Search

Purpose: This study comparatively analyzed the morphology of eye tissues after laser exposure using the latest generation of transscleral laser techniques - micropulse transscleral cyclophotocoagulation (MP-TSCPC) and laser activation of scleral hydropermeability (LASH) - in an anatomical experiment., Material and Methods: The study used pulsed-periodic radiation of an Er-glass fiber laser (λ=1.56 μm) and radiation of a diode laser (λ=0.81 μm) in the micropulse mode. A comparative morphological evaluation of histological preparations of target scleral and ciliary body (CB) tissues was performed with the study of laser-induced changes occurring after LASH and MP-TSCPC., Results: The study of histological preparations obtained after MP-TSCPC and LASH did not reveal any noticeable signs of an inflammatory reaction or significant destructive changes. There were no signs of pronounced coagulative changes in the form of disorganization of connective and muscle tissue in the exposure area. At the same time, MP-TSCPC was accompanied by thinning and discontinuity of the CB pigment epithelium in the projection of its flat part and expansion of the gaps between the anterior connective tissue fibers fixing the CB to the sclera, which is likely a factor contributing to uveoscleral outflow. After LASH, in the irradiated areas at the level of the outer layers of the sclera (¾ of its thickness) located in the projection of the flat part of the ciliary body, multiple slit-like cavities and enlargements (stretching) of interfiber spaces were revealed with simultaneous compaction of the inner part of the sclera (¼ of its thickness)., Conclusion: The identified morphological changes may indicate certain differences in the mechanisms of intraocular pressure (IOP) reduction after MP-TSCPC and LASH. The results of this study suggest that the enhancement of uveoscleral outflow of intraocular fluid and the hypotensive effect after MP-TSCPC may be associated with laser-induced expansion of the interspaces between the anterior connective tissue fibers of the CB in the suprachoroidal space. With LASH, the possible mechanism of lowering IOP may be related rather to an increase in transscleral filtration due to the appearance of slit-like interfiber spaces in the sclera, caused by local contraction of scleral fibers in the area of laser exposure. The absence of pronounced destructive changes at the histological level indicates the gentle nature of both laser techniques and the possibility of expanding the indications for the use of LASH in the treatment of glaucoma, including at its earlier stages.

Purpose: To study the morphological features of regenerative processes in dynamics after dacryocystorinostomy (DCR) with the use of Mitomycin C (MMC)., Methods: The study includes 31 cases. All patients underwent endonasal endoscopic DCR. Group 1 included 16 cases who received MMC injections. Group 2 included 15 cases who were treated with MMC on collagen sponge into the area of formed anastomosis. Biopsies for histological examination were taken on the 2nd, 5th, 7th, 14th, 21st, 28th and 60th days after the surgery. The samples were subjected to histological examination., Results: Activated fibroblasts were detected in patients of group 2 on the 5th day after the surgery which became the main cellular elements by the 14th day, and incomplete fibroblast mitoses were observed in group 1 by the 14th day. On the 28th day after the surgery, the transformation of the extracellular matrix into loose connective tissue was determined in patients of group 2, while single cellular elements represented by fibroblasts were preserved in biopsies obtained from patients of group 1. By the 60th day after the surgery, the restoration of a full-fledged epithelial lining was observed in all specimens., Conclusion: With the injection of MMC, inhibition of collagenogenesis by depression of extracellular collagen matrix formation, production of abortive mitoses in cells and inhibition of maturation and transformation of fibroblasts occur. The regeneration process takes place after MMC injection under a relative decrease in fibroblast impact.

An essential requirement for single-cell RNA sequencing in cancer is the preparation of high-quality single-cell suspensions from the tumor tissue. In this work, various methods of dissociation of tumor biopsy specimens were analyzed and developed to obtain a cell suspension with at least 80% viability. It was found that the optimal conditions for sample preparation are mechanical dissociation followed by incubation with a collagenase/hyaluronidase mixture with addition of DNAase I for 60 min. Thus, we optimize the approach for preparing single-cell suspensions from the tumor biopsy tissue for single-cell RNA sequencing., (© 2023. Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: In case of chronic inflammatory diseases of the pelvic organs (CID) in women, it is advisable to use therapeutic physical factors that have a sanogenetic effect in rehabilitation treatment programs., Aim: To study the effectiveness of complex restorative treatment of patients with chronic salpingoophoritis with the consistent use of therapeutic physical factors., Material and Methods: The study included 96 patients with chronic salpingoophoritis at the age of 18 to 49 years. Two groups were formed by a simple sampling method: in the main group (MG/ n =44), against the background of standardized treatment in inpatient conditions, patients received intravaginal ultrasound therapy, in non-hospital settings - interference therapy; in the control group (CG/ n =41) - women received only standardized therapy. The criteria for the effectiveness of treatment were: determination of markers of pain and inflammation; ultrasound examination of the ovarian arteries with their Doppler measurements; assessment of quality of life criteria., Results: Comprehensive restorative treatment of patients with chronic salpingoophoritis with sequential use of curative physical factors (CPF), according to direct and long-term observations, provides a significant reduction in pain intensity ( p <0.01), inflammation ( p <0.01), peripheral blood flow ( p <0.01), physical and mental health ( p <0.01)., Conclusion: The implementation of a new developed method of restorative treatment of patients with chronic salpingoophoritis with sequential use of CPF provided a significant increase of 10-12% in the effectiveness of therapeutic measures in comparison with standardized therapy ( p <0.05-<0.01).

Introduction: At present it remains relevant to develop new rehabilitation technologies for patients with circulatory system diseases who have undergone a cardiac surgery to restore the functions of the cardiorespiratory system more quickly, improve physical and mental health, and prevent the development of the atherosclerotic process., Aim: To study the effectiveness and safety of the new rehabilitation technology for the inpatient stage of medical rehabilitation of patients with post-sternotomy syndrome after coronary artery bypass surgery (CABS) using high-tone therapy., Material and Methods: The study included 85 men (the average age was 56.8±2.46 years old) with post-sternotomy syndrome after CABS. They were divided into two groups by simple randomization: the first/main (42 patients) and the second/control (43 patients). The control group of the patients had a standard rehabilitation complex; the main group was additionally prescribed a high-tone therapy according to a local method. The immediate results of the treatment were assessed by the dynamics of the clinical picture, the six-minute walk test, respiratory function, echocardiography, the level of cytokines, C-reactive protein and natriuretic peptide (NT-proBNP); distant - by QOL endpoints (questionnaire MOS SF-36)., Results: The groups of the patients were comparable in all baseline parameters. After the course of the procedures in the main group of patients there were positive reliable ( p <0.05-0.001) shifts in clinical (pain, shortness of breath, general weakness), functional (forced expiratory vital capacity, forced expiratory volume1, effusion separation) and laboratory parameters (leukocytes, interleukin-2 and 10, NT-proBNP). The intergroup analysis of long-term results registered significant ( p <0.05) differences in the QOL of patients in the main group by subscales: the role of somatic problems, vitality and mental health. Compliance to the III stage of medical rehabilitation (outpatient/home) was noted with 95.2% of the patients in the first group and 93.0% in the second., Conclusion: The additional appointment of a high-tone therapy to the rehabilitation standard for the patients with post-sternotomy syndrome after CABS significantly improves the immediate and long-term results of the treatment (QOL) contributing to a more pronounced reverse development of inflammatory and edematous syndromes, an increase in physical activity and psychosomatic health. The absence of adverse reactions with all the patients indicates the safety of rehabilitation complexes.

