Combined Effect of Basic Antiherpetic Drugs with a New Inhibitor of the Terminase Complex of Herpes Simplex Virus Type 1 in Vero Cell Cultures.

Carriers of herpes simplex virus type 1 (HSV-1) account for more than 90% of the global population. Infection manifests itself in the formation of blisters and ulcers on the face or genitals and can cause blindness, encephalitis, and generalized infection. All first- and second-line modern antiherpetic drugs selectively inhibit viral DNA polymerase. The purine-benzoxazine conjugate LAS-131 ((S)-4-[6-(purin-6-yl)aminohexanoyl]-7,8-difluoro-3,4-dihydro-3-methyl-2H-[1,4]benzoxazine), which we have described earlier, uses the large subunit of the HSV-1 terminase complex as a biotarget and selectively inhibits HSV-1 reproduction in vitro. Basically new results were for the first time obtained to characterize the combined effect on human herpesvirus infection for LAS-131 used in combination with practically significant antiviral compounds, including the nucleoside analogs acyclovir (ACV), penciclovir (PCV), ganciclovir (GCV), brivudine (BVdU), iododeoxyuridine (IdU), and adenine arabinoside (Ara-A); the nucleoside phosphonate analog cidofovir (CDV); and the pyrophosphate analog foscarnet (FOS). A cytopathic effect (CPE) inhibition assay showed that the drug concentration that inhibited the virus-induced CPE by 50% decreased by a factor of 2 (an additive effect, FOS) or more (a synergistic effect; ACV, PCV, GCV, IdU, BVdU, Ara-A, and CDV) when the drugs were used in combination with LAS-131. Nonpermissive conditions for HSV-1 reproduction were thus created at lower drug concentrations, opening up new real possibilities to control human herpesvirus infection.

Lensless optical encryption with speckle-noise suppression and QR codes.

The majority of contemporary optical encryption techniques use coherent illumination and suffer from speckle-noise pollution, which severely limits their applicability even when information encoded into special "containers" such as a QR code. Spatially incoherent encryption does not have this drawback, but it suffers from reduced encryption strength due to formation of an unobscured image right on top of the encrypted one by undiffracted light from the encoding diffraction optical element (DOE) in axial configuration. We present a new lensless encryption scheme, experimentally implemented with two liquid crystal spatial light modulators, that does not have this disadvantage because of a special encoding DOE design, which forms desired light distribution in the photosensor plane under spherically diverging illumination without a converging lens. Results of optical experiments on encryption of QR codes and successful information retrieval from decoded images are presented. Conducted analysis of encryption strength demonstrates sufficiently high key sensitivity and large enough key space to resist any brute force attacks.

WAYS TO IMPROVE THE EFFICACY OF ORTHOPEDIC TREATMENT OF PATIENTS WITH SEVERE EXCESSIVE TOOTH WEAR.

Excessive tooth wear is currently one of the main problems of oral health. Excessive tooth wear affects both function and aesthetics. Teeth with excessive tooth wear cannot be effectively used for biting and chewing food. Treating excessive tooth wear is complex and time consuming. Studies on increasing the effectiveness of treatment of such patients are relevant. The study involved 60 people with a significant degree of excessive tooth wear and a decrease in the height of the bite. We examined patients using measurements of the electromyographic (EMG) activity of mm.masseter and temporalis. The subjects were divided into two groups - in the first group (30 people), the maxillofacial system was prepared for further prosthetics by wearing a removable dental splint-teethguard, in the second group (30 people) we used both removable splint-teethguards and transcutaneous electrical nerve stimulation (TENS). In both groups, an electromyographic study of mm.masseter and temporalis was performed after 1 week, 1 and 2 months of treatment. In patients with excessive tooth wear and a significant decrease in bite height, our method of preparation for orthopedic treatment contributed to a more rapid normalization of mm.masseter and temporalis functions. The results indicate a pronounced positive effect of the use of removable teeth guard and TENS on the normalization of the bioelectric activity of the masticatory muscles in the preparation of patients for orthopedic treatment of excessive tooth wear.

[Factors Affecting the Labeling of NIH 3T3 Cells with Magnetic Nanoparticles].

