 ppm of DFP vapor for 15 min resulted in acute poisoning. Spraying TiO(2) aerosol in 2 min after the start of exposure to DFP vapors resulted in quick removal of DFP vapors from the chamber's air. Animals did not show signs of poisoning after the decontamination experiment and exposure to TiO(2) aerosol alone. Reactive oxygen species (ROS) and antioxidant activity (AOA) of mice blood plasma were measured for animals exposed to sound of aerosol generator, DFP vapors, TiO(2) aerosol and DFP vapors+TiO(2) aerosol. Reduced ROS and increased AOA were found for mice exposure to sound, DFP and TiO(2) aerosol. Exposure to DFP and decontamination with TiO(2) nanoparticles resulted in decreased AOA in 48 h following the exposure. The results suggest that application of TiO(2) aerosol is a powerful method of air purification from toxic hydrolysable compounds with moderate health aftermaths and requires further study and optimization.