Introduction: The phenomenon of therapeutic and prophylactic effect of natural mineral waters (MW) used to restore tissue tolerance to glucose and normalize basal insulin secretion in metabolic syndrome is well known. At the same time, the use of selenium-enriched MW is promising due to its multitarget action including participation in the regulation of the protein-synthesizing function of cells., Aim: To study the effect of internal course intake of selenium-modified mineral waters of different composition on bone mineral density after long-term diet-induced metabolic disorders in the experiment., Material and Methods: The study was carried out on outbred male white rats that were distributed into 3 control groups (CG) and 4 main groups (MG). In CG1 14 animals received laboratory food and drinking water; in CG2 14 animals were modeled for diet-induced metabolic disorders, and they were withdrawn from the experiment the day after the cancellation of the hypercaloric diet (180 days); after the cancellation of the hypercaloric diet 180 days later 14 animals with diet-induced metabolic disorders in CG3 had a standard diet (laboratory food and drinking water) for 30 days. In the experimental groups (EG), the animals similarly to CG3 were modeled diet-induced metabolic disorders, after the cancellation of the diet they had a standard diet and watering with MW. In MG1 18 animals were given MW1 (Essentuki-4); in MG2 19 animals had a course of MW1Se (Essentuki-4 enriched with selenium); in MG3 14 animals had a course of MW2 (Slavyanovskaya); in MG4 18 animals had a course of MB2Se (Slavyanovskaya enriched with selenium). The weight (body weight) of the animals was monitored monthly. Biochemical studies, densitometry and computed microtomography were used to determine the effectiveness of MW., Results: The characteristics of spongy bone tissue of femoral metaphysis of the rats of the control groups revealed disorders of varying degrees, but, despite this, the bone tissue structure of the examined vertebral bodies in animals without a hyper caloric diet (CG1) was preserved. The analysis of the study results demonstrated a significant effectiveness of selenium-enriched MW in regulating metabolic processes ( p <0.05- p <0.01), bone mineral density ( p <0.05), reduced bone resorption ( p <0.05), that is, the characteristics of spongy bone tissue of femoral metaphysis and vertebral bodies of animals showed a clear tendency to restore bone structure., Conclusion: The results of this study make it possible to predict an increase in the effectiveness of medical rehabilitation of patients with somatic diseases when selenium-enriched MW is included in the programmes.

Carbon nanomaterials endowed with significant luminescence have been synthesized for the first time from an abundant, highly localized waste, the wet pomace (WP), a semi-solid by-product of industrial olive oil production. Synthetic efforts were undertaken to outshine the photoluminescence (PL) of carbon nanoparticles through a systematic search of the best reaction conditions to convert the waste biomass, mainly consisting in holocellulose, lignin and proteins, into carbon dots (CDs) by hydrothermal carbonization processes. Blue-emitting CDs with high fluorescence quantum yields were obtained. Using a comprehensive set of spectroscopic tools (FTIR, Raman, XPS, and 1 H/ 13 C NMR) in combination with steady-state and time-resolved fluorescence spectroscopy, a rational depiction of WP-CDs structures and their PL properties was reached. WP-CDs show the up-conversion of PL capabilities and negligible cytotoxicity against two mammalian cell lines (L929 and HeLa). Both properties are excellent indicators for their prospective application in biological imaging, biosensing, and dynamic therapies driven by light.

This article puts forward arguments in favor of the necessity of conducting complex measurements of molecular transport coefficients that quantitatively determine the coefficients of dynamic viscosity, thermal diffusivity and molecular diffusion. The rheological studies have been carried out on the viscometers of two types: those with a rolling ball (HÖPPLER ® KF 3.2.), and those with a rotary one (Rheotest RN 4.1.). The thermophysical studies have been performed using the analyzer Hot Disk TPS 2500S. The measurements have been taken in the temperature range of 283 to 363 K. The concentration of dry substances has varied from 16.2 to 77.7% dry wt. An empirical equation for calculating the density of aqueous solutions of beet molasses has been obtained. The diagrams of the dependence of the dynamic viscosity on the shear rate in the range of 1 s -1 to 500 s -1 at different temperatures have been provided. The diagrams of the dependence of the coefficients of thermal conductivity and thermal diffusivity on the temperature and the concentration of dry substances have been presented, and empirical equations for their calculation have been obtained. The findings can be used for engineering calculations of hydrodynamic and heat-exchange processes in biotechnological equipment.

Purpose: To identify the possible cause of an inflammatory reaction to a Russian-manufactured palpebral implant made of gold in the long term after surgery, and to determine the clinical and morphological changes in the tissues of the upper eyelid when the presence of the implant caused the inflammatory reaction., Material and Methods: The results of 150 operations with placement of a palpebral implant were analyzed. In 12 cases, a nonspecific inflammatory reaction was revealed within 2 to 4 weeks after the operation, in 7 cases it necessitated explantation, in 5 cases the local long-term use of an ointment with a corticosteroid made it possible to avoid extrusion and explantation. Chemical microanalysis of the palpebral implant and fragments of the removed capsule was performed using scanning electron microscopy (SEM), as well as immunohistochemical (IHC), macro- and microscopic examination of the fragments of connective tissue capsule was carried out after removal of the palpebral implant., Results: The obtained data confirm the chemical purity of the implant, the absence of abnormal accumulation of metals in the tissues of the eyelid. IHC, macro- and microscopic examination of the presented fragments of the connective tissue capsule revealed signs characteristic of an inflammatory reaction to a foreign body., Conclusion: Further research is needed to establish the factors and predictors for the development of inflammatory reactions to a foreign body and, in particular, to gold.

The article presents the work of a multidisciplinary team of experts from various fields of medicine to optimize the «Questionnaire for assessing chronic pelvic pain and pelvic organ dysfunction (QCPPD) of the Ryzhikh National Medical Research Centre for Coloproctology» for use in clinical practice. The survey of respondents was conducted from June 28 to September 28, 2021. As a result of this survey, by repeatedly making edits and clarifications during communication with respondents, the final version was obtained, which allows assessing the patient's subjective sensations by the nature and localization of pelvic pain, sensitivity disorders and pelvic organ function. The main objective of this Questionnaire is to differentiate patients with neurogenic pain from a huge number of patients with chronic pelvic pain. This aspect will allow a more targeted approach to the diagnosis and pathogenetically justified treatment of patients, including after appropriate instrumental examinations. The work of a multidisciplinary team implies a higher degree of objectification and terminological accuracy of the Questionnaire under discussion. The presented version of the «Questionnaire for assessing chronic pelvic pain and pelvic organ dysfunction (QCPPD) of the Ryzhikh National Medical Research Centre for Coloproctology» will be primarily used in coloproctological patients with pelvic pain problems and anal incontinence and obstructive defecation. Further studies will be directed to the clinical evaluation of the results of the work carried out.