The factors that affect the labeling of NIH 3T3 murine fibroblasts with Fe3O4-based magnetic nanoparticles (MNPs) were studied using MNPs produced by the gas condensation and solution precipitation methods and MNPs surface-modified with 3-aminopropylsilane or L-lysine. The production method, surface modifications, the particle concentration and size, the state of the cell population, and the method of MNP introduction were found to substantially affect the efficiency of MNP binding by cells. In particular, large MNP clusters may occur in MNP suspensions in DMSO, and their disruption by sonication increased the percent yield of magnetically labeled cells. Static incubation of a cell suspension led to a more efficient labeling as compared with continuous agitation. Cells attached to a plastic support could be labeled to a higher degree than cells in suspension, but required substantially longer incubations with MNPs. MNP centrifugation on cell layers (magnetic spinoculation) significantly increased the rate and efficiency of labeling. The stability of magnetic labeling was shown to depend on the MNP dose during labeling. Electron microscopy studies demonstrated that MNPs were associated with the cell surface after 20-min incubation with cells and were mostly in the cell interior after 4-h incubation. The results of the study may be useful for preparation and application of magnetized cell samples.

[Mental disorders and cognitive impairment in patients with antiphospholipid syndrome].

Mental disorders (mainly anxiety and depressive disorders) and cognitive impairment are often found in patients with antiphospholipid syndrome (APS), but their prevalence, structure, and mechanisms of occurrence are not well researched. The review provides literature data on the frequency, spectrum and possible causes of mental disorders and cognitive impairment in patients with APS, the pathogenetic mechanisms of these disorders (in particular, the important role of antiphospholipid antibodies, stress factors, chronic inflammation), the relationship between APS, mental disorders and as well as cognitive impairment is examined. Special attention is paid to the influence of mental disorders and cognitive impairment on patients adherence to treatment, their quality of life, as well as the particularities of psychopharmacotherapy of mental disorders in patients with APS. The aim of the review is to actualize the interdisciplinary problem of mental disorders and cognitive impairment in patients with APS and the need to introduce a partnership model of care.

[Chronic pain and depression in patients with rheumatoid arthritis: results of five - year follow - up].

The aim of the study was to analyze the factors affecting chronic pain in patients with rheumatoid arthritis (RA). MATERIALS AND METHODS: 128 patients with reliable diagnosis of RA [111 (86.7%) women and 17 (13.3%) men] were examined. The mean age of patients was 47.4±11.3 years, the median duration of the disease was 96 [48; 228] months. When included in the study in most patients, the activity of RA in DAS28 was moderate (n=56; 43.7%) or high (n=48; 37.5%). BPI (Brief Pain Inventory) scale was used to determine the severity of pain and its impact on various aspects of life. The anxiety - depressive spectrum disorders (ADDs) were diagnosed by psychiatrist during a semistructured interview according to ICD-10 criteria in 123 (96.1%) patients. The severity of depression was determined by the Montgomery-Asberg depression rating scale, anxiety - by Hamilton anxiety scale. For the diagnosis of cognitive impairment used clinical and psychological techniques. Psychopharmacotherapy (PPhT) by antidepressants or anxiolytics is offered to all patients with ADDs, 52 of them agreed to treatment, 71 patients refused. The next groups selected depending on the therapy: 1st - with conventional disease - modifying antirheumatic drugs (cDMARDs; n=39), 2nd - with cDMARDs+PPhT (n=43), 3d - with cDMARDs + biologic (b) DMARDs (n=32), 4th - with cDMARD+bDMARDs+PPhT (n=9). The dynamics of ADDs and outcomes of RA in 5 years were evaluated in 83 (67.5%) patients. RESULTS: When included in the study, 94 (75.2%) patients with RA had moderate and severe pain. According to the regression analysis, the maximum intensity pain in BPImax after 5 years of follow - up associated not the only factors connected with RA - high DAS28, the serum level of C-reactive protein, the degree of radiological stage and functional insufficiency, duration of RA and a lesser duration of glucocorticoids intake, but also with continuing depressive episodes in the framework of recurrent depression and the initial presence of cognitive impairment. The severity of pain after 5 years of follow - up was higher in RA patients receiving only сDMARDs, without the use of bDMARDs and in the absence of PPhT associated with ADDs. CONCLUSION: Depressive episode within recurrent major depression is a significant factor in the chronicity of pain in patients with RA. Timely effective PPhT of depression, selected taking into account depression structure and personal characteristics of the patient, leads to a steady decrease in the severity of pain in patients with RA.

Phase-Sensitive Evidence for the Sign-Reversal s_{±} Symmetry of the Order Parameter in an Iron-Pnictide Superconductor Using Nb/Ba_{1-x}Na_{x}Fe_{2}As_{2} Josephson Junctions.

Josephson current provides a phase-sensitive tool for probing the pairing symmetry. Here we present an experimental study of high-quality Josephson junctions between a conventional s-wave superconductor Nb and a multiband iron-pnictide Ba_{1-x}Na_{x}Fe_{2}As_{2}. Junctions exhibit a large enough critical current density to preclude the d-wave symmetry of the order parameter in the pnictide. However, the I_{c}R_{n} product is very small ≃3µV, which is not consistent with the sign-preserving s_{++} symmetry either. We argue that the small I_{c}R_{n} value, along with its unusual temperature dependence, provides evidence for the sign-reversal s_{±} symmetry of the order parameter in Ba_{1-x}Na_{x}Fe_{2}As_{2}. We conclude that it is the phase sensitivity of our junctions that leads to an almost complete (below a subpercent) cancellation of supercurrents from sign-reversal bands in the pnictide.

A Technique for In Vitro Studying of the Permeability of the Spinal Cord Dura Mater.

We propose an in vitro method for studying permeability of spinal cord dura mater for components of autological serum using an original device. Sixty native samples of the spinal cord dura mater obtained from 12 mongrel dogs were used for testing of the device. The coefficient of permeability variation (V) for blood serum substances did not exceed 5% in most cases excluding lactate (V=8.03%). Analysis of spinal cord dura mater permeability in vitro for various substances using the developed device provides reproducible results with acceptable variability (5-10%).

Comparative analysis of anxiety-depressive spectrum disorders in patients with rheumatic diseases.

AIM: Research objective - comparative analysis of incidence and structure of anxiety-depressive spectrum disorders (ADD) in patients with various rheumatic diseases (RD). MATERIALS AND METHODS: 613 patients with RD were enrolled in the study: 180 with a reliable diagnosis of systemic lupus erythematosus (SLE), 128 with rheumatoid arthritis (RA), 110 with systemic sclerosis (SSc), 115 with Behcet's disease (BD), 80 with primary Sjögren's syndrome (pSS). Female prevailed in all groups (95% of patients with pSS, 88,2% - SSc, 87,2% - RA, 85,5% of SLE) except BD patients (70% male). The mean age was 42.3±1.54 years and was lower in patients with BD (33.3±0.98 years) and SLE (34.6±0.93 years) compared to patients with SSc (49.9±2.47 years), RA (47.4±0.99 years) and pSS (46.2±2.3 years). The mean RD duration was 130,0±8,65 months and was more at BD - 148,5±10,4 months, pSS - 141,6±8,92 months, RA - 138,4±10,1months, and less at SLE - 134,9±8,8 months and SSc - 87,0±5,04 months. The mean SLE activity index SLEDAI was 9,13±0,63 points (high), RA (DAS28) - 5,26±0,17 points (high), BD (BDCAF) - 3,79±0,2 points (moderate) and SSc by G. Valentini - 1,1±0,20 points (moderate). Glucocorticoids took 100% of patients with pSS, 91,1% - SLE, 90% - SSc, 87% - BD and 67,2% - RA patients; conventional disease modifying anti-rheumatic drugs (cDMARDs) took 90% of patients with SSc, 84% - BD, 79,6% - RA, 68% - pSS, 40,6% - SLE. Biologic DMARDs took 32% of patients with RA, 17,4% - BD, 7,3% - SSc and 7,2% - SLE. Mental disorders were diagnosed by psychiatrist as a result of screening by the hospital anxiety and depression scale (HADS) and in semi-structured interview in accordance with the ICD-10/ DSM-IV. The severity of depression was evaluated by Montgomery-Asberg Depression Rating Scale (MADRS) and anxiety - by Hamilton Anxiety Rating Scale (HAM-A). Projective psychological methods were used for cognitive impairment detection. RESULTS: Screening of depressive disorders (HADS-D≥8) was positive in 180 (29,4%) patients with RD, including 74 (41%) patients with SLE, 38 (35%) - SSc, 29 (23%) - RA, 23 (20%) - BD and 16 (20%) - pSS; anxiety disorders (HADS-A≥8) - in 272 (44,4%) patients, including 66 (52%) patients with RA, 40 (50%) - pSS, 77 (43%) - SLE, 45 (41%) - SSc and 44 (38%) - BD. In accordance with the ICD-10/ DSM-IV depressive disorders have been identified in 389 (63%) patients, including 94 (73%) patients with RA, 71 (64,5%) - SSc, 69 (60%) - BD, 90 (50%) - SLE and 39 (49%) - pSS; anxiety disorders - in 377 (61,5%) patients, including 20 (25%) patients with pSS, 44 (24,5%) - SLE, 29 (23%) - RA, 20 (17%) - BD and 7 (6,4%) - SSc. CONCLUSION: Anxiety-depressive spectrum disorders are typical for most patients with RA, SLE, SSc, pSS and BD. ADDs diagnosis in RD patients with the use of the HADS did not reveal a significant proportion. To obtain objective data on the frequency and structure of ADDs, psychopathological and clinical psychological diagnosis is necessary.