Objective: To evaluate the effect of the preventive course of drinking mineral water enriched with selenium on the processes of resistance to the damaging action of reversible occlusion of the anterior mesenteric artery based on the comparison of intestinal morphological changes in the experiment., Material and Methods: There has been modeled ischemic reperfusion injury of the intestinal wall according to H. Ikeda and co-authors using reversible occlusion of the anterior mesenteric artery with 33 outbred male rats. The rats were divided into four groups by block randomization: the 1 st group - intact animals ( n =7) - without an exposure; the control group - sham operated animals ( n =6); the group of comparison ( n =7) - with a model-operation; the experimental group ( n =11) - animals with a model operation that had courses of intragastric watering of bottled sulfate-chloride-hydrocarbonate-sodium low-mineralized (2.2 g/l) drinking mineral water «Psyzh» enriched with selenium. Biopsies of the small intestine were taken for histological examination., Results: Histological examination of the small intestine of experimental animals determines various degrees of severity of damage: on average, the animals of the experimental group on the scale of C.J. Chiu (1970) had the lowest degree of severity of pathological changes, the animals of the group of comparison - 1.4 times higher ( p =0.02). That is, the effect of a preventive course of mineral water «Psyzh» enriched with selenium was manifested in the formation of resistance to the damaging effect of reversible occlusion of the anterior mesenteric artery; in the presence of ischemic reperfusion damage to the intestinal wall, comparable in severity to changes with the animals without prevention, the most significant positive effect was realized in the containment of reactive changes., Conclusion: The effect of the preventive course of drinking mineral water «Psyzh» enriched with selenium manifested itself in the formation of resistance to the damaging effect of reversible occlusion of the anterior mesenteric artery, which is the basis for introducing this technique into clinical practice in order to prevent the development of reperfusion injuries of the intestine.

In this paper, we used an EEG system to monitor and analyze the cortical activity of children and adults at a sensor level during cognitive tasks in the form of a Schulte table. This complex cognitive task simultaneously involves several cognitive processes and systems: visual search, working memory, and mental arithmetic. We revealed that adults found numbers on average two times faster than children in the beginning. However, this difference diminished at the end of table completion to 1.8 times. In children, the EEG analysis revealed high parietal alpha-band power at the end of the task. This indicates the shift from procedural strategy to less demanding fact-retrieval. In adults, the frontal beta-band power increased at the end of the task. It reflects enhanced reliance on the top-down mechanisms, cognitive control, or attentional modulation rather than a change in arithmetic strategy. Finally, the alpha-band power of adults exceeded one of the children in the left hemisphere, providing potential evidence for the fact-retrieval strategy. Since the completion of the Schulte table involves a whole set of elementary cognitive functions, the obtained results were essential for developing passive brain-computer interfaces for monitoring and adjusting a human state in the process of learning and solving cognitive tasks of various types.

Lipid hydroperoxides are key mediators of diseases and cell death. In this work, the structural and dynamic perturbations induced by the hydroperoxidized POPC lipid (POPC-OOH) in fluid POPC membranes, at both 23 and 37 °C, were addressed using advanced small-angle X-ray scattering (SAXS) and fluorescence methodologies. Notably, SAXS reveals that the hydroperoxide group decreases the lipid bilayer bending rigidity. This alteration disfavors the bilayer stacking and increases the swelling in-between stacked bilayers. We further investigated the changes in the apolar/polar interface of hydroperoxide-containing membranes through time-resolved fluorescence/anisotropy experiments of the probe TMA-DPH and time-dependent fluorescence shifts of Laurdan. A shorter mean fluorescence lifetime for TMA-DPH was obtained in enriched POPC-OOH membranes, revealing a higher degree of hydration near the membrane interface. Moreover, a higher microviscosity near TMA-DPH and lower order are predicted for these oxidized membranes, at variance with the usual trend of variation of these two parameters. Finally, the complex relaxation process of Laurdan in pure POPC-OOH membranes also indicates a higher membrane hydration and viscosity in the close vicinity of the -OOH moiety. Altogether, our combined approach reveals that the hydroperoxide group promotes alterations in the membrane structure organization, namely, at the level of membrane order, viscosity, and bending rigidity.

Despite advances in diagnostics and therapy of non-small cell lung cancer (NSCLC), the problem of prognosis and prevention of tumor progression is still highly important. Even if NSCLC is diagnosed in the early stages, almost a quarter of patients develop relapse; most of them die from recurrent disease. A large number of different markers have been proposed to predict the risk of NSCLC progression; however, none of them are used in clinical practice. It is obvious that this situation is related to the economic and methodological complexity of the proposed markers and/or their insufficient efficiency due to a lack of effective study models and tumor heterogeneity. Another reason may be that potential markers are developed for NSCLC progression in general, which is represented by at least four pathogenetically-distinct processes: synchronous lymph node metastasis, local, regional, and distant recurrence. In this review, we summarize data from published literature on clinicopathological, genetic, and molecular factors associated with different types of NSCLC progression and emphasize challenges and approaches to developing prognostic factors. In conclusion, we highlight the importance of further studies to reveal molecular mechanisms of NSCLC progression and the need for differential analysis of markers of local, regional, and distant recurrences for disease prognosis., Competing Interests: The authors have no conflicts of interest to declare., (© Copyright by the Author(s). Published by Cell Physiol Biochem Press.)

One of the main reasons of failure of dacryocystorhinostomy (DCR) is cicatricial closure of the ostium. Finding a way to prevent this outcome remains one of the leading aims of research in dacryology. The effectiveness of the most widespread methods is often considered contradictory by various researchers. Pirfenidone is a small-molecule agent that demonstrated good antifibrotic effect and low toxicity in previous in vitro research. There haven't been any in vivo studies of its intraoperative use in DCR., Purpose - to determine the in vivo efficacy of pirfenidone in prevention of ostium cicatricial closure following dacryocystorhinostomy in an animal experiment., Material and Methods: The study was conducted on 18 Chinchilla rabbits. They were divided into 3 groups and each animal underwent modified dacryocystorhinostomy. On the final stage of surgery rabbits of group 1 were injected 1 ml of 0.15 mg/ml pirfenidone solution, rabbits of group 2 - 0.3 mg/ml pirfenidone solution. No injections were performed in group 3. Animals were terminated on days 7 (6 rabbits), 14 (6 rabbits) and 28 (6 rabbits) following surgery. Lacrimal stoma patency was evaluated in vivo by irrigation, and morphologically postmortem. Tissue samples obtained from the stoma area were examined histologically for signs of fibrosis., Results: Failure of dacryocystorhinostomy was observed in 4 out of 18 cases: all rabbits of group 3 terminated on days 14 and 28. The most pronounced morphological signs of fibrosis were also noted in group 3. No topical or systemic adverse effects of the medication were observed in groups 1 and 2., Conclusion: Pirfenidone demonstrated high antifibrotic efficacy and low toxicity in experimental dacrycystorhinostomy in rabbits. These results provide grounds for further research into the use of pirfenidone in dacrycystorhinostomy.