Sequence of Quantum Phase Transitions in Bi2Sr2CaCu2O(8+δ) Cuprates Revealed by In Situ Electrical Doping of One and the Same Sample.

Our recently discovered electrical doping technique allows a broad-range variation of carrier concentration without changing the chemical composition. We show that it is possible to induce superconductivity in a nondoped insulating sample and to tune it reversibly all the way to an overdoped metallic state. This way, we can investigate the whole doping diagram of one and the same sample. Our study reveals two distinct critical points. The one at the overdoped side is associated with the onset of the pseudogap and with the metal-to-insulator transition in the c-axis transport. The other at optimal doping is associated with the appearance of a "dressed" electron energy. Our study confirms the existence of multiple phase transitions under the superconducting dome in cuprates.

[The synthesis of RGD peptide derivatives containing glutaric and adipic residues].

A method of the synthesis of RGD peptide derivatives containing glutaric or adipic residues linked with α-amino group of L-arginine and allowing carrying out their coupling with other biomolecules and nanoparticles.

Blood circulation in muscles of the back in scoliosis deformity of the lumbar spine and under conditions of its correction.

Experiments performed on dogs showed that the formation of scoliotic deformity of the lumbar spine sharply affects the hemodynamics of the back muscles, which manifested in asymmetric arterial blood fl ow, increased blood supply to the tissues, and impaired venous outflow. The changes were more pronounced on the apex of epy developing deformity. Correction of scoliotic deformity gradually restored blood circulation in muscles of the back. The use of methods of functional diagnostic for evaluation of the status of blood circulation in the tissues of the back has diagnostic value and allows evaluation of the treatment efficiency.

[Stimulation of pelvic fracture healing by local injection of autologous plasma in combination with metabolically active substances that have an antioxidant and antihypoxic effect].

AIM: The study was aimed at performing an experimental trial of the reparative osteogenesis stimulation by local injection of autologous plasma in combination with metabolically active substances such as L-ascorbic acid and D-glucose for management of pelvic fractures. MATERIAL AND METHODS: The experiment was carried out on twenty-six mongrel dog of both sexes aged 1.5 ± 0.09 years and with body weight of 17 ± 0.5kg. Transverse osteotomy was performed in the acetabulum (n = 20) and in the ilium body (n = 6). The fractures were stabilized with external fixators. On days two through 5 after the operation all dogs had intraarticular or intraosseous injections of the saline solution throughout 24 hours in the dose of 0.4 ml per day. Experimental animals were additionally injected once a day with 1 ml of a composition consisting of the ascorbic acid and glucose. The external apparatuses were dismounted on day 21 after the operation. The animals for histological study were euthanized on day 14 and 42 after the operation. The study used radiographic and histological methods of study as well as the method of radiographic electron probe microanalysis. RESULTS: The control animals that had either intraosseous or intraarticular saline injections alone had fibro-cartilaginous union of the pelvic fragments. They developed bone deformity due to secondary displacement upon apparatus removal. The experimental animals had primary bone union on day 14. The bone was consolidated after the removal of the apparatus. CONCLUSION: Autologous blood plasma in combination with active substances of ascorbic acid and glucose had a marked stimulating effect on pelvic fracture healing if applied locally in the posttraumatic period. The method of reparative osteogenesis stimulation that was developed is low traumatic. It does not hinder early functional loading and allows control of reparative process basing on the biological principles of tissue regeneration.

[Clinical and pathogenetic relationships between immuno-inflammatory rheumatic diseases and psychic disorders].

Literature data and original observations have been used to develop the rationale for the necessity of studying psychic disorders (PD) in patients with immuno-inflammatory rheumatic diseases (RD), such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Special attention is given to the high frequency of disturbances of the anxiety and depression profile (DADP) in patients having RA and SLE with reference to the common provoking stress and pathogenic factors, clinical manifestations, and RD. Great importance is attributed to the degree of depression associated with inflammatory activity, pain intensity, fatigue, sleep disorders, severe functional insufficiency and low quality of life in the patients with RA and SLE. Special emphasis is laid on the influence of depression and stress factors on the survival and morality of patients with these pathologies, the necessity of their combined treatment with the participation of rheumatologists, psychiatrists and medical psychologists for the improvement of clinical course and prognosis of RD.

Evidence for nonlocal electrodynamics in planar Josephson junctions.

We study the temperature dependence of the critical current modulation I(c)(H) for two types of planar Josephson junctions: a low-Tc Nb/CuNi/Nb and a high-Tc YBa2Cu3O(7-δ) bicrystal grain-boundary junction. At low T both junctions exhibit a conventional behavior, described by the local sine-Gordon equation. However, at elevated T the behavior becomes qualitatively different: the I(c)(H) modulation field ΔH becomes almost T independent and neither ΔH nor the critical field for the penetration of Josephson vortices vanish at Tc. Such an unusual behavior is in good agreement with theoretical predictions for junctions with nonlocal electrodynamics. We extract absolute values of the London penetration depth λ from our data and show that a crossover from local to nonlocal electrodynamics occurs with increasing T when λ(T) becomes larger than the electrode thickness.

[The magnitude of fatigue and its association with depression, pain, and inflammatory activity in rheumatoid arthritis].

AIM: To analyze the rate of clinically significant fatigue and to search for its predictors in patients with rheumatoid arthritis (RA). SUBJECTS AND METHODS: The investigation included 95 patients with a valid RA diagnosis. The majority of the patients were women (87.4%); mean age was 46.7 +/- 1.2 years; mean disease duration was 135.5 +/- 11.6 months. The authors evaluated RA activity by the Disease Activity Score (DAS28), magnitude of fatigue by the Fatigue Severity Scale (FSS), that of pain by the Brief Pain Inventory, and functional status and quality of life by the Health Assessment Questionnaire and EQ-5D. A psychiatrist diagnosed mental disorders in accordance with ICD-10 and using the psychiatric and psychological scales and procedures. RESULTS: 80% of the patients felt clinically significant fatigue (FSS scores of > or = 4). Multivariate analysis yielded a prognostic model that made it possible to state that clinically significant fatigue was primarily associated with the magnitude of depression by the Hospital Anxiety and Depression Scale, the presence of a depressive episode, the duration of anxiety and depressive spectrum, the magnitude of pain (Ritchie index), DAS28, and the presence of osteoporosis. CONCLUSION: The presence and magnitude of depression along with the magnitude of pain are an important factor that influences the formation of fatigue in RA, which gives rise to evident functional failure and a low quality of life. Combination therapy for RA may be effective when mental disorders, mainly the anxiety and depressive spectrum, are timely diagnosed.

[Blood circulation features by treatment of multiply mandible fractures by means of transosseus osteosynthesis].

The multiple injury of the mandible was modeled experimentally in 27 adult mongrel dogs with subsequent fixation using a device for transosseous osteosynthesis. The special features of soft tissue hemodynamics in the injury zone and contralateral symmetrical part were studied. It has been determined that the unidirectional changes in functional properties of the arterial bed vessels occur under the conditions created, and these changes are more marked on the injury side and characterized by vasodilatation. Circulation in the injury zone doesn't recover by the end of fixation. Performing the measures directed for the improvement of vascular elastotonic properties during mandibular fracture treatment will allow to decrease the degree of hemodynamics disorders in paraosseous tissues, as well as will have a positive effect on a final clinical outcome.