The article present a case report of orbital granulomatous inflammation after a retrobulbar injection of allogenous stem cells. Experimental treatment resulted in an orbital tumor that required surgical excision. Lymphogranulomatous inflammation with a secondary abscess was verified by morphological and immunohistochemical analyses. This case demonstrates the possible dangerous complications of the "off-label" therapy amid the rising popularity of stem cells treatment.

Application of terahertz (THz) radiation in novel non-invasive biomedical technologies has recently received considerable attention. However, experimental data about the safety of exposure to THz radiation for biological objects (including eye structures in vivo ) are limited. To our knowledge, the safety of THz reflectometry (frequency range of 0.30-0.40 THz) has not been closely examined in an animal model with subsequent morphological assessment of corneal tissues., Purpose: To assess the safety of pulsed THz radiation with various parameters (time, power, and frequency) for the cornea in a rabbit model., Material and Methods: The sample for the current study consisted of 18 Chinchilla rabbits (18 eyes). Corneal imaging and epithelial cell density before and after the exposure were evaluated using confocal laser scanning microscopy (CLSM). The histological study for objective assessment of the cornea state (day 1 and day 14) was performed after experiment termination., Results: Single and multiple exposures of laser radiation at a frequency below 0.1 THz and power density below 30 nW/cm 2 do not cause visible structural changes in any layers of the rabbit cornea. The results obtained in the long-term period showed insignificant reversible morphological changes only within the epithelium., Conclusion: The described parameters of terahertz and subterahertz radiation can be considered safe for assessing changes in corneal epithelium hydration level using non-invasive methods based on THz reflectometry.

Purpose: To evaluate the structure of vitreous body in asteroid hyalosis by low vacuum scanning electron microscopy., Material and Methods: The material of the study was samples of the vitreous body obtained from 7 patients aged from 62 to 72 years with vitreomacular traction syndrome during vitrectomy. In all cases, clinical manifestations of asteroid hyalosis (the presence of multiple point-like echo-positive inclusions) were identified during the preoperative examination. Samples for scanning electron microscopy and chemical microanalysis were prepared without using fixation elements, total dehydration, staining or centrifugation, and according to the so-called principle of bougienage, which consists in partial separation of fractions of the gel-like tissue with a stream of saline., Results: The conducted examinations made it possible to identify various types of local accumulations of mineral elements in the vitreous body in asteroid hyalosis - called asteroid bodies - that is, multiple complex rounded formations consisting of needle-shaped crystals of a radial fibrous structure., Conclusion: The developed algorithm, which includes intraoperative sampling of the vitreous body in conditions of its minimal hydration and a special technique for preparing samples for scanning electron microscopy and chemical microanalysis, provides the capability for the in vivo assessment of morphological changes in hyaloid elements of the vitreous body. With that, asteroid bodies can be considered as markers of the vitreous structures that are difficult to visualize.

Uterine adenosarcoma is an uncommon biphasic tumor with benign epithelial and malignant mesenchymal components, often presenting difficulties for morphological diagnosis. We describe 5 cases of adenosarcoma of the uterine corpus and cervix, and vaginal stump in patients aged 46-76 years. Clinical data, ultrasound results, morphological data, including immunohistochemical studies with antibodies to CD10, estrogen and progesterone receptors, desmin, smooth muscle actin, and Ki-67 are presented. Large polypoid mass of the epithelial-mesenchymal structure within the uterine cavity in women of peri - and postmenopausal age require the exclusion of malignancy of the mesenchymal component with searchig for diagnostic criteria - periglandular cuffing of the stromal cells and mitoses.

We performed a fMRI study during which 18 healthy subjects passively viewed abstract images and tried to name them. The images were geometric primitives, impossible images (Penrose images), and ambiguous images (Rorschach inkblots). Activation and deactivation areas were revealed for each task. The results of psychological assessment of ambiguity tolerance according to MSTAT-I inventory were used as regressors. Deactivation of the precuneus (Brodmann area 7) and neighboring structures (especially when observing geometric primitives and inventing names for them) and in the fronto-temporal areas was associated with high ambiguity tolerance. Similar links were observed for both activation and deactivation (depending on the certain contrast) of the occipito-cerebellar area.

Purpose: To conduct a morphological study of structural changes in the nasolacrimal duct in secondary acquired nasolacrimal duct obstruction (SALDO) as a result of treatment with radioiodine., Methods: Twenty patients (20 cases) were involved: 10 cases with secondary acquired nasolacrimal duct obstruction at Hasner's valve level due to the treatment with radioiodine (group 1) and 10 cases with primary acquired nasolacrimal duct obstruction (group 2). During surgery, a biopsy of nasolacrimal duct tissue from Hasner's valve area was taken. A morphological study was performed using semi-fine sections technique., Results: Patients of group 1 showed the following: desquamation of columnar epithelium, pinpoint ulceration of nasolacrimal duct wall, collapse of a significant part of the capillary bed, and absence of blood cells in their lumen. State of secretory cells of mucous glands varied from necrobiotic to the different stages of dystrophic, decreased lumens of acini with abundant microvesicles in cell cytoplasm were revealed. A specific sign noted in patients of group 2 was mixed inflammatory infiltration of the mucosa of the nasolacrimal duct. The picture corresponds to the exacerbation of a chronic inflammatory process., Conclusions: Changes revealed in patients of group 1 include desquamation of nasolacrimal duct epithelium, mucous gland lesion, and moderate fibrosis that indicate a probable primary character of the lesion. In patients of group 2, fibrotic changes were more significant and were due to a chronic inflammatory process. Thus, secondary acquired nasolacrimal duct obstruction after treatment with radioactive iodine has a specific pathogenesis and should be classified as a separate nosological form.

Tumor borders are one of the most significant characteristics of any tumor, including that of the skin., Purpose: To compare histological borders of periorbital skin tumors with their autofluorescence borders built from the analysis of non-induced protoporphyrin IX autofluorescence., Material and Methods: The study group included 8 patients with skin tumors of the eyelids, periorbital region, eyebrow and zygomatic regions aged 54-88 years. The tumors varied in size from 2 to 8 mm and all displayed signs of basal cell carcinoma (BCC). At admission, all the patients underwent non-induced autofluorescence diagnosis. The images were processed with the «CancerPlot» program. During radio excision, the autofluorescent border of each neoplasm was marked with a surgical incision of about 5 mm long and 2 mm deep., Results: Upon pathomorphological examination, solid BCC was identified in 7 cases. The remaining case was senile keratosis. All reference incisions were located in healthy tissues not farther than 1 mm from the tumor (or keratosis locus, correspondingly)., Conclusion: By the example of facial BCC, an evident correlation was established between histological borders of the tumor and its native (non-induced) protoporphyrin IX autofluorescence.

Purpose: To evaluate the efficiency of modified crosslinking (M-CXL) in the treatment of purulent keratitis (PK) and corneal ulcers, including ulcers of mixed etiology., Material and Methods: M-CXL method involves simultaneous performance of CXL and frequent instillations of anti-infective agents (one drop every 5 minutes for 1 hour). The study included 39 patients (41 eyes) with purulent corneal ulcers (PCU) of various origin. The main group consisted of 26 patients (27 eyes) who were treated with M-CXL in combination with active conservative therapy. In the control group (13 patients, 14 eyes) only active conservative management was used., Results: Complete suppression of the purulent process in the main group was achieved in 21 (77.8%) eyes after 32.6±10.66 days, in the control group - in 9 (64.3%) eyes in 52.4±16.6 days. Complete suppression of purulent keratitis was achieved in 100% of cases with bacterial keratitis, 83% of cases with fungal keratitis and 70.5% of cases with mixed keratitis. When purulent infiltration occupied the entire depth of the stroma but was limited in area (less than 6 mm), the efficiency of M-CXL decreased to 66.6%. The clinical effect of M-CXL was absent or insufficient when PK extended to the Descemet's membrane with an area of more than 7 mm., Conclusion: In 77.8% of cases, modified crosslinking has showed pronounced therapeutic effect - complete arrest of purulent corneal infiltration. Recovery time in the main group was 1.6 times shorter than in the control group ( p <0.05). Resorption of the purulent infiltration occupying all layers of the stroma up to the Descemet's membrane with extensive areas was not achieved, however the corneal melting and keratitis progression were stopped, which allowed planned therapeutic penetrating keratoplasty with a graft of smaller diameter to be performed.

A frequent reason for visiting an ophthalmologist for patients of working age is computer vision syndrome (CVS): statistics show that up to 90% of users of personal electronic computers (PCs) suffer from this disease. Therefore, the actual task of modern rehabilitation medicine and ophthalmology is the search for an effective and safe way to prevent and treat the CVS among employees of enterprises., The Purpose of This Study: Was a scientific justification, an assessment of the effectiveness and safety of the use of electroneurostimulation (ENS) of the cervical sympathetic ganglia in patients with CVS., Material and Methods: 120 patients with the syndrome observed on an outpatient basis were examined. Patients were divided into 3 groups using simple randomization method. The 1st group (the main group - MG) included 39 patients who, against the background of gymnastics of the oculomotor muscles and muscles of the shoulder girdle, used ENS on the area of the sympathetic ganglia; in the 2nd group (group of comparison - GoC) included 41 patients who strictly performed the same muscle gymnastics (after every 2 hours of work with the PC); Group 3 (control group - CG) consisted of 40 patients who took an ENS course of exposure in placebo mode. In the dynamics, the stock of relative accommodation, near heterophory, tear production, threshold electrical sensitivity of the retina, electrolability of the optic nerve, contrast sensitivity, reading speed, print speed and accuracy and the level of subjective asthenopia were evaluated., Results: Initially, groups of patients with CVS did not differ among themselves in any of the investigated parameters. After a course of procedures in the MG, in contrast to the other two (GoC and CG), statistically significant positive shifts were revealed in relation to the selected endpoints, reflecting the severity of asthenopia, sensorineural, accommodative and oculomotor functions of the visual analyzer, as well as ophthalmoergonomics. Of the side effects of the procedures were recorded: moderate drowsiness (in 4 patients), a feeling of heaviness of the head (in 1 patient) and an increase in blood pressure (BP) by more than 15% of the initial (in 1 patient). They disappeared on their own and did not require withdrawal of treatment. A patient who noted a single increase in blood pressure subsequently received therapy every other day. Redness of the skin of the neck in the area of application of the electrodes was found with the same frequency in MG and CG., Conclusion: The inclusion of ENS in the rehabilitation treatment of workers professionally using a personal computer significantly increases the effectiveness of therapeutic measures, which proves the appropriateness of applying the proposed technology in CVS. The therapeutic action of complex therapy is realized through the effect of the ENS on an important reflexogenic zone - the cervical sympathetic ganglia, the activation of which ensures the normalization of the central, peripheral and autonomic functioning of the visual analyzer. Analysis of the frequency of registration of side effects in patients of the three groups allows us to conclude that the technique is safe.

Palpebral eyelid weight implants are currently considered as the gold standard method for lagophthalmos correction. Manufactured from different precious metals, they have both benefits and drawbacks. The article presents the results of an experimental morphological study of biointegration of different eyelid weight implants used for correction of paralytic lagophthalmos., Purpose: To investigate biointegration properties of implants made of gold, platinum and platinum-gold alloy., Material and Methods: The study enrolled 4 Chinchilla rabbits (8 eyelids). Palpebral implants manufactured of gold, platinum and platinum-gold alloy were placed into the eyelids of the experimental animals. The morphological examination was performed 1 and 6 months after the implantation using paraffin sections., Results: Light microscopy revealed that the implant beds were surrounded by pronounced fibrovascular capsule of uneven thickness over the whole follow-up. The capsule formed after the placement of an implant made of gold and platinum alloy was more loose. However, the emerging connective tissue bridges of the capsule contributed to its immobilization in the tissues and lower risk of extrusion. No signs of an inflammatory and/or allergic reaction were observed in any of the cases., Conclusion: The obtained results show that implants made of a 90/10% platinum-gold alloy and 999.9 fine platinum have similar biointegration in terms of morphological features during 6 months of the follow-up period.

Introduction: Recently, hyaluronic acid gel (HAG) fillers were proposed as an effective alternative treatment option for surgical orbital volume augmentation. Several authors reported about long-standing effect of the filler., Purpose: To assess the features of HAG biodegradation after intraorbital injection in experimental environment., Material and Methods: In the course of the experiment, 7 chinchilla rabbits (14 eyes) received a single 1ml intraorbital HAG injection (Restylane SubQ, Galderma, Sweden) using a cannula. The animals' orbits were examined by ultrasound scan after the injection and at 1, 3, 6, 9, 12 and 18 months. The animals were subsequently sacrificed for morphological study of orbital tissue containing the HAG filler., Results: The HAG filler persisted in the orbit of experimental animals during the whole follow-up period. The volume of HAG depot and its density diminished gradually till the 18th month, after which the particles of HAG could still be detected with the morphological study and ultrasound., Conclusion: The HAG filler persisted in the orbit of experimental animals up to 18 months. Incomplete biodegradation explains the longstanding duration of the injection effect.

Mycobacterium tuberculosis (Mtb) is the etiological agent of tuberculosis. One-fourth of the global population is estimated to be infected with Mtb, accounting for ∼1.3 million deaths in 2017. As part of the immune response to Mtb infection, macrophages produce metabolites with the purpose of inhibiting or killing the bacterial cell. Itaconate is an abundant host metabolite thought to be both an antimicrobial agent and a modulator of the host inflammatory response. However, the exact mode of action of itaconate remains unclear. Here, we show that Mtb has an itaconate dissimilation pathway and that the last enzyme in this pathway, Rv2498c, also participates in l-leucine catabolism. Our results from phylogenetic analysis, in vitro enzymatic assays, X-ray crystallography, and in vivo Mtb experiments, identified Mtb Rv2498c as a bifunctional β-hydroxyacyl-CoA lyase and that deletion of the rv2498c gene from the Mtb genome resulted in attenuation in a mouse infection model. Altogether, this report describes an itaconate resistance mechanism in Mtb and an l-leucine catabolic pathway that proceeds via an unprecedented ( R )-3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) stereospecific route in nature., Competing Interests: The authors declare no conflict of interest., (Copyright © 2019 the Author(s). Published by PNAS.)