[Psychosocial pathomorphosis of depressions]. / Psikhosotsial'nyi patomorfoz depressii.

OBJECTIVE: The aim is to determine the changes in phenomenology of depressions (mostly of melancholic type with pronounced affect of sadness, chronobiological shift, neurovegetative changes and typical affect-congruent depressive ideas) over the past decades. MATERIAL AND METHODS: We've compared the archival data of one of the authors (V.N.K.) obtained in the study of depression within 1980-1086 years (1st group, 103 patients, 47 with recurrent depression and 56 with bipolar depression) and the data of the study of depression during 2015-2021 years with registration of symptoms with the same psychopathological scale at the same clinic for affective disorders (2nd group, 109 patients, 52 with recurrent depression and 57 with bipolar depression). The groups are age-comparable (21-59 y.o.). The Hamilton Depression Rating Scale (HDRS-17) has been used to assess the severity of depression (score of 21-32 in both groups). Statistics included frequency analysis with use of χ2 criterion. RESULTS: Biologically mediated symptoms (shortened sleep with early awakening, typical diurnal variations with vitalization of depressive affect and loss of energy mostly first half of day, decreased appetite, libido and motivation for any activity) were not statistically different in the study groups. Whereas symptoms associated with emotional reactivity and congruent depressive ideations like worthlessness, guilt, suicidal thoughts, as well as anaesthesia psychica dolorosa - were statistically rare in 2nd group, except anhedonia. The same time the facts which have been obvious amongst patients of 2nd group were the difficulties to verbalize their feelings, shortage of vocabular for reflections about their suffering, especially amongst young patients. CONCLUSION: The results of the study can indicate some changes in the phenomenology of depression over the past decades. Basically, the same underlying disorders can produce different clinical presentation, particularly concerning an awareness and verbalization of moral feelings and other emotions. One of the possible psycholinguistic assumption may be limited vocabulary for feelings because of spreading social networks with very poor and formal language instead of live direct communication.

[Steadfastly increased level of the ciliary neurotrophic factor in the blood serum within the positive therapeutic dynamics of depression as possible prognostic marker of depressive relapse]. / Ustoichivoe povyshenie urovnya tsiliarnogo neirotroficheskogo faktora v syvorotke krovi pri polozhitel'noi terapevticheskoi dinamike depressii kak veroyatnyi prognosticheskii marker retsidiva depressivnogo epizoda.

OBJECTIVE: To study a role of the ciliary neurotrophic factor (CNTF) in the pathogenesis of depression and its prognostic significance in dynamics of the antidepressant therapy. MATERIAL AND METHODS: CNTF level was investigated in the blood serum of patients with melancholic depression (n=32) before the start of therapy and after 30 days, when improvement was achieved by at least 75% of baseline scores on the Hamilton Depression Rating Scale. RESULTS: Steadfastly increased level of CNTF in the blood serum of patients with melancholic depression compared with the control, remaining practically unchanged with an obvious improvement in the condition - 732.2±126.5 and 679.1±63.1 pg/ml of serum, respectively (p>0.05). CONCLUSION: The initially elevated level of CNTP indicates its probable significance in the pathogenesis of depression; persistently high serum CNTP level, despite clinical improvement during therapy, can serve as a predictor of the stability of the biological mechanisms of recurrent depressive disorder with a continuing risk of another relapse of a depressive episode.

[Mandible reparative regeneration and adaptive remodeling by multiply fracture treatment by means of transbone osteosynthesis].

Mandibular injuries are the most common pathology of the facial skeleton. The aim of the study was to substantiate the effectiveness of treatment of this pathology using transosseous osteosynthesis method from the experimental and morphological point of view. The bone union of mandibular fragments has been confirmed experimentally in 27 adult mongrel dogs after a month of fixation by the device and within a month after its demounting. The functionally adequate fibrous and connective union has been formed in the zone of mandibular junction rupture in the same periods.