Moderate heating of such collagenous tissues as cornea and cartilages by infra-red laser (IR laser) irradiation is an emerging technology for nondestructive modification of the tissue shape and microstructure for a variety of applications in ophthalmology, otolaryngology and so on. Postirradiation high-resolution microscopic examination indicates the appearance of microscopic either spheroidal or crack-like narrow pores depending on the tissue type and irradiation regime. Such examinations usually require special tissue preparation (eg, staining, drying that affect microstructure themselves) and are mostly suitable for studying individual pores, whereas evaluation of their averaged parameters, especially in situ, is challenging. Here, we demonstrate the ability of optical coherence tomography (OCT) to visualize areas of pore initiation and evaluate their averaged properties by combining visualization of residual irradiation-induced tissue dilatation and evaluation of the accompanying Young-modulus reduction by OCT-based compressional elastography. We show that the averaged OCT-based data obtained in situ fairly well agree with the microscopic examination results. The results obtained develop the basis for effective and safe applications of novel nondestructive laser technologies of tissue modification in clinical practice. PICTURE: Elastographic OCT-based images of an excised rabbit eye cornea subjected to thermomechanical laser-assisted reshaping. Central panel shows resultant cumulative dilatation in cornea after moderate (~45-50°C) pulse-periodic heating by an IR laser together with distribution of the inverse Young modulus 1/E before (left) and after (right) IR irradiation. Significant modulus decrease in the center of irradiated region is caused by initiated micropores. Their parameters can be extracted by analyzing the elastographic images., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Objective: To investigate the impact of the nasal mucosa on the outcomes of dacryocystorhinostomy on the basis of morphologic findings., Material and Methods: The investigation enrolled 73 patients who had undergone endonasal endoscopic dacryocystorhinostomy. Nasal mucosal biopsies were intraoperatively taken from all the patients. The obtained samples were subjected to standard histological examination, as well as to immunohistochemical study using an anti-alpha-smooth muscle actin antibody. To determine the intensity of inflammation in the tissue sample, a chronic inflammation score was calculated. The cell elements positively stained with α-smooth muscle actin were estimated using a semi-automatic method. The patients were divided into groups in accordance with the outcome of surgical treatment after 6 months., Results: An unfavorable outcome of dacryocystorhinostomy was observed in 10 (13.7%) patients. The samples obtained from the patients showed a higher chronic inflammation score (8.33%) and a larger number of the cell elements positively stained with α-smooth muscle actin (6026.38±1944.29). The correlation between the outcome of surgical intervention and the quantitative characteristics of myofibroblasts was statistically significant (p<0.05)., Conclusion: These studies suggest that there is a direct correlation of the efficiency of endonasal endoscopic dacryocystorhinostomy with the presence and degree of chronic nasal mucosal inflammation at baseline.

Introduction: Eyelid tumors can be diagnosed using various diagnostic techniques. However, capability of existing methods for determining the type and margins of the tumor at the preoperative stage remains insufficiently studied., Purpose: To improve the noncontact infrared meibography technique and determine its diagnostic capabilities for studying structural changes in meibomian glands in malignant eyelid tumors of epithelial origin., Material and Methods: The study included 49 people (66 eyelids), among which 21 (21 eyelids) with malignant eyelid tumors, 11 - with benign eyelid tumors (11 eyelids), and 17 (34 eyelids) comprised the control group. The mean age of patients was 64.8±1.56 years. Meibomian glands of the lower eyelids were photographed in infrared light. Receiver-operating characteristic (ROC) curves were constructed to estimate the sensitivity and specificity of the method., Results: Modified meibography showed 100% sensitivity and 90% specificity in the differential diagnosis of malignant and benign eyelid tumors in 32 patients. Unlike other methods, the modified meibography technique can clarify the margins of tumor growth, which is considered when planning the resection volume., Conclusion: Modified meibography can indicate the margins of tumor invasion; it can be successfully used in the differential diagnostics of malignant eyelid tumors of epithelial origin and benign eyelid tumors.

Purpose: To investigate the toxic effects of frequent instillations of anti-infective solutions (antibiotic eye drops - 0.3 and 1.4% tobramycin, 0.5% levofloxacin and 0.5% moxifloxacin; antiseptic eye drops - 0.05% pyloxidine and 0.025% chlorhexidine; antifungal drug - 2 mg/ml fluconazole solution) on ocular tissues., Material and Methods: The study was conducted on 21 Wistar rats (42 eyes) using method of semi-fine sections., Results: The majority of antibiotics and antifungal agents do not cause toxic reactions in rats` eyes when instilled with frequent regimen with the exception of 'fortified' 1.4% tobramycin and pyloxidine solutions, which caused a decrease in corneal endothelial cells density and formation of fibrovascular tissue in the anterior chamber., Conclusion: Frequent instillations of antimicrobial drug solutions is a safe method for the treatment of purulent corneal ulcers and purulent keratitis. The exceptions were solutions of 'fortified' 1.4% tobramycin and piloxidine (vitabact).

Purpose: To compare the results of scanning electron microscopy studies of the surface of bone fragments of orbital lateral wall formed by mechanical and ultrasonic bone removal devices., Material and Methods: The surfaces of 7 bone fragments have been investigated after bony orbital decompression in patients with thyroid eye disease (TED). Electron microscopy of the bone relief was performed after exposure to an ultrasonic surgical system or a high-speed drill., Results: Electron microscopy revealed that relief of the bony surface within a compact substance after application of an ultrasonic aspirator had parallel grooves of the same type up to 100 μm in depth and 80-100 μm wide, with relatively smooth edges. In the area of impact on spongy substance the bone surface became more amorphous, rougher due to the exposure of cellular structures at different depths. High-speed drill used in the area of compact substance left monotonous, almost flat relief with individual compact conglomerates of bone 'dust'. Removal of thinned fragments of the compact substance of the specimen led to appearance of the cellular structure typical for a spongy substance., Conclusion: Data on features of the relief of the edges of bone 'window' obtained for the first time, as well as specifics of working in conditions of limited surgical access allowed the conclusion that modern ultrasonic bone aspiration is promising for deep lateral wall decompression and some other orbital interventions.

At present, installation of punctal plugs (tear duct occluders) draws attention of ophthalmologists, but this method of treating dry eye syndrome (DES) is not without complications. Considering the rise of DES occurrence - the tendency anticipated to continue - as well as expansion of indications for installation of tear duct occluders, their usage can be expected to rise. The article describes a relatively rare clinical case that involved intracanalicular migration of silicone punctal plug. A female patient of 36 years old sought medical help in Research Institute of Eye Diseases (Moscow) to treat a lump in the area of lower lacrimal punctum in the left eye that was growing in size; the lump had appeared around 2 months prior to the visit. Patient's medical history read that around 2 years ago she had a silicone occluder installed in the lower lacrimal punctum of the left eye. On examination, in the area of lower lacrimal punctum, a body with a nutrient vascular pedicle deriving from lower lacrimal duct could be found. The occluder was absent in the opening of the lacrimal punctum. A revision of lower tear duct cavity was performed to remove its contents. The body filling tear duct opening was removed with forceps. Substance was then sent for histological examination. Tear duct was scraped out, the silicone occluder removed and sent to laboratory for scanning electron microscopy. The patient had no complaints 6 months after the procedure. CONCLUSION: The study showed that the forming body was granuloma resulting from aseptic inflammation. Surface of the silicone occluder in retention of lacrimal pathways remained unchanged. Described surgical tactic is suitable for treating patients with intracanalicular punctal plug migration.

The phosphotriesterase homology protein (PHP) from Escherichia coli is a member of a family of proteins that is related to phosphotriestrase (PTE), a bacterial enzyme from cog1735 with unusual substrate specificity toward the hydrolysis of synthetic organic phosphates and phosphonates. PHP was cloned, purified to homogeneity, and functionally characterized. The three-dimensional structure of PHP was determined at a resolution of 1.84 Å with zinc and phosphate in the active site. The protein folds as a distorted (β/α) 8 -barrel and possesses a binuclear metal center in the active site. The catalytic function and substrate profile of PHP were investigated using a structure-guided approach that combined bioinformatics, computational docking, organic synthesis, and steady-state enzyme kinetics. PHP was found to catalyze the hydrolysis of phosphorylated glyceryl acetates. The best substrate was 1,2-diacetyl glycerol-3-phosphate with a k cat / K m of 4.9 × 10 3 M -1 s -1 . The presence of a phosphate group in the substrate was essential for enzymatic hydrolysis by the enzyme. It was surprising, however, to find that PHP was unable to hydrolyze any of the lactones tested as potential substrates, unlike most of the other enzymes from cog1735.

Ipilimumab, a monoclonal antibody that recognizes cytotoxic T lymphocyte antigen (CTLA)-4, was the first approved "checkpoint"-blocking anticancer therapy. In mouse tumor models, the response to antibodies against CTLA-4 depends entirely on expression of the Fcγ receptor (FcγR), which may facilitate antibody-dependent cellular phagocytosis, but the contribution of simple CTLA-4 blockade remains unknown. To understand the role of CTLA-4 blockade in the complete absence of Fc-dependent functions, we developed H11, a high-affinity alpaca heavy chain-only antibody fragment (VHH) against CTLA-4. The VHH H11 lacks an Fc portion, binds monovalently to CTLA-4, and inhibits interactions between CTLA-4 and its ligand by occluding the ligand-binding motif on CTLA-4 as shown crystallographically. We used H11 to visualize CTLA-4 expression in vivo using whole-animal immuno-PET, finding that surface-accessible CTLA-4 is largely confined to the tumor microenvironment. Despite this, H11-mediated CTLA-4 blockade has minimal effects on antitumor responses. Installation of the murine IgG2a constant region on H11 dramatically enhances its antitumor response. Coadministration of the monovalent H11 VHH blocks the efficacy of a full-sized therapeutic antibody. We were thus able to demonstrate that CTLA-4-binding antibodies require an Fc domain for antitumor effect., Competing Interests: The authors declare no conflict of interest., (Copyright © 2018 the Author(s). Published by PNAS.)

Background: The use of agonists of gonadotropin-releasing hormone (GnRH) for the rehabilitation treatment of the patients presenting with endometriosis genitalis externa is known to significantly enhance the risk of development of hypoestrogenism. The so-called 'add-back-therapy' is carried out as a preventive measure to eliminate hypoestrogenism caused by the intake of GnRH agonists without detriment to the effectiveness of anti-hormonal therapy., Aim: The objective of the present study was to estimate the effectiveness of the new method ('add-back hormone replacement therapy') in comparison with anti-hormonal therapy with the use of GRH agonists at the stage of the early postoperative medical rehabilitation based on the drinking of mineral waters (MW) and radon therapy (RT) in the patients who had undergone the laparoscopic interventions for the treatment of endometrioid heterotopies of the ovaries (1-3 months post-operatively)., Material and Methods: To evaluate the effectiveness of the spa and health resort-based rehabilitation measures, the long-term effects of GnRH agonists have been studied in 2 groups of the patients formed by the of simple randomization method. The main group (MG) was comprised of 45 women received medical rehabilitation under conditions of a spa and health resort setting with the application of medium-salt water from the Pyatigorsk spring and radon therapy in the combination with triptorelin. The group of comparison (CG) was composed of 44 women given the treatment with the use of triptorelin under the out-patient conditions. The assessment of the results of the study included: the estimation of the intensity of pelvic pain syndrome, indicators of the hormonal status and the quality of life (QL), ultrasonic examination of the pelvic organs, and the occurrence of adverse effects of triptorelin. The duration of the study was 3 years (2014-2016)., Results: The analysis of the long-term results of the rehabilitative treatment has demonstrated that the rehabilitation activities under the spa and health resort conditions within 1-3 months after the surgical intervention including the application of MW and RT in the combination with an agonist of gonadotropin-releasing hormone (triptorelin) greatly contributed to the stability of the results of the treatment: specifically, only 2.5% of the patients suffered the recurrence of cystic ovarian endometriosis whereas 24.5% (p<0.001) reported the restoration of the reproductive function. The patients comprising the control group experienced the recurrence of the pathologic process in 7.5% of the cases and the restoration of the reproductive function in 15.8% of the cases (p<0.001). Simultaneously, the quality of life in the patients in the main group improved 3.4 times on the average in comparison with the initial level (p<0.001). The 2.2-fold improvement of the quality of life was documented in the control patients (p<0.001). At the same time, the frequency of adverse reactions to the treatment with triptorelin in the control patients was higher than in the main group including pain in the epigastric area, headache, irritability, hyperhidrosis, and instability of arterial blood pressure (ABP) that significantly deteriorated the life quality in these women., Conclusion: The comparative analysis of the results of the follow-up observations has demonstrated that the application of drinking mineral water and radon therapy for the treatment of the women suffering from endometriosis genitalis externa can be recommended as 'add-back therapy' against the background of anti-hormonal effects of agonists of gonadotropin-releasing hormone.

Despite the considerable achievements in the field of gastroenterology, there is still high incidence of diseases of the organs of the hepatobiliary system which necessitates the development of new therapeutic techniques for their management. Nowadays, high-intensity pulsed magnetic therapy is considered to be a highly efficacious method characterized by well-pronounced and many-sided action on the processes proceeding in the organism as a new preformed factor producing neurostimulatory, vasodilatory, trophic, and hypoalgesic effects. It appears to be effective with respect to biliary sludge (BS) since it can promote depletion of stagnant contents of the gall bladder and also intensify its contractile function., Aim: The objective of the present study was to evaluate the effectiveness of the application of the high-intensity pulsed magnetic field in the combination with the intake of mineral water (MW) and rational pharmacotherapy as the components of the combined treatment of biliary sludge., Methods: The study included 117 patients presenting with biliary sludge (BS) who were randomly allocated to three groups. Group 1 was comprised of 38 patients and served as the control group. These patients received medicamentous therapy (hymecromone - 200 mg 3 times daily during two weeks and ursodeoxycholic acid at a dose of 10-15 mg/kg a day during a period from 3 to 6 months). The second group consisted of 40 patients and served as the group of comparison. The patients of this group received medicamentous therapy in the combination with the intake of 'Sernovodskaya' hydrocarbonate-chloride-sulphate sodium mineral water (from a spring in the Chechen republic). The third group was composed of 39 patients and constituted the main study group. These patients completed a course of therapy with the use of the high-intensity pulsed magnetic field applied to the gall bladder region. Each patient underwent 10 sessions of magnetic therapy after the completion of the treatment with hymecromone and 'Sernovodskaya' mineral water. The treatment was carried out with simultaneous monitoring dynamics of the clinical symptoms of biliary sludge, the ultrasound examination of the abdominal organs with the evaluation of the contractile function of the gall bladder, the level of bilirubin in the cystic bile, bile acids, cholesterol, and cholate-cholesteric coefficient., Results: The combined treatment of the patients suffering from BS including the application of the high-intensity pulsed magnetic field alleviated the clinical symptoms of the disease much faster than medicamentous therapy combined with the intake of 'Sernovodskaya' mineral water. Moreover, it promoted the restoration of the motor activity of the gall bladder and accelerated the evacuation of the hyperechoic particles., Conclusion: The course of the combined treatment of the patients presenting with biliary sludge including the application of the high-intensity pulsed magnetic field in the combination with the intake of mineral water (MW) and rational pharmacotherapy significantly relieved abdominal pains, alleviated the symptoms of biliary dyspepsia, and improved the motor function of the biliary tract. These therapeutic effects persisted as long as 3 months. The results of the present study give evidence of the necessity of prescription of an optimum dose of ursodeoxycholic acid to the patients suffering from biliary sludge.

Purpose: To study the antifibrotic effectiveness of mitomycin-C in the tissues of the ostium site after it application for endonasal endoscopic dacryocystorhinostomy., Material and Methods: The study included 45 patients (48 cases) with primary obstruction of the nasolacrimal duct. All patients underwent endoscopic endonasal dacryocystorhinostomy (EEDCR). At the final stage of the operation, a swab with MMC was placed in the region of the formed ostium at a concentration of 0.2 mg/ml for 3 min. An ostium was not intubated. After that, biopsies of the mucous of the nasal cavity and lacrimal sac were performed to study the morphological changes that occur in the tissues overtime, as well as to calculate the concentration of the drug in the tissues., Results: According to the chemical analysis, the concentration of MMC immediately after application was 0.626 ± 0.176 μg/g; after 30 min the concentration of the drug was reduced to 0.23 ± 0.06 μg/g; a day after the operation the drug was not found in the tissue samples. Morphological study established that the repair processes occurring in the mucosa of the nasal cavity and the lacrimal sac after EEDCR are similar to the reparative processes without the use of MMC. The effectiveness of surgical treatment: "positive results" - 77.1% of cases, "relapses" - 22.9% of cases., Conclusions: Application of MMC for prevention of excessive scarring after EEDCR is impractical as it is not possible to achieve antifibrotic concentration of the drug at dacryocystorhinostomy ostium site using this method.

Single-wavelength anomalous dispersion (SAD) utilizing anomalous signal from native S atoms, or other atoms with Z ≤ 20, generally requires highly redundant data collected using relatively long-wavelength X-rays. Here, the results from two proteins are presented where the anomalous signal from serendipitously acquired surface-bound Ca atoms with an anomalous data multiplicity of around 10 was utilized to drive de novo structure determination. In both cases, the Ca atoms were acquired from the crystallization solution, and the data-collection strategy was not optimized to exploit the anomalous signal from these scatterers. The X-ray data were collected at 0.98 Å wavelength in one case and at 1.74 Å in the other (the wavelength was optimized for sulfur, but the anomalous signal from calcium was exploited for structure solution). Similarly, using a test case, it is shown that data collected at ∼1.0 Å wavelength, where the f'' value for sulfur is 0.28 e, are sufficient for structure determination using intrinsic S atoms from a strongly diffracting crystal. Interestingly, it was also observed that SHELXD was capable of generating a substructure solution from high-exposure data with a completeness of 70% for low-resolution reflections extending to 3.5 Å resolution with relatively low anomalous multiplicity. Considering the fact that many crystallization conditions contain anomalous scatterers such as Cl, Ca, Mn etc., checking for the presence of fortuitous anomalous signal in data from well diffracting crystals could prove useful in either determining the structure de novo or in accurately assigning surface-bound atoms.

The course of the real-time polymerase chain reaction (PCR) is determined by the temperature dependence of the kinetics of the component reactions, particularly the DNA strand hybridization. To investigate the effect of thermal processes on the reaction behavior, a mathematical model in which the variable rate constant of dissociation of "primer-single strand" complexes depends on temperature was proposed. The reaction medium temperature, which depends on time, was also introduced into the model. The proposed model of real-time PCR makes it possible to analyze different aspects of the reaction, which are important for the development of instruments and reagents for PCR.

A new method has been developed for the treatment of severe forms of keratoconjunctivitis sicca (KCS) that involves the use of an original cyclosporine A (CyA) saturated soft contact lens (SCL) together with preservative-free artificial tears therapy., Aim: to evaluate the effectiveness of the newly developed treatment for KCS based on the use of medical SCL saturated with 0.05% CyA., Material and Methods: The patients (43 men, 60 eyes) with severe KCS were divided into 2 groups. Group 1 included 21 patients (30 eyes), who received artificial tears and wore 0.05% CyA-saturated silicone-hydrogel SCLs. Group 2 included 22 patients (30 eyes), who wore unsaturated original SCLs and received CyA instillations 2 times daily and, also, artificial tears. Apart from a standard ophthalmic examination, the assessment included Schirmer's test, Norn's test, vital eye stain tests, tear osmometry, laser confocal tomography of the cornea, optical coherence tomography of the anterior segment with meniscometry, impression cytology of the conjunctiva, tear pH measurement, plating of the content of the conjunctival cavity, measurement of the width of the palpebral fissure, and calculation of the ocular surface disease index. Treatment results were followed up at 1, 3, 6, and 12 months., Results: The use of 0.05% CyA-saturated SCLs allows to halve treatment time for patients with severe KSC (down to 1 week - 1 month) as compared to unsaturated original SCLs in combination with 0.05% CyA instillations and to reduce it 5 times as compared to 0.05% CyA instillations only., Conclusion: The new method of KSC treatment that involves the use of medical SCL of original design (ensures even distribution of 0.05% CyA across the ocular surface) and preservative-free artificial tears has demonstrated high therapeutic effectiveness as compared to existing methods.